Retrospective evaluation of the effect of carotid artery stenosis on cerebral oxygen saturation during off-pump coronary artery bypasses grafting in adult patients.

BACKGROUND: It is unknown whether cerebral oxygenation in patients with carotid artery stenosis (CAS) undergoing off-pump coronary artery bypass grafting (CABG) differs from that in patients without CAS. Thus, the effect of the presence of CAS ≥ 50 % on cerebral oxygenation during off-pump CABG in adult patients was evaluated retrospectively. METHODS: Eleven patients with CAS ≥ 50% and 14 patients without CAS ≥ 50% were enrolled. Regional cerebral tissue oxygen saturation (rSO2) was quantified using near-infrared spectroscopy. Mean arterial pressure, cardiac index, central venous pressure (CVP), and rSO2 at specific points were collected, and significant changes in each parameter were detected using repeated analysis of variance. Mean rSO2 and minimum rSO2 during anastomosis were analyzed by one-way analysis of variance. Multiple logistic regression analysis was used to estimate the odds ratio (OR) with 95% confidence interval (CI) for cerebral desaturation (a decrease in rSO2 ≥ 10% from preoperative value). RESULTS: Two patients with CAS ≥ 50% who received complete carotid artery stenting preoperatively were excluded from the analyses. In both patients with and without CAS, a decrease in rSO2 and cardiac index and an increase in CVP were observed during anastomosis. Mean (SD) maximum decrease in rSO2 from preoperative value was 9.2 (12.7) % on the left side and 8.1 (11.7) % on the right side in patients with CAS ≥ 50%, and 13.5 (11.3) % on the left side and 16.1 (9.8) % on the right side in patients without CAS ≥ 50% (p = 0.316). Neurological complications were not identified in both patients with and without CAS ≥ 50%. In multiple logistic regression analysis, CAS ≥ 50% was not associated with an increased risk of cerebral desaturation (OR 0.160, 95% CI 0.036-0.707, p = 0.016), and rSO2 decreased with decreasing cardiac index < 2.0 l/min/m(2) (OR 3.287, 95 % CI 2.218-5.076, p < 0.001). CONCLUSIONS: CAS ≥ 50% was not an independent risk factor of cerebral desaturation during off-pump CABG. Our results suggest that maintaining cardiac output can prevent a decrease in cerebral oxygenation in both patients with and without CAS ≥ 50%.

Phase I/II trial of definitive carbon ion radiotherapy for prostate cancer: evaluation of shortening of treatment period to 3 weeks.

BACKGROUND: The purpose of this study was to evaluate the feasibility of a new shortened 3-week treatment schedule of carbon ion radiotherapy (CIRT) for prostate cancer. METHODS: Beginning in May 2010, patients with T1b-T3bN0M0, histologically proven prostate adenocarcinoma were enrolled in the phase II trial of CIRT. Patients received 51.6 GyE in 12 fractions over 3 weeks (protocol 1002). The primary end point was defined as the incidence of late adverse events that were evaluated based on the Common Terminology Criteria for Adverse Events version 4.0. Biochemical failure was determined using the Phoenix definition (nadir +2.0 ng ml(-1)). RESULTS: Forty-six patients were enrolled, and all patients were included in the analysis. The number of low-, intermediate-, and high-risk patients was 12 (26%), 9 (20%), and 25 (54%), respectively. The median follow-up period of surviving patients was 32.3 months. Two patients had intercurrent death without recurrence, and the remaining 44 patients were alive at the time of this analysis. In the analysis of late toxicities, grade 1 (G1) rectal haemorrhage was observed in 3 (7%) patients. The incidence of G1 haematuria was observed in 6 (13%) patients, and G1 urinary frequency was observed in 17 (37%) patients. No ⩾G2 late toxicities were observed. In the analysis of acute toxicities, 2 (4%) patients showed G2 urinary frequency, and no other G2 acute toxicities were observed. CONCLUSIONS: The new shortened CIRT schedule over 3 weeks was considered as feasible. The analysis of long-term outcome is warranted.

Perfusion index derived from a pulse oximeter can predict the incidence of hypotension during spinal anaesthesia for Caesarean delivery.

BACKGROUND: Hypotension during spinal anaesthesia for Caesarean delivery is a result of decreased vascular resistance due to sympathetic blockade and decreased cardiac output due to blood pooling in blocked areas of the body. Change in baseline peripheral vascular tone due to pregnancy may affect the degree of such hypotension. The perfusion index (PI) derived from a pulse oximeter has been used for assessing peripheral perfusion dynamics due to changes in peripheral vascular tone. The aim of this study was to examine whether baseline PI could predict the incidence of spinal anaesthesia-induced hypotension during Caesarean delivery. METHODS: Parturients undergoing elective Caesarean delivery under spinal anaesthesia with hyperbaric bupivacaine 10 mg and fentanyl 20 µg were enrolled in this prospective study. The correlation between baseline PI and the degree of hypotension during spinal anaesthesia and also the predictability of spinal anaesthesia-induced hypotension during Caesarean delivery by PI were investigated. RESULTS: Baseline PI correlated with the degree of decreases in systolic and mean arterial pressure (r=0.664, P<0.0001 and r=0.491, P=0.0029, respectively). The cut-off PI value of 3.5 identified parturients at risk for spinal anaesthesia-induced hypotension with a sensitivity of 81% and a specificity of 86% (P<0.001). The change of PI in parturients with baseline PI ≤ 3.5 was not significant during the observational period, while PI in parturients with baseline PI>3.5 demonstrated marked decreases after spinal injection. CONCLUSIONS: We demonstrated that higher baseline PI was associated with profound hypotension and that baseline PI could predict the incidence of spinal anaesthesia-induced hypotension during Caesarean delivery.

Massive macroglossia developing fast and immediately after endotracheal extubation.

We report an unusual case of massive macroglossia that developed very rapidly after neurosurgery in the park bench position with neck flexion. A few minutes after endotracheal extubation, massive macroglossia was noticed with marked protrusion of the tongue from the oral cavity. The patient's hospital stay was prolonged due to difficulty in speaking and eating. Macroglossia is a rare complication; however, it may cause life-threatening airway obstruction. It is important to be prepared for managing post-operative macroglossia and keep in mind that it may develop rapidly, especially after prolonged surgery performed with sustained neck flexion. The patient should be informed of the risk of macroglossia and the associated problems prior to the operation.

Neutron-induced signal on the single crystal chemical vapor deposition diamond-based neutral particle analyzer.

A diamond-based neutral particle analyzer (DNPA) array composed of single-crystal chemical vapor deposition (sCVD) diamond detectors was installed on the Large Helical Device (LHD) for measuring the helically trapped energetic particles. In high neutron flux experiments, the unwanted neutron-induced pulse counting rate should be estimated using the neutron diagnostics because a diamond detector is sensitive to neutrons as well as energetic neutral particles. In order to evaluate the quantitative neutron-induced pulse counting rate on the DNPA, the response functions of the sCVD diamond detector for mono-energetic neutrons were obtained using accelerator-based D-D and D-7Li neutron sources in Fast Neutron Laboratory (FNL). As a result of the neutron flux estimation by the Monte Carlo N-Particle code at the NPA position in the LHD and the response function obtained in the FNL experiment, the counting rate of the neutron-induced signal was predicted to be 1.1 kcps for the source neutron emission rate of Sn = 1 × 1015 n/s. In the LHD experiment, the neutron-induced signals were observed by closing the gate valve during the plasma discharges. It is found that the counting rates of the neutron-induced signals proportional to Sn reached 1.1 kcps at Sn = 1 × 1015 n/s. As a result of the quantitative estimation of the neutron-induced signals on the DNPA using other neutron measurements, it has become possible to accurately measure energetic neutral particles in the high neutron flux experiment.

Functional alterations in beta'-actin from a KB cell mutant resistant to cytochalasin B.

We recently described the isolation of mutant KB cells (Cyt 1 cells) resistant to the cytotoxic effect of cytochalasin B (CB). This mutant carried an altered beta-actin; i.e., beta'-actin (Toyama, S., and S. Toyama. 1984. Cell. 37:609-614). In the present study, we have examined the functional properties of actin in Cyt 1 cells. Our results showed that increased resistance of Cyt 1 cells to CB was reflected in altered properties of beta'-actin itself. This was shown directly by two findings. First, the polymerization of beta'-actin was more resistant than that of beta- or gamma-actin to the multiple effects of CB. Second, beta'-actin bound less CB than beta- or gamma-actin. The functional alteration of beta'-actin in Cyt 1 cells was further supported by the observation that, although treatment of KB cells with CB increased the pool of unpolymerized actin, the same treatment did not affect the pool of unpolymerized actin in Cyt 1 cells, and that microfilaments of Cyt 1 cells were more resistant to the disrupting action of CB than those of KB cells. These results strongly suggest that the primary site of action of CB on cell motility processes is actin.

Direct proof that the primary site of action of cytochalasin on cell motility processes is actin.

We have previously described the isolation of a mutant KB cell (Cyt 1 mutant) resistant to the cytotoxic effect of cytochalasin B (CB). The Cyt 1 mutant carries an altered form of beta-actin (beta'-actin) and lacks normal beta-actin (Toyama, S., and S. Toyama. 1984. Cell. 37:609-614). Increased resistance of the Cyt 1 mutant to CB in vivo is reflected in altered properties of beta'-actin in vitro (Toyama, S., and S. Toyama. 1988. J. Cell Biol. 107:1499-1504). Here, we show that the mutation in beta-actin is solely responsible for the cytochalasin-resistant phenotype of the Cyt mutant. We have isolated a cDNA clone encoding beta'-actin from Cyt 1 cells. Sequence analysis reveals two mutations in the coding region that substitute two amino acid residues (Val139----Met and Ala295----Asp). Expression of the beta'-actin cDNA confers cytochalasin resistance upon transformed cytochalasin-sensitive KB cells. Levels of resistance to CB in the transformed cell clones correlate well with amounts of beta'-actin polypeptide. Both of the two mutations in beta'-actin are necessary for the high level expression of cytochalasin resistance. Overall, we conclude that the primary site of action of cytochalasin on cell motility processes in vivo is actin.

Interference with the endosomal acidification by a monoclonal antibody directed toward the 116 (100)-kD subunit of the vacuolar type proton pump.

A monoclonal antibody (OSW2) was prepared by using human osteosarcoma cells. OSW2 was found to be directed toward the 116 (also called 100)- kD protein that uniquely associates to the vacuolar-type proton pump. The antibody specifically localized acidic membrane compartments that could be visualized with acridine orange in many types of human cells. It also reacted with the surface and was internalized along the endosomal pathway. Monitoring the endosome pH by using FITC-dextran and acridine orange suggested that the antibody interfered with low pH. Cell-free experiments indicated that the ATP-dependent acidification was inhibited in endosomes associated with OSW2. In contrast, the antibody gave little effect on the ATPase activity of the solubilized H+ pump. The internalization of OSW2 reduced infectivity of certain enveloped viruses (influenza, SFV, VSV) by 50 to 80%. Inhibition of viral fusion was directly demonstrated by monitoring the fate of octadecylrhodamine-labeled influenza virus fluorescence. These results indicate that the 116 (100)-kD protein is necessary for the control of pH. The antibody represents a novel probe for understanding the role of the endosomal compartments in cellular physiology.

[Aortic valve replacement through right thoracotomy; report of a case].

A 78-year-old female was admitted to our hospital with a diagnosis of severe aortic valve regurgitation. She had had dyspnea on effort and syncope twice in 5 months. She had also suffered from right pneumonia 8 years before, and her respiratory function was severely constrictive. Chest X-ray showed her mediastinum significantly shifted toward the right side. Chest computed tomography (CT) revealed the main pulmonary artery, right atrium (RA) and right pulmonary veins also shifted toward the right. We planned right thoracotomy at 4th intercostals space to obtain a good surgical field. A cardiopulmonary bypass was established by RA appendage drainage and femoral artery perfusion. Aortic valve replacement(AVR) was performed successfully after aortic clamp. Though defibrillator pads were placed on her back and the anterior wall of the left chest during operation, no ventricular fibrillation occurred. AVR via right thoracotomy is considered to be a good option for such a mediastinum shifted case.

[Aortic root replacement for aortic dissection and aortic regurgitation due to aortitis syndrome].

Aortic aneurysms and aortic regurgitation (AR) with aortitis syndrome are occasionally reported in young women. We report a case of aortic dissection with severe AR in an 8-year-old girl. The patient underwent aortic root replacement with a composite graft. Pathological report revealed aortitis syndrome and steroid therapy was continued to suppress further inflammatory vascular reaction.

Pharmacokinetics of internally labeled monoclonal antibodies as a gold standard: comparison of biodistribution of 75Se-, 111In-, and 125I-labeled monoclonal antibodies in osteogenic sarcoma xenografts in nude mice.

In order to know the true biodistribution of anti-tumor monoclonal antibodies, three monoclonal antibodies (OST6, OST7, and OST15) against human osteosarcoma and control antibody were internally labeled with 75Se by incubating [75Se]methionine and hybridoma cells. 75Se-labeled monoclonal antibodies were evaluated both in vitro and in vivo using the human osteogenic sarcoma cell line KT005, and the results were compared with those of 125I- and 111In-labeled antibodies. 75Se-, 125I- and 111In-labeled monoclonal antibodies had identical binding activities to KT005 cells, and the immunoreactivity was in the decreasing order of OST6, OST7, and OST15. On the contrary, in vivo tumor uptake (% injected dose/g) of 75Se- and 125I-labeled antibodies assessed using nude mice bearing human osteosarcoma KT005 was in the order of OST7, OST6, and OST15. In the case of 111In, the order was OST6, OST7, and OST15. High liver uptake was similarly seen with 75Se- and 111In-labeled antibodies, whereas 125I-labeled antibodies showed the lowest tumor and liver uptake. These data indicate that tumor targeting of antibody conjugates are not always predictable from cell binding studies due to the difference of blood clearance of labeled antibodies. Furthermore, biodistribution of both 111In- and 125I-labeled antibodies are not identical with internally labeled antibody. Admitting that internally labeled antibody is a "gold standard" of biodistribution of monoclonal antibody, high liver uptake of 111In-radiolabeled antibodies may be inherent to antibodies. Little, if any, increase in tumor-to-normal tissue ratios of antibody conjugates will be expected compared to those of 111In-labeled antibodies if stably coupled conjugates are administered i.v.

Detection of human osteosarcoma-associated antigen(s) by monoclonal antibodies.

Hybrid cell lines have been derived from a fusion between mouse myeloma cells, NS1, and spleen cells from mice immunized with freshly resected osteosarcoma cells from an untreated patient. Of the 276 hybrids obtained, five secreted antibodies which bound to osteosarcoma tissues but not to autologous skin fibroblasts. The antibodies from three of these five hybrids, OST6, OST7, and OST15, reacted with all of five osteosarcoma tissues and with one chondrosarcoma tissue but not with other malignant or benign tumors. Tests of various normal tissues were negative, except for weak binding to a subpopulation of chondrocytes in articular cartilage. The reciprocal binding inhibition test showed that OST6, OST7, and OST15 antibodies were directed against different antigenic determinants.

In vivo radiolocalization of antiosteogenic sarcoma monoclonal antibodies in osteogenic sarcoma xenografts.

Monoclonal antibodies Ost6 and Ost7 (mouse Immunoglobulin G1) to human osteogenic sarcoma were isolated from ascitic fluid and labeled with radioiodine. After injection into athymic nu/nu mice with s.c. xenografts of human osteogenic sarcoma, the uptake of radioactivity in tumors, visceral organs, and blood was determined. Five days after injection, Ost6 and Ost7 showed preferential accumulation in tumors (tumor:blood ratio, 4.3). Furthermore, with testicular and bladder tumors, both unreactive with Ost7, there was no localization of radiolabeled Ost7 in xenograft growths. When Ost7 was labeled with 131I, its accumulation into human osteogenic sarcoma could be clearly visualized by whole-body gamma-scintigraphy without computer-assisted data processing.

Properties of taurine: alpha-ketoglutarate aminotransferase of Achromobacter superficialis. Inactivation and reactivation of enzyme.

The activity of taurine: alpha-ketoglutarate aminotransferase (taurine: 2-oxoglutarate aminotransferase, EC 2.6.1.55) from Achromobacter superficialis is significantly diminished by treatment of the enzyme with (NH4)2SO4 in the course of purification, and recovered by incubation with pyridoxal phosphate at high temperatures such as 60 degrees C. The inactive form of enzyme absorbing at 280 and 345 nm contains 3 mol of pyridoxal phosphate per mol. The activated enzyme contains additional 1 mol of pyridoxal phosphate with a maximum at 430 nm. This peak is shifted to about 400 nm as a shoulder by dialysis of the enzyme, but the activity is not influenced. The inactive form is regarded as a partially resolved form, i.e. a semiapoenzyme. The enzyme catalyzes transamination of various omega-amino aicds with alpha-ketoglutarate, which is the exclusive amino acceptor. Hypotaurine, DL-beta-aminoisobutyrate, beta-alanine and taurine are the preferred amino donors. The apparent Michaelis constants are as follows; taurine 12 mM, hypotaurine 16 mM, DL-beta-aminoisobutyrate 11 mM, beta-alanine 17 mM, alpha ketoglutarate 11 mM and pyridoxal phosphate 5 micron.

Interaction between Sendai virus and KB cell lines with altered cell fusion ability: a study employing electron spin resonance.

The nature of the interaction between Sendai virus and Sil mutant cells was examined by measuring a change in ESR spectrum of spin-labeled phosphatidylcholine molecules on the viral envelope. When spin-labeled virus was incubated with the Sil cells that had a reduced ability to respond to virus-induced cell fusion, interchange of the phospholipid molecules between viral envelope and cell surface membrane occurred to a smaller extent than that observed with parental cells. Moreover, the degree of the interchanging correlated with the degree of the fusion capacity of the mutant lines. The results show that the mutant cells carry such a lesion(s) on their surface membranes that the viral envelopes can hardly fuse into them.