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We performed a multicenter, an early phase II clinical trial to evaluate the feasibility, safety and efficacy of myeloablative therapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT) for the treatment of acute myelogenous leukemia (AML) in first remission. A total of 105 patients were enrolled in the study, and 56 patients in first complete remission received auto-PBSCT. The median age was 44 years. Of the 56 patients, 34 (60.7%) had M2 or M3 AML by the French-American-British Classification system. The median concentration of infused CD34+ cells was 2.3 x 10(6)/kg by recipient body weight. Median days to reach an absolute neutrophil count500/microliter and a platelet count20000/microliter were 14 and 16, respectively. The median disease-free survival rate was estimated to be 62.0% at a median follow-up time of 534 days. Although the study enrolled a small number of patients and the follow-up period was relatively short, the preliminary results were encouraging and indicated that myeloablative chemotherapy with auto-PBSCT is feasible and can be performed safely as a post-remission therapy for AML. A prospective randomized clinical trial of auto-PBSCT versus standard chemotherapy alone will be necessary to assess the efficacy of high-dose therapy facilitated by auto-PBSCT as a post-remission therapy for AML.

The 150 male patients exposed to Thorotrast who were confirmed by a 1975-1978 national survey with diagnostic X rays of 50,860 war-wounded soldiers were followed up between 1979 and 1998 (Aichi series or second series). Age-adjusted rate ratios of deaths from all causes were 3.0 times higher in Thorotrast patients compared to controls; this was statistically significant. Rate ratios for liver cancer, liver cirrhosis and leukemia were 35.0, 7.5 and 18.2, respectively.

Updated data from two series in a cancer mortality study for a total of 412 Japanese Thorotrast patients were combined. The rate ratio for all deaths of Thorotrast patients, compared to controls, started to increase after a latent period of 20 years after injection of Thorotrast. Rate ratios for liver cancer, liver cirrhosis, leukemia and lung cancer were 35.9, 6.9, 12.5 and 2.0 times higher, respectively, than those for controls.

In Fukuoka Prefecture, in south-western Japan, a regional screening program for osteoporosis was conducted from 1994 to 1995. The screening level in the bone mineral density (BMD) at the distal non-dominant radius was equal to or less than two standard deviations below age-specific mean (or = -2.0 SD). In 1177 examinees with natural menopause (mean age: 61.4, range: 42-88), 56 of those who were screened were subsequently radiologically confirmed by orthopedic specialists to have osteoporosis (case group). They were then compared with 802 normal BMD (or =-1.0 SD) women (reference group) with their lifestyle and reproductive characteristics. The adjusted odds ratio (OR) and its 95% confidence interval (CI) were calculated using a logistic regression model. A significant increase in the ORs for osteoporosis based on the number of years since menopause was observed for 7-13 years since menopause (OR = 2.3; 95% CI: 1.0-5.4) compared with7 years, however, no increasing trend in risk was evident in 14+ years since menopause (OR = 1.4; 95% CI: 0.4-5.1). Thus, the elevated risk continued up to around 10 years since menopause. These findings are consistent with previous studies that reported an alternation in the calcium metabolism and bone loss related to the length of time after menopause. Both the childhood and current milk consumption were also associated with a decreased risk: ORs were 0.4 (95% CI: 0.2-0.9) and 0.5 (95% CI: 0.3-1.0), respectively.

Myocardial stunning is characterized by the impairment of excitation-contraction coupling via a decrease in myofilament Ca2+ responsiveness, thought to be triggered by hydroxyl radicals (*OH) generated upon reperfusion. Since peroxynitrite is also expected to be produced during reperfusion, we examined whether it can induce a stunned myocardium-like impairment of cardiac myocytes. Its effect on cultured cardiac myocytes was compared with that of hydrogen peroxide (H2O2), *OH source. Infusion of peroxynitrite (0.2 mM) induced a decrease in cell motion and a complete arrest in diastole at 2.9 +/- 0.3 min, which coincided with an elevation in [Ca2+]i. Arrest induced by infusion of H2O2 (10 mM) was not associated with an increase in [Ca2+]i. The ATP content was unaffected by peroxynitrite (control, 34.3 +/- 3.4: + peroxynitrite, 32.9 +/- 3.5 nmol/mg protein) and the cells remained viable. Sulfhydryl (SH) content was decreased by peroxynitrite, but not by H2O2. The membrane fluidity (a measure of peroxidation of the membrane lipids) was not affected by peroxynitrite, but was decreased by H2O2. Onset time of arrest was unaffected by deferoxamine (0.2 mM), but was delayed by DTT (10 mM) (from 2.9 +/- 0.3 to 19.2 +/- 1.6 min). Nitrotyrosine content was unchanged by peroxynitrite, and its augmentation with Fe3+/EDTA (1 mM) was not associated with a shortened onset time of arrest. The function of the Na+/Ca2+ exchanger was impaired by peroxynitrite, but not by H2O2. Peroxynitrite and H2O2 each induce arrest, but only the former increases [Ca2+]i. One of the mechanisms of the increase in [Ca2+]i is Na/Ca2+ exchanger dysfunction. The impairments were induced through SH oxidation by peroxynitrite, but through lipid peroxidation by H2O2. Myocardial stunning may be induced by both species in concert.

A cross-sectional study on the association between the results of blood test and the blood concentration of PCB was conducted on the chronic Yusho patients. The subjects were 265 Yusho patients (134 men and 131 women) who received the annual nationwide health examination for Yusho in 1993. The results of the blood test and questionnaire survey at the annual health examination were used for the analyses using ANCOVA. Serum levels of triglycerides, total cholesterol, GOT, GPT, gamma-GTP, total bilirubin, and conjugated bilirubin were associated with the blood concentration of PCB adjusting for sex, age, drinking habit, smoking habit and body mass index (BMI). Because the distribution of the serum levels was strongly skewed to the right except that of serum concentration of total cholesterol, they were log transformed to approximate to the Normal distribution. The association between age and the blood concentration of PCB was significant (P0.001), although the associations of sex, drinking habit, smoking habit and BMI to the blood concentration of PCB were not significant. With the adjustment for sex, age, drinking habit, smoking habit and BMI, the serum concentrations of triglycerides and total cholesterol were significantly associated with the blood PCB level expressed by loge (blood concentration of PCB in ppb-1) (P = 0.02 and P0.001, respectively). The associations of serum levels of GOT, GPT, gamma-GTP, total bilirubin and conjugated bilirubin to the PCB level were not significant. The results of this study suggests the need of careful observation on the serum lipids of Yusho patients, especially those with high concentration of blood PCB, because the serum concentrations of total cholesterol and triglycerides are prominent risk factors of heart diseases.

We report a case of a non-Hodgkin's lymphoma (NHL) patient treated successfully with combination chemotherapy during pregnancy who delivered a full-term baby. A 29 year-old patient with cervical and inguinal lymphadenopathy in the 27th week of gestation was referred to our hospital. The diagnosis of lymph node biopsy was NHL (diffuse, large cell type with B-cell phenotype). Three courses of CHOP regimen (adriamycin, cyclophosphamide, vincristine and prednisolone) were given before delivery. The patient has been in complete remission for three years and her baby has been in normal development. Our case supports previous reports that chemotherapy in the third trimester may be given safely on NHL patients.

An in vivo gene transfer technique for living mouse testes was used to develop a novel transient expression assay system for transcriptional regulatory elements of spermatogenic specific genes. The combination of DNA injection into seminiferous tubules and subsequent in vivo electroporation resulted in an efficient and convenient assay system for gene expression during spermatogenesis. The transfer of the firefly luciferase reporting gene driven by the Protamine-1 (Prm-1) enhancer region revealed a significant increase in the activity of the reporter enzyme. Histochemical studies of the transfer of the lacZ gene driven by the Prm-1 enhancer showed specific lacZ expression only in haploid spermatid cells in adult testes, corresponding with the expression pattern of endogenous Prm-1. We were able to detect long-lasting transgene expression in the transfected spermatogenic cells. A group of spermatogenic differentiating cells maintained the transfected lacZ expression after more than 2 mo of transfection, suggesting that spermatogenic stem cells and/or spermatogonia could also incorporate foreign DNA and that the transgene could be transmitted to the progenitor cells derived from a transfected proliferating germ cell.

An 82-year-old man was admitted to our hospital in September 1996 due to dysphagia and cardiomegaly. Physical examination detected the fourth heart sound and a Levine III/VI systolic murmur in the cardiac apex. Surface lymph nodes were not palpable. LDH 662 IU/I was detected by laboratory examinations, and ultrasound cardiography showed grade 3 mitral regurgitation. Computed tomography revealed a huge mass in the posterior mediastinum, pressing the heart from the posterior direction. Thereafter, a left pleural effusion developed and aspiration was performed. Cytological examination of the fluid showed clusters of lymphoid cells with a positive immunophenotype for CD10, CD19 and HLA-DR. Chromosome analysis revealed complex abnormal karyotypes including t(8;14) (q24;32). A diagnosis of B cell lymphoma was made, and combination chemotherapy consisting of cyclophosphamide, THP-adriamycin, vincristine, and prednisolone was initiated. The patient's mass disappeared promptly, and his mitral reguration subsided. We reported this case because malignant lymphoma of the posterior mediastinum is rare, and because we are unaware of any previous reports of malignant lymphoma causing acute mitral regurgitation.

Aprindine was administered for 12 months to 8 hemodialysis patients suffering from arrhythmias. The serum aprindine concentration ranged from 0.3 to 0.6 microgram/ml, and did not increase with time during the 1-year treatment period. The PQ interval was temporarily prolonged in the first and second months, but the QRS and QT intervals were not changed by chronic aprindine treatment. The changes of the PQ interval in the second month of treatment were directly correlated with the serum aprindine concentration. No alterations of the ECG findings were observed when aprindine was discontinued. The cardiothoracic ratio (chest radiography) and laboratory findings were also not influenced by either aprindine treatment or its withdrawal. In conclusion, aprindine may be safely administered for at least 1 year to arrhythmia patients on maintenance hemodialysis.

We conducted a clinical trial to increase the chemosensitivity of residual leukemic cells by combining G-CSF to marrow-ablative chemotherapy, including cytosine arabinoside (Ara-C), and facilitated by autologous blood cell transplantation (ABCT) for treatment of acute myelogenous leukemia (AML) in first complete remission. A total of 16 patients were consecutively treated with granulocyte colony-stimulating factor (G-CSF)-combined high-dose chemotherapy (busulfan, etoposide and Ara-C) followed by autotransplantation of peripheral blood progenitor cells, which had been collected after the consolidation chemotherapy. At a median follow-up time of 44.5 months, the probability of 5-year event-free survival was 74.5% with only three leukemic relapses. This preliminary observation suggests the effectiveness of G-CSF-combined conditioning and ABCT as a post-remission therapy for AML.

To investigate the role of the 2'-hydroxy group at the C-13 side chain of docetaxel in the antitumor activity, we prepared several 2',2'-difluoro derivatives of docetaxel and evaluated their cytotoxicity against mouse leukemia and human tumor cell lines and their microtubule disassembly-inhibitory activity. These analogues were prepared by esterification of protected 10-deacetylbaccatin III (21) with appropriate alpha, alpha-difluorinated carboxylic acids (Charts 1 and 2). Among these 2',2'-difluorodocetaxel derivatives, 2',2'-difluorodocetaxel (23b) was approximately 3-10 times as active as 2'-fluorodocetaxel (29a) in terms of cytotoxicity. In addition, the 3'-(2-furyl) (23h) and 3'-(2-pyrrolyl) (23p) analogues showed activity comparable or superior to that of docetaxel (2).

Patients with poorly controlled noninsulin dependent diabetes mellitus (NIDDM) are shown to have higher bone mass. However, the influence of changes in glycemic control on bone turnover is not known. To clarify whether metabolic improvement of poorly controlled NIDDM affects bone turnover, markers for glucose, mineral, and bone metabolism were assessed before and after glycemic control for 3 weeks in 78 poorly controlled NIDDM patients with initial hemoglobin A1c over 8%. Metabolic improvement caused a reduction in urinary calcium (Ca) and phosphate (Pi) and serum 1,25(OH)2D levels, and an increase in serum Pi without changes in serum Ca or parathyroid hormone levels. Bone resorption markers, urinary deoxypyridinoline (Dpd) and type I collagen carboxy-terminal telopeptide (CTx), as well as a bone formation marker, serum bone type alkaline phosphatase (BALP), were reduced. However, another bone formation marker, serum osteocalcin (OC), was low before treatment and was elevated after treatment. The decrease in Dpd, CTx and BALP, but not the increase in OC, correlated with each other and with the improvement in glycemic indices. In conclusion, metabolic improvement of poorly controlled NIDDM decreases bone turnover within a short period. Thus, glycemic control may protect NIDDM patients from bone loss. It is possible that serum OC is affected by hyperglycemia per se, and may not correctly reflect bone turnover.

To investigate the frequency of symptoms and signs and their relationships with blood PCB (polychlorinated biphenyls) levels, twenty-five years after outbreak, we analyzed the data of 276 Yusho patients (male/female: 137/139) who had received health examination in 1993. For this purpose, 31 examination items which correspond or relate to the diagnostic criteria for Yusho (1976) were selected from the examination form. Mean blood PCB concentration in the subjects was 4.69 ppb with the highest value of 31.0 ppb (median : 4.0 ppb). The symptoms for which the proportion exceeded 60% were general fatigue, headache and numbness in extremities. Chronic bronchitis-like symptoms, such as cough and sputum, were observed in 50% of the subjects. Next, the subjects were classified into approximate quartiles of blood PCB:3.00, 3.00-4.06, 4.07-5.99, and 6.00+ppb. The distributions of subjects at four levels of blood PCBs were compared between the groups with or without each symptom or sign, using the Cochran-Mantel-Haenszel test. Significant differences were observed for comedones in the trunk (P = 0.02) and other regions (P = 0.02); acneiform eruptions in the genital regions (P = 0.01) and gluteal regions (P = 0.01); and hypersecretion in the Meibomian gland (P = 0.04). Thus, the typical skin and eye symptoms in Yusho patients still persist showing a close relation with blood PCB concentration.

Nicardipine is a potent arteriolar vasodilator with a negligible negative inotropic effect. Although intravenous administration of this drug has been reported to be effective in the treatment of heart failure, the optimal dose by this route is not clear. This study was designed to determine the optimum dose for the intravenous infusion of nicardipine in the treatment of heart failure. In Trial 1, nicardipine was administered intravenously at a dose of 0.5 microgram/kg per min to 14 patients with acute heart failure. The dose was increased to 1.0 microgram/kg per min in 13 cases with marked improvement at 2 h. In Trial 2, nicardipine was administered in a double-blind manner to 53 patients at 3 different rates of infusion for 2 h: 1.0 (Group 1, n = 19), 2.0 (Group 2, n = 15), and 3.0 (Group 3, n = 19) micrograms/kg per min. Neither heart rate nor mean right atrial pressure changed in any of the 3 groups. Favorable hemodynamic effects were evident in all groups beginning 30 min after the start of infusion, with an increase in cardiac index (control vs 2 h after infusion, L/min per m2) (Group 1: 2.2 +/- 0.4 vs 3.1 +/- 0.8, Group 2: 2.2 +/- 0.4 vs 2.9 +/- 0.5, Group 3: 2.3 +/- 0.3 vs 3.1 +/- 0.7, all p0.01 compared to the control) and a decrease in diastolic pulmonary artery pressure (Group 1: 26 +/- 10 vs 19 +/- 7, Group 2: 27 +/- 10 vs 20 +/- 8, Group 3: 26 +/- 7 vs 18 +/- 5 mmHg, all p0.01). The decrease in systolic pressure was greatest in Group 3 (Group 1: 141 +/- 31 vs 119 +/- 18, Group 2: 149 +/- 25 vs 118 +/- 17, Group 3; 147 +/- 27 vs 107 +/- 14 mmHg, all p0.01 compared to control, and p0.05 between Groups 1 and 3). The intravenous drip infusion of nicardipine is effective in the treatment of heart failure by inducing an increase in cardiac output and a decrease in pulmonary artery wedge pressure. The optimal dose in this study was 1.0 microgram/kg per min.

To identify the clinical significance of the isointegral body surface map of the QRST interval (QRST map) and the occurrence of repolarization abnormalities in patients with hypertrophic cardiomyopathy (HCM), the QRST map and signal-averaged electrocardiogram were evaluated in 50 patients with HCM, in 33 of whom the results were compared with nuclear images both for radioiodine-labeled fatty acid metabolism and for radiothallium perfusion. The QRST departure map was used to determine two parameters of difference between patient and control recordings: the subnormal area (the number of lead points at which the departure index values were negative and lay more than 2 SDs from the mean of the normal control group) and the subnormal minimum (the absolute value of the minimum in the departure map). Late potentials were detected in 6 (12%) of the 50 patients; they were observed in 3 of the 5 patients with dilated-phase HCM but in only 3 (7%) of the other 45 patients. The subnormal area and minimum values were lower in nonobstructive HCM than in dilated-phase HCM. Of the 33 patients examined by myocardial imaging, 28 (33%) had a filling defect or decreased uptake, as shown on fatty acid metabolic images, and 10 of the 28 also showed abnormal myocardial perfusion images, while the 18 others showed normal perfusion images. These 28 patients showed significantly larger values of the subnormal area and minimum than patients with normal results in both image tests, regardless of whether or not myocardial perfusion imaging abnormalities were present. The localization of filling defects or of decreased uptake presented in fatty acid metabolic images corresponded to the position of the minimum on the QRST departure map. These results suggest that the QRST map is useful for detection of repolarization abnormalities in HCM and that these abnormalities are highly related to impaired fatty acid utilization of the myocardium.

The effects of microwave plasma treatments on the physical and electrical characteristics of silicon dioxide films are discussed. Plasma treatments significantly improve the characteristics at low temperatures. Differences in the type of inert gas, O2 partial pressure, and total pressure cause differences in the plasma energy and active species concentrations, which affect reduction in the impurity concentrations, generation of dangling bonds, and effective working depth of the plasma. The changes in the electrical characteristics of the plasma-treated oxide films are consistent with those in the physical characteristics. The plasma conditions that result in the best improvements are determined.

Trypanosoma cruzi, the causative agent of Chagas' disease, exhibits two different developmental stages in mammals, the amastigote, an intracellular form that proliferates in the cytoplasm of host cells, and the trypomastigote, an extracellular form that circulates in the bloodstream. We have already established an in vitro culture system using mammalian host cells (HeLa) infected with T. cruzi in which the time course of parasite growth is determined quantitatively. We adopted this system for the screening of anti-T. cruzi agents that would ideally prove to be effective against trypanosomes with no toxicity to the host cell. Of the purine analogs tested, allopurinol markedly inhibited the growth of amastigotes in a dose-dependent manner, with no lethal effect on trypomastigotes. 3'-Deoxyinosine and 3'-deoxyadenosine also suppressed T. cruzi growth inside the host cell, with the concentrations causing 50% growth inhibition being 10 and 5 microM, respectively, in contrast to a concentration causing 50% growth inhibition of 3 microM for allopurinol. Among the pyrimidine analogs examined, 3'-azido-3'-deoxythymidine (zidovudine) significantly reduced the growth of the parasite at concentrations as low as 1 microM. The anti-human immunodeficiency virus agents 2',3'-dideoxyinosine and 2',3'-dideoxyadenosine caused a decrease in amastigote growth, while 2',3'-dideoxycytidine and 2',3'-dideoxyuridine had no inhibitory effect. When Swiss 3T3 fibroblasts were used as host cells, allopurinol, 3'-deoxyinosine, 3'-deoxyadenosine, and 3'-azid-3'-deoxythymidine also markedly inhibited T. cruzi proliferation. These results indicate that our culture system is useful as a primary screening method for candidate compounds against T. cruzi on the basis of two criteria, namely, intracellular replication by the parasite and host-cell infection rate.

The prevention of influenza continues to be a major public health concern, and a program of vaccination has been promoted, especially to high-risk individuals such as the elderly. In addition, concerted efforts are being expended in many developed countries in order to better cope with the next influenza pandemic. These efforts include enhancing influenza virus surveillance, improving vaccine production and its delivery systems, centralizing vaccine distribution and establishing priorities, etc. In Japan, on the other hand, influenza is only considered a minor illness, and thus little attention has been give to measures against influenza. To disseminate information on recent international trends in influenza control to Japanese public health specialists, I herein outline the recommendations made at two recent international meetings: "Pandemic Influenza: Confronting a Reemergent Threat" held in the u.s., at Bethesda, Maryland, in December 1995; and "The 7th European Meeting of Influenza and Its Prevention" held in Berlin. Germany, in September 1993. Since a routine system capable of responding adequately to annual epidemics is considered to be the best defense against a pandemic, I also describe the present state of influenza control in other countries to contrast it with that in Japan: the target groups for special vaccination programs recommended by the U.S. Advisory Committee on Immunization Practices; the recommendations for influenza vaccination and reimbursement for the vaccination of recommended groups in developed countries: and influenza vaccine distribution in Japan and the U.S., 1980-1994. At present in Japan, the efficacy of the currently used inactivated vaccine is regarded as either very low or none at all. There is also no official national recommendations as to what groups should be targeted for active immunization, nor any system for vaccination reimbursement. Public health specialists in Japan, therefore need to fully understand Japan's peculiar situation and, as a result, better recognize the importance of influenza and its prevention.

Using a prospective, randomized design, we tested our hypothesis that the augmentation of diastolic pressure by intraaortic balloon counterpulsation (IABP) would improve the late patency of the occluded coronary artery in patients with early failure of thrombolytic therapy.Rescue angioplasty is often performed in patients in whom thrombolysis has failed, although 30% to 60% of the infarct-related arteries that are closed early after thrombolytic therapy will open later with conservative therapy.The study included 45 patients in whom thrombolysis had failed, despite treatment with intravenous tissue-type plasminogen activator (alteplase 0.75 mg/kg body weight) delivered over 60 min within 12 h of the onset of symptoms. All patients underwent coronary angiography 60 min after initiation of thrombolytic therapy (baseline), and Thrombolysis in Myocardial Infarction (TIMI) grade 0, 1 or 2 flow was defined as failed thrombolysis. The patients were randomized to groups receiving IABP for 48 h (n = 23) or conservative therapy (n = 22, control subjects) at the end of cardiac catheterization. The late patency of the infarct-related artery, the primary end point of the study, was evaluated 3 weeks after myocardial infarction. Stenosis of the infarct-related artery was measured using a computer-assisted quantitative angiographic system in blinded manner. Data are expressed as mean value +/- SEM.There was no difference with regard to the baseline value for TIMI flow grade between the groups. However, 3 weeks after myocardial infarction, the patients treated with IABP had a significantly higher frequency of TIMI flow grade 3, lower residual percent stenosis and larger minimal lumen diameter of the infarct-related artery than did the control subjects (74% vs. 32%, p0.05; 42 +/- 5% vs. 68 +/- 6%, p0.01; and 1.6 +/- 0.1 vs. 0.9 +/- 0.2 mm, p0.01, respectively).These findings suggest that in patients with early failure of thrombolytic therapy, IABP may improve late patency of the occluded coronary artery, probably due to augmented perfusion pressure.

Human umbilical cord blood has been used as an alternative source of cells for repopulating bone marrow in allogenic bone marrow transplantation in children. The number of transplantations of umbilical cord blood cells is increasing worldwide. Umbilical cord blood was collected from 52 subjects at a single collection at the time of delivery, and separated using the red blood cell sedimentation technique. Nucleated cells harvested from the fraction enriched with white blood cells were used for an assay to detect colony-forming unit granulocyte-macrophage (CFU-GM) derived cell colonies and a flow cytometric analysis of CD34+ cells under variable conditions. The number of hematopoietic progenitor cells that might be reconstituted to bone marrow was estimated. The mean duration time from the beginning of delivery to complete collection of cord blood was 9.9 min (range 5 to approximately 20 min). The mean volume of umbilical cord blood for the 52 collections was 69.1 ml (range 15-135 ml), containing 1.001% CD34+ cells (range 0.21% approximately 2.63%) and 4 x 10(5) cells of CFU-GM derived colonies (range 0.2 x 10(5) approximately 10.0 x 10(5) cells) within 24 h at 4 degrees C after delivery of the infant. There was no contamination by the mother's lymphocytes according to cytogenetic analysis using pYNH24, which is a probe with a variable number of tandem repeat markers. These findings indicated that umbilical cord blood can be easily collected using the syringe method and separated by the red blood cell sedimentation technique using 6% hydroxyethylstarch. Within 24 h at 4 degrees C, hematopoietic progenitor cells were well detected using an assay for CFU-GM derived colonies and were measured by flow cytometric analysis. However, the instability of the number of hematopoietic progenitor cells must be resolved for safe transplantation of hematopoietic progenitor cells as a source of cells for repopulating bone marrow in children.

Anesthetic considerations of 21-mo-old and 4-yr-old sisters with Beckwith-Wiedemann syndrome during surgical repair of cleft palate and reduction of macroglossia are presented and discussed. This syndrome is characterized by exomphalos, macroglossia, gigantism, hypoglycemia in infancy, and many other clinical features. This syndrome is also known as exomphalos, macroglossia, and gigantism (EMG) syndrome. Principal problems associated with anesthetic management in this syndrome are hypoglycemia and macroglossia. Careful intraoperative plasma glucose monitoring is particularly important to prevent the neurologic sequelae of unrecognized hypoglycemia. It is expected that airway management would be complicated by the macroglossia, which might cause difficult bag/mask ventilation and endotracheal intubation following the induction of anesthesia and muscle paralysis, so preparations for airway difficulty (e.g., awake vocal cord inspection) should be considered before induction. A nasopharyngeal airway is useful in relieving postoperative airway obstruction.

In this study, our induction methods of endotracheal anesthesia was evaluated with reference to electrocardiogram, hemodynamic status and arterial blood gas analysis on 153 patients. From the beginning of induction, electrocardiogram was recorded continuously to the completion of intubation. The blood pressure and heart rate were also measured. Arterial blood samples were taken at 40 seconds of apneic period after the mask was removed from the patient's face (CONT group), at 40 seconds of apnea with intratracheal spray (LIDO group), and after intubation following intratracheal spray (INT group). In the electrocardiographic survey, arrhythmias during intubation were rare (1/113, 0.9%). PaCO2 values in INT group showed a significant elevation (+ 14.0 mmHg; p0.01) compared to these in CONT group. As a result of careful and gentle induction techniques, the incidence of arrhythmias during intubation was very low. However, an elevation of PaCO2 was not avoidable, even in smooth and successful intubation. In conclusion, the importance of more adequate ventilation coupled with skillful intubation in a shorter period to avoid hypercapnia and arrhythmias is appreciated again in the endotracheal anesthesia for the maxillofacial surgical patients with anatomical airway problems.

Immunostimulative effects of chicken egg white derivatives (EWD) on phagocytic responses of peripheral blood mononuclear cells (MNC) and polymorphonuclear cells (PMN) in dogs were evaluated by flow cytometric analysis. Peripheral blood leukocytes (PBL) cultured with EWD showed the enhanced phagocytic response. The response was maximal when PBL were cultured with 100 - 400 micrograms/ml of EWD for 3 - 12 hr. Furthermore, significantly increased phagocytic responses were also induced even when PBL were cultured with protein components (200 micrograms/ml) of EWD such as conalbumin, flavoprotein and ficin-papain inhibitor for 3 hr. In addition, the enhancing effect of EWD on the phagocytic responses was also observed in MNC cultured with EWD (200 micrograms/ml) for 4 hr but not in PMN cultured with EWD in the same procedures. The supplement of the supernatant (20%) of MNC cultured with EWD (200 micrograms/ml) for 24 hr at 37 degrees C to PBL and MNC resulted in the enhancement of their phagocytic responses. In contrast, the supernatant of PMN cultured with EWD for 24 hr at 37 degrees C did not show any significant enhancing effect on the phagocytic responses of PBL, MNC and PMN. These results suggest that EWD has an enhancing effect on phagocytosis of MNC and PMN, which may be mediated through active humoral substances produced by EWD-stimulated MNC.

A 10-year retrospective review of epithelial carcinoma of the ovary was performed about 95 patients which were diagnosed and treated at the Oita Medical University Hospital. The patients' ages at the first diagnosis ranged from 15 to 85 years with a mean of 51.6 years. Twenty-two of 95 patients (23.2%) were below the age of 40. Most patients analysed in this study complained of lower abdominal pain, lower abdominal mass, and/or lower abdominal fullness. Sixteen of 22 patients under the age of 40 (72.7%) and 27 of 73 patients over the age of 40 (37.0%) were diagnosed as having mucinous cystadenocarcinoma. The incidence of mucinous cystadenocarcinoma below the age of 40 was significantly higher than that over the age of 40 (p0.005, chi 2-test). Eleven patients below the age of 40 had FIGO stage Ia grade 1 disease and 2 of these patients were pregnant. The incidence of stage Ia disease under the age of 40 was significantly higher than that over the age of 40 (p0.005, chi 2-test). Both pregnant patients and 5 other patients with stage Ia disease were treated with only unilateral salpingo-oophorectomy. All patient with stage Ia disease had no evidence of recurrence within 5 years. This suggests that conservative surgery may be considered as the treatment for the FIGO stage Ia grade 1 ovarian cancer.

To investigate whether intraoperative rupture of epithelial ovarian cancer. influences the prognosis.Between 1984 and 1994, 46 patients with stage Ia and Ic epithelial ovarian cancer were treated at Oita Medical University Hospital. Of 46 patients, 20 had stage Ia tumors, 16 stage Ic secondary to capsular invasion-serosal disease or positive ascites or washings (stage Ic-ascites), and 10 stage Ic secondary to intraoperative rupture (Ic-rupture). Survival analysis was performed to compare the three groups of patients.The ages (mean +/- SD) of patients with stage Ia, Ic-ascites and Ic-rupture at the first diagnosis were 40.1 +/- 17.0, 47.6 +/- 13.4 and 52.8 +/- 15.7, respectively. The age of the stage Ia group tended to be lower than those of the Ic-ascites and Ic-rupture groups. At operation, ovarian tumors of all patients in the Ic-rupture group were firmly adhered to surrounding organs, had markedly thin weak cyst walls and were easily ruptured during operation. Fourteen of 20 patients in the Ia group (70%), 5 of 16 patients in the Ic-ascites group (31.3%) and 3 of 10 patients in the Ic-rupture group (30%) showed signs of mucinous cystadenocarcinoma. The incidence of mucinous cystadenocarcinoma in Ia group was significantly lower than in the Ic-ascites (p0.025, chi 2-test) and Ic-rupture (p0.05, chi 2-test) groups. The Kaplan-Meier survival plot for stage Ia, Ic-ascites and Ic-rupture patients revealed a probability of 5-year survival of 100%, 87.5% and 63.5%, respectively. The probability of 5-year survival in the Ic-rupture group tended to be lower than that in other groups.The results of our study suggest that intraoperative rupture of a malignant ovarian cystic tumor may worsen the prognosis of patients with the FIGO stage I epithelial ovarian cancer.

The correlation between blood PCB concentration and clinical manifestation of symptoms was investigated in 259 chronic "Yusho" patients, using the information obtained from the nationwide health examination conducted in 1988, twenty years after the outbreak. Concentrations of blood PCBs ranged 0.6-32.0 ppb (mean; 4.78), and they were categorized into approximate quartile for analysis. For general fatigue, odds ratios at 2.7+, 4.1+, and 6.1+ ppb were 2.4, 3.6, and 3.1, respectively, with a reference category of2.7 ppb (test for trend; p0.005). For numbness in extremities, the corresponding odds ratios were 2.8, 2.8, and 2.9(p0.005). For comedone, they were 1.4, 1.0, and 4.0 on face (p0.025); and 3.6, 4.6, and 9.5 on trunk (p0.005), respectively. A distinctive increase in odds ratio was observed at 2.7 ppb for these two subjective symptoms; and at 6.1 ppb for skin symptoms. The blood PCB concentrations among patients were relatively close to the normal subjects. Therefore, the observed correlations may be due to the effects of PCBs with a peculiar pattern in components, PCQs or PCDFs, taken and retained in the patients. Association with blood PCBs was also suggested for headaches; abnormal breath sounds; and acneiform eruptions in the genital region, but were statistically insignificant. None of the eye symptoms showed significant association with blood PCBs.

A series of 584 patients with cervical invasive cancer were included in the retrospective study on the efficacy of long-term oral maintenance chemotherapy with antimetabolites (Fluorouracil or Tegaful). The patients were histologically classified into the squamous cell carcinoma (SCC) group and the adenocarcinoma (AD) group. In the SCC group (n = 518), 163 patients were given more than 300 mg/day of antimetabolite tablets for one year or more after the main therapy (hysterectomy or pelvic irradiation). In the AD group (n = 66), 36 patients were treated with the same dose of antimetabolites. The Kaplan-Meier overall and cancer specific survival analysis estimates that the chronic administration of antimetabolites did not improve the cumulative 5-year survival in the SCC group. In contrast, the cumulative 5-year survival rate in the AD group treated with antimetabolites (88%) was significantly higher than that without chemotherapy (64%) by Kaplan-Meier analysis. This significant improvement in the survival rate in the AD group due to antimetabolites was notable in patients in FIGO stage I or II treated with radical or semiradical hysterectomy, these results indicate that oral adjuvant chemotherapy with antimetabolites is useful for cervical adenocarcinoma, but not for squamous cell carcinoma.

An increasing number of dental patients are taking beta-adrenergic blockers for the treatment of hypertension or angina pectoris. If epinephrine-containing local anesthetics are administered to such patients, interactions between epinephrine and the beta-blocking agent may induce cardiovascular complications. We assessed in volunteers the effects of intraoral injection with 2% lidocaine containing 1:80,000 epinephrine (L-E) on cardiac function after pretreatment with the beta-blocking agent pindolol. M-Mode echocardiography was used for the assessment. The injection of L-E after administration of pindolol did not alter cardiac preload, whereas it reduced the stroke volume, due to an increase in afterload and a decrease in myocardial contractility. Reductions in stroke volume and heart rate led to a decrease in cardiac output. Because total peripheral vascular resistance increased markedly, blood pressure was elevated despite the reduced cardiac output. These results suggest that cardiac function of dental patients on beta-blocker therapy can be adversely affected by epinephrine-containing local anesthetics. Therefore, when such an anesthetic solution has to be used in patients on beta-blocker therapy, careful systemic monitoring is needed.

The effect of an upstream DNA curvature on the strength of the herpes simplex virus thymidine kinase (TK) promoter was investigated by employing luciferase assay. A set of double-stranded oligonucleotides, each with an unique DNA configuration, were synthesized and substituted into an upstream region of the promoter. It was revealed from the assay that both plane and space curves exerted a negative influence upon the strength of the promoter.

In order to examine the reliability of conventional views in predicting the degree of radio-opacity, irrespective of soft tissue or fluid seen in chronic sinusitis in adults, a comparison has been made between the results of evaluations by two routine views (Caldwell's and Waters') and by CT in axial scans. Ninety-seven sides (61 case) were included in the study. The radio-opacity was classified into three groups according to the degree of aeration or radiolucency. The diagnosis of plain films were classified into three categories (matched diagnosis, over-diagnosis, and under-diagnosis) in comparison to the radio-opacity depicted by corresponding CT scans. The incidences of matched diagnosis are, in the order of percentages: maxillary sinus (78.4%), frontal sinus (71.1%), nasofrontal area (66.0%), anterior ethmoidal cells (52.6%), and posterior ethmoidal cells (52.6%). The incidence of over-diagnosis is highest in the posterior ethmoidal cells (52.6%) and lowest in the maxillary sinus (20.6%). The incidence of under-diagnosis is highest in the anterior ethmoidal cells (24.7%) and lowest in the maxillary sinus (1.0%).

In order to evaluate the benefit derived by conventional views in the initial diagnosis of fractures of the orbital walls, a clinical study was designed to compare the results of evaluations by plain films and coronal CT scans. The conventional Caldwell's and Waters' views will provide a fairly reliable result as to the presence of orbital fractures: orbital floor (anterior in 78%, posterior in 73%), medial orbital wall (anterior in 71%, posterior in 72%), and ethmoid-maxillary plate in 64%. False-negative diagnosis was seen at the anterior portion of the floor in 13%, at the anterior portion of the medial orbital wall in 7%, and at the ethmoid-maxillary plate in 11%. False-negative diagnosis was seen at the orbital floor (anterior in 9%, posterior in 10%), at the medial orbital wall (anterior in 21%, posterior in 29%), and at the ethmoid-maxillary plate in 21%. Our results agree well with those of the past reports.

Introduction Influenza is a potentially serious infection among haemodialysis (HD) patients, and the antibody response to vaccines among HD patients is thought to be weaker than that in healthy people. We conducted this study for the purpose of evaluating the immunogenicity and reactogenicity of the pandemic vaccine among patients on long-term HD. Materials and Methods During the 2009–2010 influenza season, 170 HD patients (108 men, 62 women; mean age: 62.2±13.2 years, mean and max duration of HD: 12.3 and 35 years, respectively) received two doses of monovalent inactivated unadjuvanted vaccine. Immunogenicity of the vaccine was evaluated according to conventionally used international criteria (EMEA, 1997; FDA, 2007). Results The geometric mean of HI titre 4 weeks after vaccination increased from a pre-vac level of 7.0 to 32.5 for the first injection, and to 37.8 for the second injection. The sero-conversion rate was 48% and sero-protection rate was 54% for the first injection, and 53% and 57% respectively for the second injection. The occurrence of systemic rush was significantly higher compared with healthy adults. Conclusions A two-shot influenza vaccination series showed a booster effect and achieved the EMEA criteria at the first vaccination. No serious adverse events were detected, but systemic rush occurred frequently. A Dysfunction in detoxification ability due to the patients9 renal disease may have caused this.

Associations of blood PCB concentration with serum levels of triglyceride, gamma-GTP, total-, and conjugated-bilirubin were investigated in "Yusho" patients twenty years after outbreak, using the information obtained from the medical examinations in 1988 and 1989. Study subjects were 259 patients in 1988, and 268 patients in 1989, including 190 patients who consecutively received both examinations. Blood PCB concentrations (mean +/- SE) were 4.78 +/- 0.22 ppb in 1988, and 4.47 +/- 0.17 ppb in 1989. The results of blood-chemical analysis were compared among four categorized concentrations of blood PCB, using the analysis of variance. Significant difference was observed for triglyceride (1988: p0.025, 1989: p0.005), but not for gamma-GTP, total-, and conjugated-bilirubin. In 1988, the mean triglyceride levels were 108, 137, 145, and 166 mg/dl at2.7,or = 2.7,or = 4.1, andor = 6.1 ppb of blood of PCB, respectively. Corresponding figures in 1989 were 106, 129, 154, and 156 mg/dl at2.7,or = 2.7,or = 4.0, andor = 5.7 ppb of blood PCB, respectively. Thus, clear positive association between blood PCB and serum triglyceride was observed in the patients twenty years after exposure.

Each of 36 patients who underwent tracheotomy for removal of malignant or benign tumors or for treatment of pneumothorax was infused with 2 g of aspoxicillin (ASPC, Doyle injection) intravenously over 1-hour period. ASPC concentrations determined at 1 postoperative time-point in tissues of the lung and trachea and in serum of each patient were analyzed pharmacokinetically to elucidate the transfer of ASPC to the thoracic tissues. The preventive effect of ASPC against postoperative infections was also investigated in 39 tracheotomy patients. 1. The analysis of ASPC concentrations in 36 patients with tracheotomy gave the following results; 1) The peak blood level (about 80 micrograms/ml) was attained at the end of infusion. The serum level then decreased with time to below about 10 micrograms/ml at 6 hours after the start of infusion, with an elimination half-life of about 1.4 hours, which was comparable to that in healthy adults. 2) Peak levels in the lung and tracheal tissues were achieved at about 30 minutes after the start of infusion, at levels of about 30 and 40 micrograms/g, respectively, which decreased to about 5 micrograms/g in both tissues at 6 hours after the start of infusion. 2. Thirty nine patients who were treated with ASPC before operation were examined for the preventive effect of ASPC against postoperative infections for 1 week after operation. No postoperative infection was noted in any patients and ASPC was found to be useful for prevention of postoperative infections. 3. No side effects or abnormal laboratory findings were noted in any patients. Based on the results of the transfer into the tissues of respiratory organs and preventive effect against postoperative infections, we have concluded that ASPC is useful for prevention of infections after thoracic operation.

To assess the effect of prenatal vitamin K1 on the coagulation status of newborns.We measured noncarboxylated prothrombin and performed the Normotest in two groups of 5-day-old infants whose mothers were given oral vitamin K1, 10 mg/day for 2 weeks at least 10 days before delivery, or were untreated.Noncarboxylated prothrombin was found in one of 74 treated women and 13 of 186 controls, a nonsignificant difference. The mean (+/- standard deviation) Normotest value was 59.6 +/- 10.1% (range 38.9-84.4) for the treated group and 53.4 +/- 9.9% (range 16.3-89.9) for the controls, a statistically significant difference (P.001).Based on the Normotest results, we suggest that vitamin K crosses the placenta and persists to activate the vitamin K-dependent coagulant factors until at least the fifth day of life. Thus, prenatal vitamin K1 administration may replace prophylaxis at birth.

In this paper the mechanism of excimer laser ablation of Si3N4 ceramics is analyzed. An image intensifier with minimum gate time of 3 ns was used for observing time resolved behavior of the plasma plume and the particles produced during ablation process in various ambient gas species and pressures. Absorption and scattering at wavelength of 248 nm and 532 nm were also measured in the plasma plume, respectively.High temperature plasma was produced at delay time around 4~20 ns, and propagate spherically at speeds around 5~15 km/s. The absorption coefficient of the plasma plume at 248 nm was about 3~10 mm−1, which corresponds to the electron densities of the order of 1019 cm−3. It was shown that the removal rate per unit incident laser fluence saturates at higher fluences because the laser-induced plasma absorbs the incident laser beam due to inverse Bremsstrahlung. Raleigh scattering of 532 nm from the decomposed particles of 5~20 nm in diameter initiated at delay time around 1 μs. At delay time later than 10 μs, the particle flow backwards towards the specimen surface was observed, which was considered to be caused by a cooling wave to produce the debris, and then were followed by bouncing at the surface and staying above the surface for several hundreds micro seconds. Deposition rate of the debris was as large as 20 nm/pulse in O2 atmosphere. The debris formation is shown to be closely related with the blast wave theory. The amount of the debris was reduced in lighter gases like He or reduced atmospheric pressure.In this paper the mechanism of excimer laser ablation of Si3N4 ceramics is analyzed. An image intensifier with minimum gate time of 3 ns was used for observing time resolved behavior of the plasma plume and the particles produced during ablation process in various ambient gas species and pressures. Absorption and scattering at wavelength of 248 nm and 532 nm were also measured in the plasma plume, respectively.High temperature plasma was produced at delay time around 4~20 ns, and propagate spherically at speeds around 5~15 km/s. The absorption coefficient of the plasma plume at 248 nm was about 3~10 mm−1, which corresponds to the electron densities of the order of 1019 cm−3. It was shown that the removal rate per unit incident laser fluence saturates at higher fluences because the laser-induced plasma absorbs the incident laser beam due to inverse Bremsstrahlung. Raleigh scattering of 532 nm from the decomposed particles of 5~20 nm in diameter initiated at delay time around 1 μs. At delay time later than ...

The region preceding the beta-lactamase promoter of Escherichia coli plasmid pUC19 has a DNA curvature (curved DNA or bent DNA). Studies using mutant plasmids showed that the curved DNA structure is required for efficient transcription of the beta-lactamase gene and suggested that the requisite shape is a small part of a right-handed coil. Based on these results, the possible functional significance of DNA curvature in transcription will be discussed.

A patient developed strongly negative T waves following anesthesia for maxillofacial surgery. The electrocardiogram was normal preoperatively, except for a single premature ventricular depolarization, and no abnormalities were noted during the operation. Postoperatively, the T wave gradually inverted in almost all leads and approached the criterion of -10 mm for giant negative T waves in V3 2 days postoperatively. The T wave returned to normal approximately 4 months later. Although the T-wave inversion in this patient may have been caused by surgical trauma to the sympathetic nerve supply to the heart or by myocardial infarction, the exact cause remains undetermined.

Sandwich ELISA were developed to quantitatively determine conglutinin (CG), mannan-binding protein (MBP), and serum amyloid-P component (SAP) in the sera of cattle. The ELISA system was found to have high repeatability for quantitation of these serum proteins at concentration as low as 5 ng/ml. From results obtained for 10 healthy cows aged 2 to 7 years, mean +/- SD serum concentrations were 56.5 +/- 14.4 micrograms of CG/ml, 2.37 +/- 0.87 micrograms of MBP/ml, and 11.14 +/- 3.92 micrograms of SAP/ml, respectively. Values in 6 healthy heifer calves aged 6 months were 3.45 +/- 1.22 micrograms/ml for CG, 1.71 +/- 0.96 micrograms/ml for MBP, and 5.45 +/- 2.75 micrograms/ml for SAP, respectively. Concentrations in 9 healthy bullocks aged 6 months were 1.83 +/- 0.66 micrograms/ml for CG, 1.04 +/- 0.63 micrograms/ml for MBP, and 4.9 +/- 1.13 micrograms/ml for SAP, respectively.

A 40-year-old female who had lung and liver metastases from malignant pheochromocytoma was treated with 3.7 GBq 131I-MIBG (metaiodobenzylguanidine). After the treatment, 131I-MIBG showed increased uptake in the metastatic lesions of the lung and liver. The size of tumor was no significant change on CT and MRI, but the intensity of liver metastases decreased gradually on MRI. Prior to the treatment, the levels of adrenaline and noradrenaline were high. One to three days after treatment, the level of these laboratory data further increased, but they gradually decreased in 1 to 3 months. These changes may be due to necrosis of tumor tissue.