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Patients with idiopathic Parkinson’s disease (PD) appear to have reduced capacity for detoxification of certain environmental compounds. The glutathione S-transferases (GSTs) are candidate genes for PD because they are involved in the metabolism of pesticides and cigarette smoke. We investigated the relationship of the seven GST polymorphisms ( GSTM1 deletion, GSTT1 deletion, GSTP1 rs1695, GSTO1 rs4925, GSTO1 rs11191972, GSTO2 rs156697 and GSTO2 rs2297235) and PD risk with special reference to the interaction with pesticide use or cigarette smoking among 238 patients with PD cases and 370 controls in a Japanese population. None of the GST polymorphisms were associated with PD. GSTO1 rs4925 and GSTO2 rs2297235 were found to be in strong linkage disequilibrium ( D ′ = 0.98). Cigarette smoking was significantly associated with decreased risk of PD. However, no interaction of smoking with any of the GST polymorphisms was observed. Self-reported pesticide use was not associated with increased risk of PD. There was no evidence of interaction between self-reported pesticide use and either GST polymorphism. Our results suggest that the tested GST polymorphisms did not play an important role in PD susceptibility in our Japanese population. Our study does not give evidence of interaction between the GST polymorphisms and smoking may although this study provided sufficient statistical power to detect modest interaction. As for interaction between GSTP polymorphisms and pesticide use, the power of this study to detect an interactive effect was low due to a small number of pesticide users. Future studies involving larger control and case populations and better pesticide exposure histories will undoubtedly lead to a more thorough understanding of the role of the GST polymorphisms in PD development.

The systemic use of steroids and habitual alcohol intake are two major causative factors in the development of idiopathic osteonecrosis of the femoral head (ONFH). To examine any interaction between oral corticosteroid use and alcohol intake on the risk of ONFH, we conducted a hospital-based case-control study of 71 cases with ONFH (mean age 45 years (20 to 79)) and 227 matched controls (mean age 47 years (18 to 79)). Alcohol intake was positively associated with ONFH among all subjects: the adjusted odds ratio (OR) of subjects with ≥ 3032 drink-years was 3.93 (95% confidence interval (CI) 1.18 to 13.1) compared with never-drinkers. When stratified by steroid use, the OR of such drinkers was 11.1 (95% CI 1.30 to 95.5) among those who had never used steroids, but 1.10 (95% CI 0.21 to 4.79) among those who had. When we assessed any interaction based on a two-by-two table of alcohol and steroid use, the OR of those non-drinkers who did use steroids was markedly elevated (OR 31.5) compared with users of neither. However, no further increase in OR was noted for the effect of using both (OR 31.6). We detected neither a multiplicative nor an additive interaction (p for multiplicative interaction 0.19; synergy index 0.95), suggesting that the added effect of alcohol may be trivial compared with the overwhelming effect of steroids in the development of ONFH.Cite this article: Bone Joint J 2013;95-B:320–5.

Nearly all epidemiologic studies examining the association between the risk of Parkinson's disease (PD) and diet have focused on single foods and specific nutrients. However, epidemiologic evidence for the association of dietary pattern with PD, namely the measurement of overall diet by considering the cumulative effects of nutrients is extremely limited. We conducted a hospital-based case-control study in Japan to examine the relationship between dietary patterns and the risk of PD.Patients with PD diagnosed using the UK PD Society Brain Bank criteria (n = 249) and controls without neurodegenerative diseases (n = 368) were recruited. At the time of recruitment, dietary intake during the preceding 1 month was assessed using a validated, self-administered diet history questionnaire. Dietary patterns from 33 predefined food groups (energy-adjusted food g/day) were extracted by factor analysis.Three dietary patterns were identified: 'Healthy', 'Western' and 'Light meal' patterns. After adjustment for potential non-dietary confounding factors, the Healthy pattern, characterized by a high intake of vegetables, seaweed, pulses, mushrooms, fruits and fish, was inversely associated with the risk of PD with a border-line significance (P for trend = 0.06). Multivariate Odds ratio (95% confidence intervals) for PD in the highest quartile of the Healthy pattern was 0.54 (0.32-0.92) compared with the lowest quartile. No associations with PD were detected for the other two dietary patterns.In this case-control study in Japan, a dietary pattern consisting of high intakes of vegetables, fruits and fish may be associated with a decreased risk of PD.

Three previous cohort studies in the USA reported that dairy product consumption was significantly associated with an increased risk of Parkinson's disease (PD) in men, but not in women. We examined the relationship between consumption of dairy products, calcium, and vitamin D and the risk of PD using data from a multicenter hospital-based case-control study in Japan. Included were 249 cases within 6 years of onset of PD based on the UK PD Society Brain Bank clinical diagnostic criteria. Controls were 368 inpatients and outpatients without a neurodegenerative disease. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, pack-years of smoking, years of education, body mass index, and dietary factors including cholesterol, dietary glycemic index, vitamin E, β-carotene, vitamin B(6), caffeine, iron, and alcohol. Total dairy product consumption was not materially associated with the risk of PD (P for trend = 0.62). No evident relationships were observed between intake of milk, yogurt, cheese, or ice cream and the risk of PD (P for trend = 0.75, 0.63, 0.59, and 0.35, respectively). There were no measurable associations between consumption of calcium or vitamin D and PD (P for trend = 0.37 and 0.69, respectively). No significant interactions were observed between the dietary exposures and sex regarding PD. Our results suggest that intake of dairy products, calcium, and vitamin D was not related to PD, regardless of sex. However, such null relationships might be a consequence of PD.

antioxidant vitamins are expected to protect cells from oxidative damage by neutralizing the effects of reactive oxygen species. However, epidemiological evidence regarding the associations between antioxidant vitamin intake and Parkinson's disease (PD) is limited and inconsistent. We investigated the relationship between dietary intake of selected antioxidant vitamins, vegetables and fruit and the risk of PD in Japan using data from a multicenter hospital-based case-control study.included were 249 patients within 6 years of onset of PD. Controls were 368 inpatients and outpatients without a neurodegenerative disease. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, pack-years of smoking, years of education, body mass index, dietary intake of cholesterol, alcohol, total dairy products, and coffee and the dietary glycemic index.higher consumption of vitamin E and β-carotene was significantly associated with a reduced risk of PD after adjustment for confounders under study: the adjusted odds ratio in the highest quartile was 0.45 (95% confidence interval [CI]: 0.25-0.79, P for trend = 0.009) for vitamin E and 0.56 (95% CI: 0.33-0.97, P for trend = 0.03) for β-carotene. Stratified by sex, such inverse associations were significant only in women. No material relationships were shown between intake of vitamin C, α-carotene, cryptoxanthin, green and yellow vegetables, other vegetables, or fruit and the risk of PD.higher intake of vitamin E and β-carotene may be associated with a decreased risk of PD.

To assess the association between active and passive smoking and the risk of Parkinson's disease (PD), a case-control study with 249 PD patients and 369 controls was carried out in Japan.Information on smoking was obtained through a self-administered questionnaire. Adjustment was made for age, sex, region of residence, educational level, and occupational exposure.Ever having smoked cigarettes was associated with a reduced risk of PD [adjusted odds ratio = 0.38; 95% confidence interval (CI): 0.24-0.59]. Risk for former smokers was intermediate between the high risk for never smokers and the low risk for current smokers. Adjusted odds ratios for former and current smokers were 0.51 (95% CI: 0.32-0.82) and 0.12 (95% CI: 0.05-0.26), respectively. There was an inverse dose-response gradient with pack-years smoked. No significant association was detected for passive smoking exposure.Our results appear to confirm data from previous epidemiological studies.

This study was performed to evaluate the significance of pS2 and MUC1 expressions in ulcerative colitis (UC)-associated colorectal neoplasias. Tissues were collected from 6 patients with UC-associated colorectal neoplasias treated surgically. Specimens were 13 adenocarcinomas, 40 dysplasias (20 high-grade dysplasias, 20 low-grade dysplasias), and 60 normal mucosae. Tissues were also collected from patients without UC treated surgically or endoscopically. pS2, p53, and MUC1 expressions were examined immunohistochemically and compared. The K-ras codon 12 mutation was investigated by single-strand conformation polymorphism analysis. In patients with UC, the incidence of pS2 expression was significantly higher (p

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.

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.

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.

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.

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.

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.

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 observe the clinical course after reperfusion and recovery from myocardial stunning of the left ventricular anterior wall, we prospectively reviewed and analyzed cardiac enzymes, ECG changes, echocardiograms, and cineangiograms in 8 patients with the acute ischemic syndrome who fulfilled the following criteria: 1) no history of previous myocardial infarction, 2) repeated and/or prolonged episodes of chest pain, 3) critical stenosis of the left anterior descending artery with wall motion abnormalities, 4) successful emergency percutaneous transluminal coronary angioplasty, and 5) normal wall motion on repeat cineangiography 4 to 8 weeks later. Creatine kinase (CK) and/or its cardiac isoenzyme (CK-MB) were minimally elevated in all cases. Wall motion was normalized with the reduction of end-systolic volume (end-diastolic volume: from 139 +/- 25 to 140 +/- 37 ml, ns, end-systolic volume: from 68 +/- 16 to 39 +/- 13 ml, p0.001, ejection fraction: from 51 +/- 6 to 71 +/- 6%, p0.001). Serial echocardiograms showed normalization of wall motion within 4 to 28 days. T wave inversion in the left precordial leads developed 30 min to 5 hours after the cessation of chest pain or successful reperfusion, and prominent negative T waves (1.6 +/- 0.6 mV) with QT prolongation (0.56 +/- 0.08 sec) in V3 or V4 reached their peak values within one to 5 days. ECG abnormalities resolved after 21 to 95 days. These ECG findings may indicate reperfusion injury and the presence of myocardial stunning in the anterior wall of the left ventricle.

Thirty-one patients suffering from single vessel exertional angina with collaterals (Group A) were evaluated by stress 201T1 myocardial emission CT (Tl-SPECT) with 16 controls of severely stenotic single vessel exertional angina without collaterals (Group B). Group A included 21 patients (68%) who showed an extensive perfusion defect in double artery myocardial regions, including the normal donor artery myocardial region (DMR). However, there were no such cases in Group B, giving a significant difference between these 2 groups (p less than 0.001). Four patients in Group A, having a perfusion defect both in DMR and in the collateral dependent myocardial region (CMR) underwent a successful percutaneous transluminal coronary angioplasty (PTCA) with disappearance of collaterals. Tl-SPECT findings after PTCA showed no perfusion defect either in CMR or in DMR. This has been explained on the basis that the coronary collaterals stole blood and produced perfusion defect in DMR.

Unexpected displacement of the endotracheal tube during anesthesia caused by postural change of the neck or passive compression by the mouth gag was investigated under transluminal fiberoptic observation. Twenty-two patients were divided into orotracheal and nasotracheal intubation groups according to the technical requirements of the planned oral and maxillofacial surgery. Under nasotracheal intubation, the mean length of displacement from the carina was 21 mm by extension of the neck, and 8 and 7 mm by lateral rotation of the neck to the right and left sides, respectively. Under orotracheal intubation, the mean length of displacement from the carina was 12 mm by extension of the neck and almost 28 mm with application of the mouth gag. To avoid accidental extubation or one-sided bronchial intubation during anesthesia, the tip (distal end) of the endotracheal tube should be located less than 32 mm from the carina before extension of the neck and more than 41 mm from the carina before application of the mouth gag.

A seventy-five-year-old female with general fatigue, high fever and anemia was admitted. Her chest X-ray film revealed pneumonia. She was diagnosed as RAEB-t with the normal karyotype by peripheral blood film and bone marrow aspiration; 125 micrograms/ml of G-CSF was administered s.c. daily in order to increase neutrophil count because of the prolongation of pneumonia. Her blast cells in both peripheral blood and bone marrow showed a remarkable increase by G-CSF. After the cessation of G-CSF administration, blast cells decreased rapidly, and neutrophil count in the peripheral blood increased. Her pneumonia was then cured. After 5 months of stable hematological state, 60% of her bone marrow cells became occupied by blast cells again. So 2 consecutive courses of 14 days p.o. administration of 1,200 mg MST-16/day were tried. Three months after the first MST-16 trial, her bone marrow showed complete remission (CR) which lasted about 4 months. But she died of sepsis after the first relapse. Her bone marrow in CR still revealed several features of dyspoiesis.

The purpose of this study was to evaluate the antihypertensive effect of a new calcium antagonist, clentiazem, on inpatients or outpatients with essential hypertension. After blood pressure was stable and greater than 160/95 mmHg with placebo for at least a 2-week observation period, oral clentiazem was administered once daily and dosage was increased stepwise from 10 to 40 mg over 10 weeks. Blood pressure significantly decreased by the second week of the study, and this hypotensive effect was maintained until the eighth week. Cumulative effective rate (percent of patients whose blood pressure decreased in 20/10 mmHg) in 62 outpatients were as follows; 10.3% at 10 mg, 39.6% at 20 mg, 70.2% at 30 mg, 76.6% at 40 mg. There was no significant postural change observed in the blood pressure from supine to standing position. Side effects such as dizziness, general malaise and gait disturbances were observed in 3 (3.9%) of 76 patients. No abnormal changes in clinical laboratory examinations or electrocardiograms were caused by clentiazem. Thus these data demonstrated that clentiazem produces certain antihypertensive effects with sufficient safety.

Phase I study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate), a derivative of cytosine arabinoside (Ara-C), was conducted by cooperative study groups between January 1986 and June 1987. The dosage for the single and 5-day oral administration ranged 50 to 1,200 and 100 to 900 mg/body/day, respectively. The main adverse effects were myelo-suppression and gastrointestinal toxicities such as nausea, vomiting, anorexia and diarrhea. In the single administration, the maximum tolerated dose (MTD) could not be determined, however, in the 5-day schedule MTD was considered to be 700 to 900 mg/body/day, and the dose limiting factor to be thrombocytopenia. After the single administration (800 mg/body/day) of YNK01, the plasma concentration of Ara-C, an active metabolite of YNK01, was 3.43 ng/ml (Cmax) at 24 hrs. and 0.82 ng/ml at 72 hrs. During the 5-day administration for 300 mg/body/day and 500 mg/body/day, the Ara-C concentration changed from 2.3 to 4.1 ng/ml, and from 1.5 to 11.9 ng/ml respectively, and sustained almost the same concentration as to during the administration period until the 2nd day after the completion of the administration.

Fifteen patients (8 male and 7 female) with multiple myeloma, who were admitted to our hospital between July 1986 and August 1988 and suffering from pain and hypercalcemia, were treated with synthetic calcitonin derivative (elcatonin: ECT). ECT was administered intravenously at a dose of 10-640 units twice daily. Seven patients were treated with ECT (ECT group), and eight patients received combination treatment with ECT and other form of chemotherapy (combination group). With regard to the pain score (PS), significant analgesic effects in both groups were observed during 1-4 week treatments (p less than 0.05). There were no significant differences in PS between two groups. Serum calcium levels in the combination group at 1 and 4 weeks were significantly lower than the initial value (p less than 0.05). Hypocalcemia was not seen in any of the patients. Urinary excretion of calcium at 1 week in ECT group was higher than the initial value (p less than 0.05). The observed toxicities of ECT were slight nausea and vomiting in only 2 patients. These findings suggest that ECT is an useful agent for the treatment of pain and hypercalcemia accompanied with multiple myeloma.

Thirteen patients with gynecologic cancer were treated with ifosfamide (2 g X 5), cisplatin (70 mg/m2) and adriamycin (20 mg/m2) combination chemotherapy. The response rate of 7 evaluable patients was 43%, with a median duration of survival of 14 months. Six patients with non-measurable disease are currently free from disease with a median duration of survival of 18 months. This combination caused reversible myelosuppression. No hemorrhagic cystitis was observed.

Light- and electron-microscopic studies and immunohistochemical procedures were carried out on blood eosinophils and left ventricular endomyocardial biopsies from a 68-year-old man with an eosinophilia of 8.2 X 10(9)/l and congestive cardiac failure due to eosinophilic endomyocardial disease. Some blood eosinophils were vacuolated and degranulated, and reversal of the normal staining pattern of eosinophil granules was seen by means of electron microscopy. The biopsies showed degenerative changes in the cardiac myocytes, with interstitial fibrosis and infiltration by numerous eosinophils, mast cells, and macrophages. Eosinophils infiltrating the myocardium showed a decrease in the number of granules, many of which were indistinct or contained dissolving crystalloids, which occasionally were seen to be discharged onto the surface of adjacent cardiac myocytes. Immunohistochemical studies of the endomyocardial biopsies with a monoclonal antibody, which is specific for activated eosinophils and binds to the secreted forms of eosinophil cationic protein (ECP) and eosinophil protein-X (EP-X), demonstrated that the lesions contained numerous activated eosinophils and secreted ECP and EP-X. These findings support the concept that in eosinophilic endomyocardial disease, activated eosinophils infiltrate and degranulate in the myocardium, releasing eosinophil cationic proteins which then damage adjacent myocardial cells.

Therapeutic effects on cefmenoxime hemihydrochloride (CMX, Bestcall), a new synthetic cephem antibiotic, were examined in the treatment of various infections complicated with hematological diseases. The number of patients treated with CMX was 37 including 5 cases of sepsis or suspected sepsis, 14 cases of pneumonia or suspected pneumonia, 5 cases of upper respiratory diseases, 2 cases of urinary tract infections and 11 cases of other infections. All of these infections were complicated with hematological diseases: Acute leukemia, 13 cases; chronic myelocytic leukemia, 1 case; adult T cell leukemia, 3 cases; malignant lymphoma, 8 cases; Hodgkin's disease, 2 cases and myeloma, 3 cases. CMX were administered by a single intravenous injection or by a drip infusion. The dose was between 2 and 6 grams per day. Good to excellent clinical results were obtained in 25 out of 37 cases, total effective rate of 67.6%. No clinical side effects or abnormal laboratory findings attributable to CMX were observed except for light diarrhea in 2 cases. By the clinical investigation, it was demonstrated that CMX was one of safe and effective antibiotics for treating infections in the compromised hosts complicated with hematological diseases.

In a randomized controlled study, the efficacy of MCNU was compared with that of Busulfan in 95 patients with chronic myelogenous leukemia. Of the patients studied, 95 were entered among whom 77 were evaluable. These comprised 40 for an MCNU group (M) and 37 for a Busulfan group (B). No significant difference was found statistically between the two groups with regard to background factors, i.e., male-to-female ratio, age, white blood cell counts, platelet counts, splenomegaly or Ph1 chromosome.CR rate was 83% for M and 68% for B, and the number of days to CR was 88 for M and 155 for B. Blastic crisis was noted in 31% of M patients and 33% of B patients and the number of days to blastic crisis was 542.6 and 581.9, respectively for the two groups. Deaths accounted for 28% and 29% for each of M and B. Side effects were observed in 31% of M cases and 15% of B cases. A significant difference was observed only in the period to CR. MCNU showed almost equal efficacy to that of Busulfan but was superior to Busulfan in patients who required rapid response. Side effects were mild and transient. Despite its delivery by intravenous injection, the administration of MCNU is deemed convenient, considering the long interval possible between treatments, being comparable in this respect with oral Busulfan. MCNU therefore seems a very effective drug for chronic myelogenous leukemia.

We investigated the natural course of 59 patients with hypertrophic cardiomyopathy (HCM) in follow-up periods of one to 13 years and analyzed the clinical, hemodynamic and echocardiographic parameters to determine the factors influencing the prognosis. Among these patients, 44 (75%) remained stable in a compensated condition with or without medications. Five patients died suddenly and two died of congestive heart failure. Heart failure developed in another eight. At the initial evaluation, these 15 patients had high left ventricular end-diastolic pressure (mean: 22 +/- 8 mmHg) significantly higher than that of 44 compensated patients (mean: 13 +/- 6 mmHg, p less than 0.001). There were no differences in age at the initial evaluation between compensated and end stage groups. Atrial fibrillation occurred persistently in three and transiently in two among ten patients with heart failure during follow-up periods. Ventricular dimensions and systolic function did not statistically differ between the two groups. However, six patients with heart failure had cavity dilatation and deteriolated ventricular contractile function at the initial evaluation. Four of them did not show any change in left ventricular hypertrophy, but the regional thinning of the wall was observed in the remaining two. There were no characteristic features to predict sudden death in the clinical, hemodynamic or echocardiographic parameters. Thus, increased left ventricular end-diastolic pressure, atrial fibrillation, left ventricular dilatation and the regional thinning of the left ventricular wall are useful predictive markers for poor prognosis in HCM.

A phase I-II study of N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine (BH-AC) was conducted by a cooperative study group. In phase I study, a total of 126 patients, 64 of whom had metastatic solid tumors and 62 of whom had leukemia, were administered BH-AC in a single IV dose at day 1 only or in daily IV doses for 3 to 21 days, with dose ranges of 1.5--10.0 mg/kg. Side effects included nausea and vomiting, which were significantly less in incidence and severity than those observed with ara-C. Myelosuppressive toxicity became severe with doses 3.6--5.0 mg/kg per day x 10 days. In phase II study, a total of 37 adult patients with acute leukemia were entered in the study. Responses were noted, with an overall rate of 35% complete remission. Of th 26 patients with AML, there were 13 CR. The recommended schedule of treatment for BH-AC, based on our data, is daily infusion of 4--5 mg/kg over 3 h for approximately 3 weeks. The results with BH-AC in patients with acute leukemia are superior to those which have been reported for ara-C.

One hundred and fifty-two cases with endometrial carcinoma were treated in our clinic between 1973 and 1985. The average age was 55.89 years, and the age range was from 29 to 76 years. Thirty-six cases (23.7%) were nulligravidas and 42 cases (27.6%) were nulliparas. One hundred and ten cases (72.4%) were postmenopausal and the average age at menopause was 49.1 years. The most frequent chief complaint was atypical genital bleeding which was noted in 128 cases (84.2%). The result of a cytologic examination of the uterine cervix was positive in 50.7% and suspicious in 16.9% but results for the endometrium were positive in 63% and suspicious in 21.9%. The cases in this study were classified into 88 cases (57.9%) of T1a, 36 cases (23.7%) of T1b, 12 cases (7.9%) of T2, 3 cases (2.0%) of T3 and 1 case (0.7%) of T4. As to the postoperative diagnosis, there were classified into 86 cases (56.6%) of pT1a, 30 cases (19.7%) of pT1b, 19 cases (12.5%) of pT2, 10 cases (6.6%) of pT3 and 5 cases (3.3%) of pT4. Histopathologically almost all 140 cases (91.41%) were of adenocarcinoma and classified into 88 cases (57.9%) of G1, 39 cases (25.7%) of G2 and 13 cases (8.6%) of G3. The cumulative survival rates after Kaplan-Meier were 95% in pT1a cases, 75.6% in pT1b cases, 67.3% in pT2 cases, 42.2% in pT3 cases and 0% in pT4 cases.

In view of the paucity of reports describing symptoms of increased degree, and deterioration of left ventricular systolic function in patients with apical hypertrophic cardiomyopathy (apical HCM), two cases with congestive heart failure and progressive thinning of previously hypertrophied apical portions of the left ventricle are reported. These were among 13 patients observed from eight to 10 years. Case 1: A 56-year-old man was diagnosed as having apical HCM at the age of 49 years. Severe left ventricular hypertrophy and prominent ST-T changes were observed on ECG during his first admission. His left ventricular end-diastolic pressure (LVEDP) was 24 mmHg and a left ventriculo-gram revealed a decrease in the left ventricular cavity in the apex and marked hypertrophy of the apical wall. Moderate interstitial fibrosis without hypertrophy or disarray of myocytes was observed in a left ventricular endomyocardial biopsy specimen. In two episodes of cardiac arrest he was successfully resuscitated at the age of 50 years. At the age of 55 years, two-dimensional echocardiography revealed thinning and abnormal motion in the apical wall, and a defect in 201T1 accumulation was observed in the same region by perfusion scintigraphy. This patient was readmitted with a diagnosis of cerebral embolism at the age of 56 years. Cardiac catheterization revealed normal LVEDP (8 mmHg), and a left ventriculogram revealed an aneurysm in the left ventricular apex with normal major epicardial coronary arteries. He has been under treatment with antiarrhythmic medications, calcium antagonists and anticoagulants, and has become relatively asymptomatic. Case 2: A 69-year-old-man was diagnosed as having apical HCM after a complete evaluation, including cardiac catheterization, at the age of 59 years. His LVEDP was elevated (17 mmHg), and a left ventricular angiogram revealed marked hypertrophy localized to the apex. Ejection fraction was 64%. A left ventricular endomyocardial biopsy revealed interstitial fibrosis without hypertrophy of myocytes. Thereafter, he has been followed as a New York Heart Association functional class III to IV with occasional elevation of cardiac enzymes but without chest pain or acute changes in his ECGs. However, atrial fibrillation with complete right bundle branch block developed at the age of 60 years. Apical wall thinning and dyskinesis were diagnosed by 2D echocardiography and a defect in the 201T1 accumulation was observed at about 65 years of age. He was readmitted in severe cardiac failure at the age of 69 years, and he was diagnosed as having cardiac asthma with pulmonary capillary wedge pressure of 35 mmHg.(ABSTRACT TRUNCATED AT 400 WORDS)