Effect of colestimide on the concentrations of polychlorinated dibenzo-p-dioxins, polychlorinated dizenzofurans, and polychlorinated biphenyls in blood of Yusho patients.

BACKGROUND: Oral colestimide was reported to lower the concentration of PCDDs, PCDFs, and PCB in the blood of humans. A pilot study showed that the arithmetic mean total TEQ concentrations of PCDDs, PCDFs, and PCBs in the blood of subjects after the trial decreased approximately 20 % compared to pre-trial levels, suggesting that colestimide could decrease human dioxin levels. We designed the current clinical trial study based on this information. In this study, we examined whether colestimide could reduce the individual congener concentrations of PCDDs, PCDFs, and PCBs in the blood of Yusho patients. METHODS: Out of the 36 Yusho patients who participated in the clinical trial, 26 patients self-administered colestimide 3 g/day orally for 6 months. The concentrations of PCDDs, PCDFs and PCBs in the blood of 26 Yusho patients before the trial were compared with those after the trial. RESULTS: The arithmetic mean total TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in the blood of the 26 Yusho patients before and after the clinical trial were 42-303 (mean: 130, median: 120) and 43-283 (mean: 132, median: 118) pg TEQ/g lipid, respectively. The sums of the concentrations of 58 PCB congeners measured in the blood of Yusho patients before and after the trial were 321-2643 (mean: 957, median: 872) and 286-2007 (mean: 975, median: 806) ng/g lipid, respectively, indicating that the concentrations of PCDDs, PCDFs, and PCBs after the trial were almost the same as those before the trial. Among congeners of PCDDs, PCDFs, dioxin-like PCBs, and non-dioxin-like PCBs, most congeners of these compounds did not show a statistically significant decrease after the trial. CONCLUSION: Colestimide may not be beneficial in reducing the high blood levels of dioxin-like compounds in Yusho patients.

[On-the-street DOTS for a homeless tuberculosis patient--case report of a patient who had difficulties with TB treatment adherence].

PURPOSE: A homeless patient with tuberculosis (TB), who had often quit his TB treatment in mid-course and then gone homeless again, succeeded in completing his treatment for over 10 months through on-the-street DOTS ("Bluesky DOTS" is another expression). Based on the analysis of this case, we have discussed how to provide effective countermeasures to non-compliant TB patients. METHOD: An episode of a successful on-the-street DOTS for a 70-year-old homeless man with sputum smear positive pulmonary TB was qualitatively analyzed, with a view toward patient's empowerment. RESULT: The patient had had human-relations problems in his life, and trouble with medical and welfare service staff. During his hospital admissions, he repeatedly self-discharged or was forced to discharge due to violent behavior against staff. Public health nurses at Shinjuku public health center visited the patient frequently at the hospital, and tried to build a good relationship with the patient from the beginning of the treatment. Following a two and half month interruption of the TB treatment after he disappeared from the hospital, he was discovered staying outside at a canal side in the area, and on-the-street TB treatment was carried out, with good cooperation with the hospital and social welfare office. Directly observed TB medication was given to him by a public health nurse and another health center staff member for 293 days, at the park near his living place. The patient often rejected the medication, particularly when he was hungry, but offering lunch to him was a very effective incentive. Through comprehensive supports to the patient, he gradually changed his attitude, and on his own came to consider his health and his future. DISCUSSION: We have analyzed a successfully treated case of a homeless TB patient who had difficulties in maintaining a social life and had not been cooperative in complying with the medication. The level of independence improved during the course of on-the-street DOTS with incentive and other supports. He became receptive to TB treatment and became self-supportive during the course of DOTS, with food as an incentive. This indicates that on-the-street DOTS was successful not only for the treatment completion but also contributed to empowering the TB patient. This approach of adjusting the service to the patient's needs fostered a positive relationship with all stakeholders.

[Inter-laboratory crosscheck study of dioxins and PCBs in human blood samples].

We developed an analytical method for accurately determining the concentrations of dioxin and polychlorinated biphenyls(PCBs) in a blood volume of 5 g. Inter-laboratory crosscheck is available for maintaining the quality of dioxin and PCB analysis. We carried out the crosschecks of dioxin and PCB analysis in the blood with domestic analysis organizations. Two crosschecks each of dioxin and PCB analysis were carried out from 2007 through 2011. As a result, the findings of our analysis accorded well with the analyses of the other organizations. We believe that our analytical method is sufficiently reliable.

The changes in dioxin concentrations in the blood of Yusho patients from 2004 to 2010.

We measured the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) in blood collected from Yusho patients during medical health examinations performed from 2004 to 2010. Out of the 242 and 200 Yusho patients who received medical health examinations in 2004 and 2010, respectively, the concentrations of PCDDs, PCDFs, and PCBs in the blood of 136 patients were measured in both of those years. The concentrations of individual congeners of PCDDs, PCDFs, and PCBs in the blood of these 136 Yusho patients measured in 2004 were compared with those measured in 2010. Among individual congeners of PCDDs, PCDFs, and PCBs, most congeners of these compounds did not significantly decrease from 2004 to 2010. However, the concentrations of 1, 2, 3, 4, 6, 7, 8-heptaCDD, octaCDD, 1, 2, 3, 4, 7, 8-hexaCDF, tetraCB 52/69, pentaCB 101, octaCB 198/201, and octaCB 196/203 in the blood of Yusho patients were significantly decreased from 2004 to 2010. In addition, the concentrations of 1, 2, 3, 6, 7, 8-hexaCDD, 2, 3, 4, 7, 8-pentaCDF, and 1, 2, 3, 6, 7, 8-hexaCDF tended to decrease slightly from 2004 to 2010. These findings suggest that the PCDDs, PCDFs, and PCBs have remained in the blood of Yusho patients for a very long time, with over 40 years having passed since the outbreak of Yusho.

[The difference between male and female dioxin concentrations in the blood of Yusho patients].

In 1968, the contamination of cooking oil by heat-degraded polychlorinated biphenyls (PCBs) caused a case of mass poisoning, the so-called Yusho incident. The cause of Yusho disease is thought to be ingested toxic substances, including not only PCBs but polychlorinated dibenzofuran (PCDFs) in Kanemi rice oil. Extensive studies have been performed since 1995 by the Yusho study group involving follow-up surveys of human blood concentrations of the casual compounds in Yusho patients as well as clinical trials of the acceleration of the excretion of these compounds in Yusho patients. We have previously measured dioxin concentrations in the blood of 649 Yusho patients in annual medical examinations from 2001 to 2009. We determined that the concentrations of 2,3,4,7,8-PeCDF 1,2,3,4,7,8-HxCDF 1,2,3,6,7,8-HxCDF, and 3,3',4,4',5,5'-HxCB (#169) in the blood of Yusho patients were more than twice as high levels to as those of normal controls. In this study, we compared the concentrations of 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF, 1,2,3,6,7,8-HxCDF, and 3,3',4,4',5,5'-HxCB (#169) in the blood of male Yusho patients with those of female Yusho patients. As a result, it was found that the mean concentrations of 2,3,4,7,8-PeCDF 1,2,3,4, 7,8-HxCDF 1,2,3,6,7,8-HxCDF, and 3,3',4,4',5,5'-HxCB (#169) in female Yusho patients were 2.9, 3.7, 2.4, and 1.3 times higher, respectively, than those of male Yusho patients.

[Use of a risk assessment inventory in implementation of the community DOTS in Shinjuku, Japan].

PURPOSES: To investigate the effectiveness of a risk assessment for implementing the DOTS of outpatients in the Japanese city of Shinjuku. SUBJECTS: A total of 435 patients with tuberculosis or latent tuberculosis infection who were registered in the city of Shinjuku between 1 April 2005 and 31 December 2007. METHODS: Soon after their diagnosis or registration and again 4 months thereafter, the patients were interviewed by the public health nurse in charge using a risk assessment inventory that had 17 scales related to the risk of defaulting from the treatment. Based on the results of the risk assessment, the patients were provided with an appropriately adapted DOTS. RESULTS: Out of all patients, 386 (88.7%) were assessed twice, of whom 338 (77.7%) were those with active disease. The patients were classified into three groups according to their risk scales: high-, medium-, and low-risk groups. There was no change in the risk grouping during the 4 months in 307 (90.8%) patients. However, in 12 patients (3.6%) the risk level was increased after 4 months, because of the development of side effects and problems with regular outpatient visits. The common methods of support in drug taking were daily DOT at the health center for patients in the high-risk group, and DOT at pharmacy shops once or twice weekly with self-medication on the other days for patients in the medium-risk group. For the low-risk group, the public health nurses made interview once or twice a month. There was no significant difference in the treatment success rate, default rate, or mortality rate among these three groups. DISCUSSION: The treatment outcome suggests that the community DOTS in this area may be effective. It was important to assess possible risks in treatment for each patient in order to identify the support needs and means. Also, it is necessary to develop a good risk assessment inventory scale.

[Tuberculosis control in Shinjuku Ward, Tokyo--promoting the DOTS program and its outcome].

OBJECTIVES: The objectives were to report how to promote tuberculosis (TB) control including DOTS (Directly Observed Treatment, Short-course) programs, and to evaluate the results of TB control programs in Shinjuku Ward (Shinjuku-ku). SETTING AND CHARACTERISTICS: Inhabitants and TB patients in Shinjuku Ward. Shinjuku Ward is located in the center of metropolitan Tokyo and has typical urban TB problems, such as high incidence rate and TB among foreigners and the homeless. The TB incidence rates in Shinjuku Ward decreased from 83.9 per 100,000 population in 1999 to 42.5 per 100,000 population in 2006, however, the rates were still two times higher than the national average. Therefore, one of the important TB programs in Shinjuku has been to actively detect cases among high-risk groups such as foreigners and the homeless. METHODS: We observed the trend of case detection rates by health examination with chest X-ray among different high-risk groups, and compared the treatment outcomes before and after DOTS program execution. We also reviewed the changes of re-treatment rates and drug resistance rates. RESULTS: The case detection rates of TB by health examinations of foreign students at Japanese language schools decreased from 0.49% in 1996 to 0.13% in 2006 (p = 0.021). Although the case detection rates decreased, they were still about 26 times higher than those of Japanese students. While, the case detection rates among the homeless remained high with 4.7%, 3.3%, 4.5% and 3.6% in 1999-2002, respectively, since 2003, however, they had decreased and no TB cases were detected in 2005-2006. The DOTS program for homeless TB patients has been carried out since 2000 and that for the foreigners since 2003. The rates of defaulting during treatment before DOTS were very high among both homeless patients (21.4%) and foreigners (29.8%) in 1998-1999. However, after the introduction of DOTS program, those rates declined to 10.4% (p = 0.014) among the homeless and 7.8% (p = 0.002) among foreigners in 2002-2004. The proportion of newly notified patients with previous TB treatment and those with multi-drug resistant TB (MDR-TB) have also decreased after the introduction of DOTS programs. From 2000-2002 to 2003-2006, the re-treatment rates decreased from 19.4% to 10.0% (p < 0.001) and MDR-TB rates decreased from 1.6% to 0.2% (p = 0.042), respectively. DISCUSSION: The key points of TB control in Shinjuku Ward are to detect TB cases early especially among the high-risk groups, and to assist all TB patients to complete their treatment. In order to expand this strategy, besides promoting active case findings among high-risk groups, we have developed many types of DOTS programs, considering each patient's lifestyle and cooperating with school teachers at schools, pharmacists at pharmacies, home-care specialists at homes or facilities for the elderly, and so on. Among others, a major premise for the homeless and some other socially disadvantaged patients was to guarantee the provision of medicine and living by introducing social welfare services, before starting DOTS programs. This approach might have helped to reduce the defaulting rate, relapse rate and MDR-TB rate.

[Trend of 2,3,4,7,8-PeCDF concentrations in the blood of Yusho patients over four years].

In the Yusho medical checkup, measurement of dioxin has been performed since 2001. Although the time trend of dioxin concentrations in blood from 2001 to 2005 has been reported for the whole measurement candidate, details in the trend are not known. Therefore, to verify the trend, we divided the Yusho patients into four quatertile groups based on the dioxin concentrations. About 39 years have passed since Yusho occurred, and it is said that a big change in the concentrations of 2,3,4,7,8-PeCDF in blood is now no longer seen. However, when the Yusho patients were divided into the four groups, a downward tendency was even now found in the higher dioxin groups, but not in the lower dioxin groups.