Cheol-In Yoo

Dopamine transporter density is decreased in parkinsonian patients with a history of manganese exposure: What does it mean?

Manganese (Mn) exposure can cause parkinsonism. Pathological changes occur mostly in the pallidum and striatum. Two patients with a long history of occupational Mn exposure presented with Mn‐induced parkinsonism. In one patient, magnetic resonance imaging (MRI) showed findings consistent with Mn exposure, and Mn concentration was increased in the blood and urine. However, this patients clinical features were typical of idiopathic Parkinson disease (PD). Previous pathological and positron emission tomography studies indicate that striatal dopamine transporter density is normal in Mn‐induced parkinsonism, whereas it is decreased in PD. Therefore, we performed [123I]‐(1r)‐2β‐carboxymethoxy‐3β‐(4‐iodophenyl)tropane ([123I]‐β‐CIT) single‐photon emission computed tomography. Severe reduction of striatal β‐CIT binding was indicated, which is consistent with PD. We propose three interpretations: (1) the patients have PD, and Mn exposure is incidental; (2) Mn induces selective degeneration of presynaptic dopaminergic nerve terminals, thereby causing parkinsonism; or (3) Mn exposure acts as a risk of PD in these patients. Our results and careful review of previous studies indicate that the axiom that Mn causes parkinsonism by pallidal lesion may be over‐simplified; Mn exposure and parkinsonism may be more complex than previously thought. Further studies are required to elucidate the relationship between Mn and various forms of parkinsonism.

Whole blood manganese correlates with high signal intensities on T1-weighted MRI in patients with liver cirrhosis.

We examined whole blood (MnB), plasma (MnP) and urinary Mn (MnU) concentrations in 33 cirrhotics and 11 healthy controls to clarify: (1) whether, in chronic liver diseases, MnB or MnP reflects pallidal signal intensities in magnetic resonance imaging (MRI); and (2) which factors in chronic liver diseases correlate with pallidal signal intensities in T1-weighted MRI. Increased signal intensity in the pallidum was observed in 27 (81.8%) of 33 patients with liver cirrhosis in T1-weighted MRI. There was a significant correlation between MnB and pallidal index (PI) (gamma = 0.559, P < 0.01) in the patients. However, no significant correlation was observed between MnP and PI (gamma = 0.353, P > 0.05). According to a multiple linear regression, MnB reflected the signal intensities of T1-weighted MRI better than MnP or MnU. Child/Pugh score and total bilirubin level also correlated with PI. However, the hemoglobin level did not correlate with PI significantly.

Phase II study of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib.

Background:This prospective, phase II trial evaluated the efficacy and safety of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours (GISTs) after failure of at least imatinib and sunitinib.Methods:Patients received oral dovitinib, 500 mg once daily, for 5 consecutive days, followed by a 2-day rest, every 28 days. The primary endpoint was disease control rate (DCR; objective response+stable disease (SD)) at 24 weeks, assessed by computed tomography (CT) scan according to RECIST v1.0. Metabolic response was evaluated by positron emission tomography (PET)–CT scans performed at baseline and after 4 weeks of treatment.Results:Between September 2011 and April 2012, 30 patients were enroled. DCR at 24 weeks by RECIST v1.0 was 13% and one patient (3%) had a partial response. Based on the European Organization for Research and Treatment of Cancer PET response criteria, four patients (13%) had a metabolic partial response after 4 weeks of treatment. At a median follow-up of 8.3 months (range, 6.3–12.2 months), median progression-free survival (PFS) was 3.6 months (95% confidence interval (CI), 3.5–3.7 months) and median overall survival was 9.7 months (95% CI, 6.0–13.4 months). Metabolic progressive disease at Week 4 was significantly associated with shorter PFS (P=0.03). Grade 3/4 adverse events included asthenia (20%), neutropenia (13%), thrombocytopenia (10%), and hypertriglyceridaemia (10%). Most toxicities were manageable by dose modification.Conclusion:Dovitinib showed modest antitumour activity with manageable toxicities in heavily pretreated patients with advanced GISTs.

Effect of manganese exposure on MPTP neurotoxicities.

We used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model to evaluate whether manganese (Mn) exposure can affect MPTP-induced neurotoxicity. We randomly assigned adult male C57BL/6 mice (n=5-7 per group) the following treatments: SO, Mn(-) x MPTP(-); MO, Mn(+) x MPTP(-); SM, Mn(-) x MPTP(+); MM, Mn(+) x MPTP(+). Mn (MnCl(2).4H(2)O) was administered intraperitoneally at a dose of 2 mg/kg daily for 3 weeks. MPTP was then administered intraperitoneally at a dose of 30 mg/kg daily for 5 days in the SM and MM groups. Seven days after the last MPTP injection, the animals were sacrificed. Blood Mn levels were elevated in the Mn-exposed groups. Striatal Mn levels were not influenced by Mn treatment alone, however, they were decreased following MPTP. Tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in the substantia nigra pars compacta (SNpc) were decreased significantly in the MPTP-exposed groups. Densities of TH- and dopamine transporter (DAT)-ir axon terminals in the caudate-putamen (CPU) were also decreased in the MPTP-treated groups. Furthermore, glial fibrillary acidic protein (GFAP)-ir astrocytes increased in the CPU with MPTP treatment. However, no effects were observed with Mn exposure. Concentrations of dopamine (DA), 3,4-dihydrophenyl acetic acid (DOPAC) and homovanillic acid (HVA) in the corpus striatum were also decreased significantly with MPTP treatment alone, but Mn had no effect. Thus, decreased dopaminergic activities with MPTP led to decreased DA and its metabolites. Significant hypertrophies of GFAP-ir astrocytes in the globus pallidus (GP) were observed in Mn-exposed groups, especially in the MM group. MPTP targeted dopaminergic systems whereas Mn neurotoxicities occurred in the GP. In conclusion, our data suggest that Mn does not potentiate the neurotoxicity of MPTP.

Whole Blood and Red Blood Cell Manganese Reflected Signal Intensities of T1-Weighted Magnetic Resonance Images better than Plasma Manganese in Liver Cirrhotics

Whole Blood and Red Blood Cell Manganese Reflected Signal Intensities of T1‐Weighted Magnetic Resonance Images better than Plasma Manganese in Liver Cirrhotics: Younghee Choi, et al. Department of Occupational and Environmental Medicine, Ulsan University Hospital, South Korea—We examined whole blood (MnB), red blood cell (MnRBC), plasma (MnP) and urinary Mn (MnU) concentrations in 22 liver cirrhotics and 10 healthy controls to evaluate Mn concentration in which a fraction of biological samples best reflects pallidal signal intensities (pallidal index; PI) on T1‐weighted magnetic resonance images (MRI) in liver cirrhotics. Increased signal intensity in the globus pallidus was observed in 18 (81.8%) of the 22 patients with liver cirrhosis. In a transplanted patient, increased pallidal signals also resolved as his liver function tests normalized after liver transplantation. There were significant correlations between MnB/MnRBC and PI (ρ=0.529, ρ=0.573, respectively) in liver cirrhotics, although no significant correlation was observed between MnP/MnU and PI. According to a multiple linear regression, MnB and MnRBC reflected the signal intensities of T1‐weighted MRI better than MnP or MnU.

Metabolic syndrome, lifestyle risk factors, and distal colon adenoma: A retrospective cohort study

AIM To investigate relationships between colorectal adenoma incidence, metabolic syndrome (MS) components and lifestyle factors. METHODS We conducted a retrospective cohort study using data from individuals who had multiple sigmoidoscopies for colon cancer at the Health Promotion Center of Ulsan University Hospital in Korea from 1998 to 2007. RESULTS By multivariate analysis, the incidence of distal colon adenoma was increased by more than 1.76 times in individuals with at least one component of MS compared to those without a component of MS. After adjustment for age, gender, smoking, drinking, and physical exercise, only high body mass index (BMI) was significantly associated with the incidence of distal colon adenoma (Hazard ratio 1.66, 95% confidence interval 1.05-2.62). CONCLUSION Our results suggest that high BMI may increase the risk of colorectal adenoma in Korean adults.

Calcification Mimicking Manganese-Induced Increased Signal Intensities in T1-Weighted MR Images in a Patient Taking Herbal Medicine: Case Report

Characteristic high signal intensities confined to the globus pallidus on T1-weighted magnetic resonance image (MRI) can be observed in manganese (Mn)-exposed workers, however, these high signals should be differentiated from those due to other causes such as fat, hemoglobin breakdown products, melanoma, neurofibromatosis, and calcification. A 39-year-old woman was admitted with mutism and involuntary movements which had developed the day before. She had ingested two packs of liquid herbal medicine containing 0.53 mg of Mn daily for 4 months prior to visiting our hospital. Her MRI showed high signals, confined mainly to the globus pallidus on T1-weighted images. Follow-up brain MRI at an interval of 11 months showed no interval change. Brain computed tomography (CT) at the time of the second MRI showed symmetric calcification on both globus pallidus. Blood levels of liver function tests, calcium, phosphorus, and parathyroid hormone were within normal ranges. The increased signals, which were first presumed to be induced by Mn, were concluded to be due to calcification based on the following reasons. First, follow-up brain MRI at an interval of 11 months did not show any interval change. Second, the ingested amount of 1.06 mg Mn daily for 4 months is even less than that added to mineral supplements for adults. Third, Mn-induced high signals in T1-weighted MRI do not show any abnormal findings in brain CT. The present case report suggests that brain CT should be performed to rule out symmetric calcification on basal ganglia in patients showing increased signals in T1-weighted MRI, but who do not have a significant exposure history to Mn. The present report also showed that the amount of 1.06 mg Mn daily ingested for 4 months did not cause the high signal in brain MRI.

Measuring Health Related Quality of Life of General Adult Population in One Metropolitan City using EQ-5D

Measurements of health related quality of life can be used to compare patients with specific conditions to average individuals in the general population in a similar age and gender group. However there are few data available regarding health related quality of life for the general population of Korea. Therefore, this study was conducted to examine the validity of the Korean version of EQ-5D and to measure the health related quality of life of the general adult population in a metropolitan city. The survey was cross-sectional and employed a stratified and multistage sampling design through 100 examination sites in 5 districts of UIsan. A total of 12,644 individuals from 4,112 households participated in the survey. Of these, we analyzed data from 8,068 adults who were over 19 years old and completed the EQ-5D. To examine the validity of the questionnaire, the differences in 5 dimensions and the were analyzed with regard to demographic and socioeconomic factors such as sex, age, income, and education. In addition, visual analogue scales (VAS) were used to evaluate the overall health related quality of life issues of the respondents. The level of health related quality of life of the general adult population was then compared with the results from the third Korean National Health and Nutrition Examination Survey and other countries. There were a small number of people with problems related tomobility, self-care, and usual activity. In addition, many people complained ofpain/discomfort and anxiety/depression. The complaint rate in each dimension, VAS, and indicated relatively better states for males, the younger group, the higher income group, and the higher education group. In addition, the level of health related quality of life of the general population of Ulsan was relatively higher than that of Koreans nationwide as well as the populations of other countries. EQ-SD provided a valid measure of the health-related quality of life of the general adult population. In addition, the results of a survey of Ulsan revealed that the quality of life of its population is better than that of the overall population of Korea and of the populations of other countries.

The Levels of Blood Lead and Cadmium in Urban and Rural Population in Korea

The purpose of this study was to evaluate the levels of blood lead and cadmium in urban and rural populations. Blood samples were collected from 100 urban (Busan) residents and 150 rural residents (Jinju-84, Gijang-66) from July 1 to August 30, 2007. The blood lead and cadmium levels were analyzed using flameless atomic absorption spectrophotometry and were compared by age, gender and smoking status. The mean levels of blood lead in urban-Busan, rural-Jinju and rural-Gijang residents were , and , respectively. There was a significant difference in the level of blood lead between urban-Busan residents and rural-Gijang residents. The mean levels of blood cadmium in urban-Busan, rural-Jinju and rural-Gijang residents were , and , respectively. There was a significant difference in the level of blood cadmium between urban-Busan residents and rural-Jinju residents. This study showed that the levels of blood lead and cadmium were significantly different between urban and rural populations. The level of blood lead was highest in urban-Busan residents, but the level of blood cadmium was highest in rural-Jinju residents. Further studies are needed to define the cause of high levels of blood lead and cadmium related to area of residence and personal habits.

MONW phenotype is associated with advanced colorectal adenoma in Korean men.

The aim of this study was to investigate whether there was a relationship between colorectal adenoma and metabolically obese but normal weight (MONW) among Korean men and women. The MONW phenotype is defined as a BMI <25, but fulfilling the metabolic syndrome (MS) criteria with a modified waist circumference (≥90 cm for men and ≥85 cm for women) appropriate for Korean. A total of 3,430 subjects (2,263 men and 1,167 women; 23–75 years old) were included in the study. Colorectal adenomas were diagnosed in 775 men and 199 women. The rate of advanced adenomas in males was 24.3% and in females 21.1%. A significant association between MONW and advanced colorectal adenoma was found in men (age‐adjusted odds ratio (OR) = 1.92, 95% confidence interval (CI): 1.06–3.47) but not in women (age‐adjusted OR = 1.80, 95% CI: 0.50–6.45). The findings suggest that men with MONW may have an increased risk of developing advanced colorectal adenoma whereas this does not seem true for females.