Improved diagnostic performance of susceptibility-weighted imaging with compressed sensing-sensitivity encoding and neuromelanin-sensitive MRI for Parkinson's disease and atypical Parkinsonism.

AIM: To verify the diagnostic performance of the loss of nigrosome-1 on susceptibility-weighted imaging (SWI) with compressed sensing-sensitivity encoding (CS-SENSE) and neuromelanin on neuromelanin-sensitive (NM) magnetic resonance imaging (MRI) for the diagnosis of Parkinson's disease (PD) and atypical Parkinsonism. MATERIALS AND METHODS: A total of 195 patients who underwent MRI between October 2019 and February 2020, including SWI, with or without CS-SENSE, and NM-MRI, were reviewed retrospectively. Two neuroradiologists assessed the loss of nigrosome-1 on SWI and neuromelanin on the NM-MRI. The result of N-3-fluoropropyl-2-beta-carbomethoxy-3-beta-(4-iodophenyl) nortropane positron-emission tomography (PET) was set as the reference standard. RESULTS: When CS-SENSE was applied for nigrosome-1 imaging on SWI, the non-diagnostic scan rate was lowered significantly from 19.3% (17/88) to 5.6% (6/107; p=0.004). Diagnosis of PD and atypical Parkinsonism based on the loss of nigrosome-1 on SWI and based on NM-MRI showed good diagnostic value (area under the curve [AUC] 0.821, 95% confidence interval [CI] = 0.755-0.875: AUC 0.832, 95% CI = 0.771-0.882, respectively) with a substantial inter-reader agreement (κ = 0.791 and 0.681, respectively). Combined SWI and neuromelanin had a similar discriminatory ability (AUC 0.830, 95% CI = 0.770-0.880). Similarly, the diagnosis of PD was excellent. CONCLUSIONS: CS-SENSE may add value to the diagnostic capability of nigrosome-1 on SWI to reduce the nondiagnostic scan rates. Furthermore, loss of nigrosome-1 on SWI or volume loss of neuromelanin on NM-MRI may be helpful for diagnosing PD.

Efficacy and safety of shunt surgery in patients with idiopathic normal-pressure hydrocephalus: can we predict shunt response by preoperative magnetic resonance imaging (MRI)?

AIM: The aim of this study was to identify preoperative magnetic resonance imaging (MRI) findings that can predict the shunt responsiveness in idiopathic normal-pressure hydrocephalus (iNPH) patients and to investigate postoperative outcome and complications. MATERIALS AND METHODS: A total of 192 patients with iNPH who underwent shunt at our hospital between 2000 and 2021 were included to investigate complications. Of these, after exclusion, 127 (1-month postoperative follow-up) and 77 (1-year postoperative follow-up) patients were evaluated. The preoperative MRI features (the presence of tightness of the high-convexity subarachnoid space, Sylvian fissure enlargement, Evans' index, and callosal angle) of the shunt-response and nonresponse groups were compared, and a systematic review was conducted to evaluate whether preoperative MRI findings could predict shunt response. RESULTS: Postoperative complications within one month after surgery were observed in 6.8% (13/192), and the most common complication was hemorrhage. Changes in corpus callosum were observed in 4.2% (8/192). The shunt-response rates were 83.5% (106/127) in the 1-month follow-up group and 70.1% (54/77) in 1-year follow-up group. In the logistic regression analysis, only Evans' index measuring >0.4 had a significant negative relationship with shunt response at 1-month follow-up; however, no significant relationship was observed at 1-year follow-up. According to our systematic review, it is still controversial whether preoperative MRI findings could predict shunt response. CONCLUSION: Evans' index measure of >0.4 had a significant relationship with the shunt response in the 1-month follow-up group. In systematic reviews, there is ongoing debate about whether preoperative MRI findings can accurately predict responses to shunt surgery. Postoperative corpus callosal change was observed in 4.2% of iNPH patients.

Detection rate of MR myelography without intrathecal gadolinium in patients with newly diagnosed spontaneous intracranial hypotension.

AIM: To evaluate the detection rate of magnetic resonance (MR) myelography without intrathecal gadolinium for cerebrospinal fluid (CSF) leakage in patients with newly diagnosed spontaneous intracranial hypotension (SIH) and to validate a published scoring system for predicting CSF leakage. MATERIALS AND METHODS: This retrospective, observational, single-institution study included patients with newly diagnosed SIH between March 2015 and April 2021. Patients were included if they (a) had newly diagnosed SIH and (b) underwent initial brain MR imaging and preprocedural MR myelography with two- and three-dimensional turbo spin-echo sequences. Patients who underwent spine surgery or procedures including epidural injection and acupuncture were excluded. The detection rate was defined as the proportion of patients with a true-positive MR myelography result among all patients with confirmed CSF leakage. The interobserver agreement for the MR myelography results between two radiologists was analysed using weighted kappa statistics. RESULTS: A total of 136 patients (mean age, 48 years; 70 women) with suspected SIH were included. Of these patients, 120 (88%, 120/136) were confirmed to have CSF leakage. Of the patients with confirmed CSF leakage, 90 (75%, 90/120) had epidural fluid collection. The detection rate of MR myelography for CSF leakage was 88% (105/120). The interobserver agreement between the two readers for detecting CSF leakage (κ = 0.76) or epidural fluid collection (κ = 0.76) on MR myelography was high. Among 24 patients with normal brain MR imaging results, 16 had CSF leakage (67%, 16/24). CONCLUSIONS: Non-invasive MR myelography without intrathecal gadolinium should be considered to detect CSF leakage in patients with suspected SIH.

Cognitive anosognosia is associated with frontal dysfunction and lower depression in Parkinson's disease.

BACKGROUND AND PURPOSE: Anosognosia refers to a deficit of self-awareness or impaired insight for cognitive and behavioral problems. Cognitive anosognosia was explored in de novo patients with Parkinson's disease (PD) and its relationship to cognitive function and neuropsychiatric symptoms was investigated. METHODS: The cross-sectional study enrolled 340 drug-naïve patients with PD. According to the presence of mild cognitive impairment (MCI) and subjective cognitive complaint, patients were classified as patients with cognitive anosognosia (PD-CA, n = 74), with normal cognitive recognition (PD-NR, n = 184) or with cognitive underestimation (PD-CU, n = 82). After controlling for covariates, cognitive performance and neuropsychiatric symptoms were compared between the PD groups. RESULTS: Cognitive anosognosia was found in 21.8% of patients with de novo PD. The PD-CA group showed poorer performance in all cognitive domains except for attention. Amongst PD patients with MCI, those with cognitive anosognosia showed lower composite z-scores in the Stroop color reading test than those without. The Beck Depression Inventory score in the PD-NR group was lower than that in the PD-CU group and higher than that in the PD-CA group. The Cognitive Complaints Interview score mediated the association between cognitive anosognosia and Beck Depression Inventory score. CONCLUSIONS: Cognitive anosognosia in PD was associated with greater frontal dysfunction and lower depression. Since cognitive anosognosia has a harmful impact on PD patients and their caregivers due to overestimation of their abilities in everyday life, early identification of cognitive anosognosia in PD is important in management and prognosis.

Sex-dependent association of urate on the patterns of striatal dopamine depletion in Parkinson's disease.

BACKGROUND AND PURPOSE: The aim was to investigate the relationship between the serum urate (UA) levels and patterns of striatal dopamine depletion in patients with de novo Parkinson's disease (PD). METHODS: In all, 167 de novo PD patients who underwent 18 F-fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane positron emission tomography scans were enrolled. After quantifying dopamine transporter (DAT) availability in each striatal subregion, sex-dependent patterns of striatal dopamine depletion were analysed by measuring (i) dopamine depletion in the other striatal subregions and posterior putamen (intersubregional ratio, ISR) and (ii) the interhemispheric asymmetry of dopamine depletion in the posterior putamen (asymmetric ratio, AR). RESULTS: The interaction analysis revealed a significant interaction effect of sex and serum UA levels on the ISR but not on the AR. The ISR was negatively correlated with the serum UA levels in all patients with PD (r = -0.156, P = 0.045), and this association was more prominent in male PD patients (r = -0.422, P < 0.001). However, no significant association between the AR and serum UA levels was found in any of the patients. In addition, serum UA levels were significantly associated with DAT availability in the posterior putamen on both the more affected side (r = 0.312, P = 0.005) and the less affected side (r = 0.312, P = 0.005) only in male PD patients. CONCLUSIONS: The present study demonstrated the potentially close sex-specific relationship between the serum UA levels and the anterior-posterior gradient of DAT patterns, suggesting a sex-specific protective effect of UA on nigrostriatal dopaminergic neurons in de novo PD.

Sex-specific association of urate and levodopa-induced dyskinesia in Parkinson's disease.

BACKGROUND AND PURPOSE: As a major antioxidant, uric acid (UA) is known to be associated with the clinical progression of Parkinson's disease (PD). This study investigated whether baseline UA levels are associated with the risk for levodopa-induced dyskinesia (LID) in PD in a sex-dependent manner. METHODS: In all, 152 patients with de novo PD (78 males and 74 females) who were followed up for >2 years were enrolled. The effect of baseline serum UA levels on LID-free survival was assessed by Cox regression, separately for sex, whilst being adjusted for potential confounding factors. The optimal UA level cut-off value to determine the high-risk group for LID was set using Contal and O'Quigley's method. RESULTS: Levodopa-induced dyskinesia developed in 23 (29.5%) male patients and 30 (40.5%) female patients. Cox regression showed a significant interaction between UA level and sex. Higher UA levels were associated with a higher risk for LID in male PD patients (hazard ratio 1.380; 95% confidence interval 1.038-1.835; P = 0.027), although this relationship was not observed in female PD patients. The optimal UA level cut-off for LID in male PD was 7.2 mg/dl, and the high UA group had a 5.7-fold higher risk of developing LID than the low UA group. CONCLUSIONS: Contrary to a presumptive beneficial role of UA, the present study demonstrated that higher UA levels are associated with increased risk of LID occurrence in male patients with PD, suggesting a sex-dependent role of UA in LID.

Effects of Alzheimer's disease and Lewy body disease on subcortical atrophy.

BACKGROUND AND PURPOSE: Subcortical structures are affected by neurodegeneration in Alzheimer's disease (AD) and Lewy body disease (LBD). Although the co-occurrence of AD and LBD pathologies and their possible interaction have been reported, the effect of AD and LBD on subcortical structures remains unknown. The effects of AD and LBD on subcortical atrophy and their relationship with cognitive dysfunction were investigated. METHODS: The cross-sectional study recruited 42 patients with pure AD related cognitive impairment (ADCI), 30 patients with pure LBD related cognitive impairment (LBCI), 58 patients with mixed ADCI and LBCI, and 29 normal subjects. A general linear model was used to compare subcortical volume and shape amongst the groups, to investigate the independent and interaction effects of ADCI and LBCI on subcortical shape and volume, and to analyze the relationship between subcortical volume and cognitive dysfunction in each group. RESULTS: Alzheimer's disease related cognitive impairment and LBCI were independently associated with subcortical atrophies in the hippocampus and amygdala and in the hippocampus and putamen respectively, but their interaction effect was not significant. Compared to the control group, the pure LBCI group exhibited additional local atrophies in the amygdala, caudate and thalamus. Subcortical atrophies correlated differently with cognitive dysfunction according to the underlying causes of cognitive dysfunction. CONCLUSIONS: The patterns of subcortical atrophies and their correlation with cognitive dysfunction differ according to the underlying AD, LBD or concomitant AD and LBD.

Impact of formulary interventions on the minimum inhibitory concentration of methicillin-resistant Staphylococcus aureus to mupirocin, chlorhexidine, and octenidine in a Singapore tertiary institution.

Methicillin-resistant Staphylococcus aureus (MRSA) decolonization is an effective measure to prevent clinical infection but resistance is a concern. We aim to evaluate the impact of mupirocin (MUP) ointment formulary removal, plateauing use of chlorhexidine gluconate (CHG), and hospital-wide introduction of octenidine (OCT)-based products on the minimum inhibitory concentration (MIC) of MRSA to MUP, CHG, and OCT in our hospital. A prevalence study was conducted at three time points (TP) on consecutive MRSA screening isolates to evaluate for their MICs to MUP, CHG, and OCT using broth microdilution sensititre plates and detection of the ileS-2 gene encoding high-level MUP resistance in 2013 (pre-intervention TP1; n = 160), 2016 (early post-intervention TP2; n = 99) and 2017 (late post-intervention TP3; n = 76). Statistical analyses were performed using Chi square test with reference from TP1. There was a significant improvement in MUP susceptibility (MIC < 4 mcg/ml) from 71.9% (TP1) to 86.9% (TP2; p = 0.006) to 88.2% (TP3; p = 0.007). The prevalence of MUP high-level resistance (MIC > 256 mcg/ml) reduced from 25.0% (TP1) to 12.1% (TP2; p = 0.014) to 5.3% (TP3; p = 0.001). Likewise, the prevalence of isolates harboring the ileS-2 gene decreased from 28.1% (TP1) to 18.2% (TP2; p = 0.072) to 9.2% (TP3; p = 0.002). OCT MIC range remains stable at 0.5 to 1 mcg/ml across all three TPs. The proportion of isolates with reduced CHG susceptibility (MIC ≥ 4 mcg/ml) increased over the three TPs from 23.1 to 27.2% (p = 0.45) to 42.1% (p = 0.003). Active formulary regulations have an impact on the resistance profile of MRSA and can be used as a strategy to preserve the MRSA decolonization armamentarium.

Clinical relevance of amnestic versus non-amnestic mild cognitive impairment subtyping in Parkinson's disease.

BACKGROUND AND PURPOSE: To clarify whether subtyping of amnestic and non-amnestic mild cognitive impairment (MCI) is clinically relevant in Parkinson's disease (PD) by analyzing patterns of neuroimaging and longitudinal cognitive changes. METHODS: We performed comparative analyses of cortical thickness, hippocampal volume, white matter integrity and resting-state functional connectivity between the patients with de-novo PD with amnestic MCI (PD-aMCI) (n = 50) and non-amnestic MCI (PD-naMCI) (n = 50) subtypes. Additionally, we assessed the longitudinal rate of cognitive decline in each cognitive domain over time and the rate of dementia conversion in patients with de-novo PD-aMCI (n = 125) and PD-naMCI (n = 61). RESULTS: The demographic data showed that scores in memory domains were lower in the PD-aMCI group compared with the PD-naMCI group. There were no significant differences in cortical thickness, hippocampal volume and white matter integrity between the two groups, although the PD-aMCI group exhibited more cortical thinning and hippocampal atrophy relative to the control group. The PD-aMCI group exhibited increased functional connectivity in the left posterior parietal region with the salience network relative to the PD-naMCI group. The longitudinal cognitive assessment demonstrated that patients with PD-aMCI exhibited a more rapid cognitive decline in frontal/executive function than those with PD-naMCI (P = 0.022). In addition, the PD-aMCI group had a higher risk of dementia conversion than the PD-naMCI group. CONCLUSIONS: This study suggests that the designation of PD-MCI subtypes based on memory function would highlight the heterogeneity of functional correlates as well as the longitudinal cognitive prognosis.

Rapid eye movement sleep behaviour disorder and striatal dopamine depletion in patients with Parkinson's disease.

BACKGROUND AND PURPOSE: Rapid eye movement sleep behaviour disorder (RBD) is related to striatal dopamine depletion. This study was performed to confirm whether clinically probable RBD (cpRBD) in patients with Parkinson's disease (PD) is associated with a specific pattern of striatal dopamine depletion. METHODS: A prospective survey was conducted using the RBD Screening Questionnaire (RBDSQ) in 122 patients with PD who had undergone dopamine transporter (DAT) positron emission tomography scan. RESULTS: Patients with cpRBD (RBDSQ ≥ 7) exhibited greater motor deficits, predominantly in the less-affected side and axial symptoms, and were prescribed higher levodopa-equivalent doses at follow-up than those without cpRBD (RBDSQ ≤ 4), despite their similar disease and treatment durations. Compared to patients without cpRBD, those with cpRBD showed lower DAT activities in the putamen, particularly in the less-affected side in all putaminal subregions, and a tendency to be lower in the ventral striatum. In addition, greater motor deficits in patients with cpRBD than in those without cpRBD remained significant after controlling for DAT binding in the putamen and other confounding variables. CONCLUSIONS: These results demonstrated that the presence of RBD in patients with PD is associated with different patterns of both motor deficit distribution and striatal DAT depletion, suggesting that the presence of RBD represents a distinct PD subtype with a malignant motor parkinsonism.

Volumetric analysis of the cerebellum in patients with progressive supranuclear palsy.

BACKGROUND AND PURPOSE: Although early cerebellar symptoms are one of the exclusive criteria in the diagnosis of progressive supranuclear palsy (PSP), cerebellar involvement in PSP is evident both clinically and pathologically. However, structural analysis focusing on the cerebellum has not been previously studied in patients with PSP. We aimed to evaluate cerebellar involvement in PSP using a magnetic resonance imaging-based segmental volumetric analysis. METHODS: We retrospectively enrolled 48 patients with PSP composed of 25 patients with PSP-Richardson's syndrome (RS) and 23 patients with pure akinesia with gait freezing, 39 patients with Parkinson's disease (PD) and 34 healthy controls. Data on both the whole and segmented cerebellar volumes were analyzed using a fully automated procedure. RESULTS: A general linear model showed that whole cerebellar volume in patients with PSP was significantly smaller compared with that of patients with PD or controls after controlling for age, sex and intracranial volume (P = 0.34). In addition, patients with PSP exhibited decreased regional volume in the crus I, lobule VIIIa and lobule VIIIb, which play roles as secondary representations of motor tasks, compared with patients with PD or controls. In subgroup analysis of PSP, volume loss in the whole and segmental cerebellum was more pronounced in patients with PSP-RS than in those with pure akinesia with gait freezing, PD or control subjects. CONCLUSION: These data demonstrate that cerebellar atrophy is evident in patients with PSP and is especially prominent in the PSP-RS group. These findings increase understanding of the clinicopathological basis of cerebellar involvement in PSP.

Recurrent trichosporonosis with central nervous system involvement in an allogeneic hematopoietic stem cell transplant recipient.

Trichosporon is an ubiquitous yeast that has emerged as an opportunistic pathogen in the immunocompromised host. We describe a case of invasive trichosporonosis in an allogeneic hematopoietic stem cell transplant (allo-HSCT) recipient while on caspofungin antifungal prophylaxis. She developed disseminated trichosporonosis in the pre-engraftment period and was successfully treated with voriconazole. She later developed 2 further episodes of invasive trichosporonosis involving the central nervous system. This case highlights the challenges of managing trichosporonosis in allo-HSCT recipients and suggests the need for lifelong therapy in some patients.

Impact of COVID-19 on TB epidemiology in South Korea.

SETTING: Five referral hospitals, South Korea.OBJECTIVE: To assess epidemiological changes in TB before and during the COVID-19 pandemic.DESIGN: This was a multicentre cohort study of 3,969 patients diagnosed with TB.RESULTS: We analysed 3,453 patients diagnosed with TB prior to the COVID-19 pandemic (January 2016-February 2020) and 516 during the pandemic (March-November 2020). During the pandemic, the number of patients visits declined by 15% from the previous 4-year average, and the number of patients diagnosed with TB decreased by 17%. Patients diagnosed during the pandemic were older than those diagnosed before the pandemic (mean age, 60.2 vs. 56.6 years, P < 0.001). The proportion of patients to have primary TB at a younger age (births after 1980) among those diagnosed with TB was significantly lower during the pandemic than before (17.8% in 2020 vs. 23.5% in 2016, 24.0% in 2017, 22.5% in 2018, 23.5% in 2019; P = 0.005).CONCLUSIONS: The COVID-19 pandemic resulted in a reduction in the number of visits to respiratory departments, leading to fewer patients being diagnosed with TB. However, our results suggest that universal personal preventive measures help to suppress TB transmission in regions with intermediate TB burden.

VDUP1 potentiates Ras-mediated angiogenesis via ROS production in endothelial cells.

Vitamin D3 up-regulated protein 1 (VDUP1) is a tumor suppressor of which expression is reduced in a variety of cancer cells, and enforced expression inhibits the tumor cell proliferation. It inhibits the activity of thioredoxin, thus contributing cellular ROS generation. Since ROS is a critical factor for angiogenesis, we investigated the role of VDUP1 in angiogenesis and endothelial proliferation. The expression of VDUP1 was upregulated by overexpression of an oncogene, Ras. Enforced expression of VDUP1 increases ROS production and proliferation of Ras-overexpressing endothelial cells. Overexpression of VDUP1 increases the resistance to the anchorage-dependent cell death and tube formation of the Ras-overexpressing endothelial cell. In addition, the removal of ROS by ROS scavenger attenuates the effect of VDUP1 on tube formation. These results suggest that VDUP1 is involved in Ras-mediated angiogenesis via ROS generation in endothelial cells.

Decreased urinary secretion of belotecan in folic acid-induced acute renal failure rats due to down-regulation of Oat1 and Bcrp.

The effects of folic acid-induced acute renal failure on the renal excretion of belotecan were investigated in rats after intravenous administration. Both glomeruli and renal tubules were seriously damaged by folic acid-induced acute renal failure. The renal excretion clearance, CLr, of belotecan was significantly decreased by folic acid-induced acute renal failure. Furthermore, glomerular filtration rate and secretion clearance of the drug were dramatically decreased by folic acid-induced acute renal failure. In vivo renal uptake of belotecan was inhibited by p-aminohippurate, whereas renal excretion was inhibited by GF120918, but not by verapamil and bromosulphalein. This indicates that Oat1/3 and Bcrp are involved in the renal uptake and urinary excretion of belotecan, respectively. Both mRNA and protein levels of Oat1, Oat3 and Bcrp were significantly decreased in folic acid-induced acute renal failure rats. Based on the finding that belotecan is a substrate of OAT1 but not of OAT3, the decrease in CLr of belotecan in folic acid-induced acute renal failure could, therefore, mainly be attributed to the down-regulation of Oat1 and Bcrp, in addition to the decrease in glomerular filtration rate.

Tissue-specific changes in mRNA expression of Abc and Slc transporters in murine pulmonary tuberculosis.

A pulmonary tuberculosis mouse model was used to assess the pharmacodynamic and pharmacokinetic characteristics of tuberculosis therapeutics. While membrane transporters play important roles in drug disposition and physiological homeostasis, their expressional changes and contribution have never been analysed in a tuberculosis animal model. The mRNA expression level of 20 Abc family transporters and 32 Slc family transporters in tuberculosis-infected mice were compared with those in naïve uninfected mice using real-time polymerase chain reaction (PCR). Mycobacterium tuberculosis infection induced many dramatic expression changes of families of both Abc transporters and Slc transporters at 4 and 8 weeks, as observed in the livers, kidneys, and intestines of test mice--and in a different mode, in the lungs and spleens as well. These changes were dependent on the tuberculosis progression with the tissue-specific manner, that is, in the lungs, the number of transporters of which the expression level changed due to M. tuberculosis infection had increased, and the magnitude of change also greater at 8 weeks, while in the spleen, the transcription of most transporters except Mrps had not changed or had recovered back to the same level of naïve transcription at 8 weeks. Understanding the expression changes of transporters will assist in setting up rational preclinical dosing plans through the ability to predict the pharmacokinetics of new anti-tuberculosis chemotherapeutics and, furthermore, will assist in the design of safer and more efficient drug regimens.

Metabolic syndrome and visceral obesity as risk factors for reflux oesophagitis: a cross-sectional case-control study of 7078 Koreans undergoing health check-ups.

BACKGROUND: Obesity has been associated with reflux oesophagitis. However, the relationship between metabolic syndrome characterised by visceral obesity and reflux oesophagitis is unclear. AIM: To investigate whether metabolic syndrome or visceral obesity is a risk factor for reflux oesophagitis. METHODS: A cross-sectional study of 7078 subjects undergoing upper endoscopy during health check-ups was conducted (3539 patients with reflux oesophagitis vs age- and sex-matched controls). We further analysed according to categories of visceral adipose tissue and subcutaneous adipose tissue area with 750 cases and age-, sex- and waist circumference-matched controls who underwent abdominal CT scan. RESULTS: The prevalence of metabolic syndrome was higher in cases than controls (26.9% vs 18.5%, p<0.001). Multivariate analysis demonstrated that metabolic syndrome is associated with reflux oesophagitis (odds ratio (OR) = 1.42; 95% confidence interval (CI), 1.26 to 1.60). Among the individual components of metabolic syndrome, waist circumference (OR = 1.47; 95% CI, 1.30 to 1.65) and triglyceride (OR = 1.20; 95% CI, 1.05 to 1.36) independently increased the risk for reflux oesophagitis. On sub-analysis, cases showed higher mean visceral adipose tissue area (cm(2)) (136.1 (SD 57.8) vs 124.0 (SD 54.7), p<0.001) and subcutaneous adipose tissue area (cm(2)) (145.9 (SD 56.8) vs 133.5 (SD 50.7), p<0.001). However, only visceral adipose tissue area was an independent risk factor for reflux oesophagitis after adjusting for multiple confounders including smoking, alcohol, body mass index (BMI) and subcutaneous adipose tissue area (OR = 1.60; 95% CI, 1.03 to 2.48, lowest quartile vs highest quartile). CONCLUSIONS: Metabolic syndrome was associated with reflux oesophagitis. Abdominal obesity, especially visceral obesity, was an important risk factor for reflux oesophagitis.

Pharmacokinetic interaction between DA-8159, a new erectogenic, and metformin in rats: competitive inhibition of metabolism via hepatic CYP3A1/2.

BACKGROUND AND PURPOSE: Erectile dysfunction is highly prevalent in diabetic patients and PDE V inhibitors are effective and safe for the treatment of erectile dysfunction in men with diabetes. Therefore, in this study we investigated whether a pharmacokinetic interaction occurs between DA-8159 and metformin, as both drugs are metabolized via hepatic CYP3A1/2 in rats. EXPERIMENTAL APPROACH: DA-8159 (30 mg kg(-1)) and metformin (100 mg kg(-1)), both separately and together, were administered to rats either intravenously or orally. The V (max), K (m), CL(int), apparent inhibition constants (K (i)), [I]/K (i) and concentrations of each drug in the liver and intestine were then measured. KEY RESULTS: After i.v. administration of both drugs simultaneously, the AUC of DA-8159 and metformin was significantly greater (21.2 and 33.9% increase for DA-8159 and metformin, respectively) than that of each drug alone. After p.o. administration of the drugs, the AUC of metformin was also significantly greater (20.7% increase) in the presence of DA-8159 than in its absence. However, the AUC of DA-8159 was similar in the absence and presence of metformin. CONCLUSIONS AND IMPLICATIONS: The significantly greater AUC of metformin and DA-8159 after i.v. administration of both drugs and of metformin after p.o. administration of both drugs is probably due to competitive inhibition for the metabolism of these drugs via hepatic CYP3A1/2. However, the similar AUCs of DA-8159 in the absence and presence of metformin, after p.o. administration, indicates that the dose of metformin used was insufficient to inhibit the hepatic and intestinal metabolism of DA-8159.

Diagnostic value of brain MRI and 18F-FDG PET in the differentiation of Parkinsonian-type multiple system atrophy from Parkinson's disease.

BACKGROUND AND PURPOSE: Differentiation between parkinsonian type multiple system atrophy (MSA-P) and Parkinson's disease (PD) is important but often difficult. We investigated the diagnostic value of brain magnetic resonance imaging (MRI) and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in differentiating MSA-P from PD. METHODS: Twenty-four patients with MSA-P (16 probable and 8 possible) and eight patients with PD were included in this study. RESULTS: For analysis using the putaminal findings, the sensitivities were 58.3% by visual analysis of brain MRI, 95.8% by visual analysis of (18)F-FDG PET, and 79.2% by statistical parametric mapping (SPM) analysis of (18)F-FDG PET in differentiating MSA-P from PD; the specificity was 100% for each analysis. Using the putaminal findings, visual analysis of (18)F-FDG PET had a higher sensitivity compared with brain MRI (P = 0.004) and SPM analysis of (18)F-FDG PET revealed a tendency towards higher sensitivity compared with brain MRI (P = 0.063). For analysis using both putaminal and infratentorial findings, the sensitivities were 79.2% by visual analysis of brain MRI, 95.8% by visual analysis of (18)F-FDG PET, 95.8% by SPM analysis of (18)F-FDG PET in differentiating MSA-P from PD; the specificity was 100% for each analysis. CONCLUSION: Both brain MRI and (18)F-FDG PET showed diagnostic usefulness in differentiating MSA-P from PD, with (18)F-FDG PET being more sensitive than brain MRI.