IgG4-Related Hepatic Inflammatory Pseudotumor Complicated by Actinomycosis during Steroid Therapy

For a 67-year-old man with diabetes mellitus, a 9-cm liver mass was found on CT during the diagnostic work-up for weight loss and fever. Dynamic CT and MRI showed a layered pattern of contrast enhancement suggesting the imaging features of the solid inflammatory mass. After tissue diagnosis of immunoglobulin G4 (IgG4)-related disease by gun needle biopsy, steroid therapy induced partial shrinkage of the mass on the follow-up CT at 4 weeks. On the 5-month follow-up CT with the maintenance of low-dose oral steroid medication, disease progression with invasion to diaphragm brought surgical intervention of right hemihepatectomy considering the possibility of combined malignancy. In the area of diaphragmatic destruction, focal actinomycosis was complicated in the main mass of IgG4-related disease. We are the first to describe a rare case of IgG4-related inflammatory pseudotumor, complicated by actinomycosis, showing an invasive nature that mimicked malignancy during steroid therapy in a diabetic patient.

Extrapyramidal Signs and Risk of Progression from Mild Cognitive Impairment to Dementia: A Clinical Research Center for Dementia of South Korea Study

OBJECTIVE: Extrapyramidal signs (EPS) are common in patients with mild cognitive impairment (MCI). However, few studies have assessed the effect of EPS on the clinical course of MCI. We aimed to evaluate whether patients with EPS show more frequent progression from MCI to Alzheimer's disease (AD) and to other types of dementia. METHODS: Participants (n=882) with MCI were recruited, and were followed for up to 5 years. The EPS positive group was defined by the presence of at least one EPS based on a focused neurologic examination at baseline. RESULTS: A total of 234 converted to dementia during the follow-up period. The risk of progression to AD was lower in the patients with EPS after adjusting for potential confounders [hazard ratio (HR)=0.70, 95% confidence interval (CI)=0.53–0.93, p=0.01]. In contrast, the patients with EPS had a six-fold elevated risk of progression to dementia other than AD (HR=6.33, 95%CI=2.30–17.39, p < 0.001). CONCLUSION: EPS in patients with MCI is a strong risk factor for progression of MCI to non-Alzheimer dementia. The careful neurologic examination for EPS in patients with MCI can yield important clinical information for prognosis.

Association between the BDNF Val66Met Polymorphism and Chronicity of Depression

OBJECTIVE: Both clinical and biological factors influence the course of depressive disorders. This study tested for associations between the brain-derived neurotrophic factor (BDNF) gene at the Val66Met locus and the course of major depressive disorder (MDD). METHODS: Three hundred ten Korean subjects (209 patients, 101 controls) were genotyped for rs6265 at nucleotide 196 (G/A), which produces an amino acid substitution at codon 66 (Val66Met) of the gene for BDNF. Course of illness was evaluated both by chronicity of current episode (episode duration >24 months) and by the lifetime history of recurrences. RESULTS: Patients with the Met/Met BDNF genotype had a significantly higher rate of chronic depression than all others. There was a significant dose effect of the Met allele on chronicity. Compared with the Val/Val genotype, the relative risk of chronicity was 1.67 for the Val/Met genotype, and 2.58 for the Met/Met genotype. Lifetime history of recurrent episodes was not related to BDNF genotypes but was significantly associated with younger age of onset and with a history of depression in first degree relatives. CONCLUSION: BDNF genotyping may be informative for anticipating chronicity in major depression.

An Association Study between Various Adrenergic Alpha 2 Receptor Polymorphisms and Treatment Response to Mirtazapine in Major Depression

OBJECTIVES: Genetic differences may contribute to the inter-individual differences in treatment response to antidepressants among patients suffering from major depression. This study investigated a possible association of treatment response to mirtazapine with various adrenergic alpha 2 receptor polymorphisms in major depressive patients. METHODS: A 6-week naturalistic treatment study with a blinded outcome examined 84 Korean patients with major depression. Treatment response to mirtazapine was defined as > or =50% decrease in HAM-D scores at six weeks. In this study, four genetic polymorphisms were selected ; ADRA2A MspI, ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325. RESULTS: The Del/Del genotype of alpha2CDel322-325 exhibited a significant association with response to mirtazapine through multiple logistic regression. ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325 did not showed a significant association with response to mirtazapine. CONCLUSION: Based on the finding that alpha2CDel322-325 polymorphism had an association with the mirtazapine response, we postulate that the polymorphism related to the mechanism of the antidepressant effect is important in predicting the response to antidepressants.

An Association Study between Various Adrenergic Alpha 2 Receptor Polymorphisms and Treatment Response to Mirtazapine in Major Depression

OBJECTIVES: Genetic differences may contribute to the inter-individual differences in treatment response to antidepressants among patients suffering from major depression. This study investigated a possible association of treatment response to mirtazapine with various adrenergic alpha 2 receptor polymorphisms in major depressive patients. METHODS: A 6-week naturalistic treatment study with a blinded outcome examined 84 Korean patients with major depression. Treatment response to mirtazapine was defined as > or =50% decrease in HAM-D scores at six weeks. In this study, four genetic polymorphisms were selected ; ADRA2A MspI, ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325. RESULTS: The Del/Del genotype of alpha2CDel322-325 exhibited a significant association with response to mirtazapine through multiple logistic regression. ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325 did not showed a significant association with response to mirtazapine. CONCLUSION: Based on the finding that alpha2CDel322-325 polymorphism had an association with the mirtazapine response, we postulate that the polymorphism related to the mechanism of the antidepressant effect is important in predicting the response to antidepressants.

Comparative Assessment of Clinical Efficacy after 12-Month Clinical Trial of Donepezil between the Patients with Pure Alzheimer's Disease and Mixed Dementia

OBJECTIVES: The purpose of this study was to compare the efficacy of donepezil treatment between patients with pure Alzheimer's disease (AD) and Mixed dementia (MD) during a 12-month trial. METHODS: A total of 139 patients were recruited for this 52-week study. The effect of donepezil on cognitive function was measured using Alzheimer's Disease Assessment Scale-cognitive subscale-preliminary Korean version (ADAS-cog-K). Patients' activities of daily living using the Seoul-Instrumental Activities of Daily Living (S-IADL) and Seoul-Activities of Daily Living (S-ADL);behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline, 13-weeks, 26-weeks, 39-weeks and 52-weeks. We defined the responsive patients to donepezil at those who showed a cognitive improvement or no change during the first six-month clinical trial. RESULTS: 84 pure AD patients and 34 MD patients were available for intent-to-treat (ITT) last observation carried forward (LOCF) analysis. There was no significant difference between two groups in mean change from baseline in the total ADAS-cog-k, S-ADL, S-IADL and K-NPI scores at 52-week. Based on the operational criteria, 60.7% of pure AD patients and 58.8% of MD patients were responders to donepezil. CONCLUSION: MD patients had similar levels of efficacy with pure AD patients and donepezil was well tolerated in both groups. These results suggest that donepezil is an effective and well-tolerated treatment for MD patients as well as for pure AD patients.

Comparative Assessment of Clinical Efficacy after 12-Month Clinical Trial of Donepezil between the Patients with Pure Alzheimer's Disease and Mixed Dementia

OBJECTIVES: The purpose of this study was to compare the efficacy of donepezil treatment between patients with pure Alzheimer's disease (AD) and Mixed dementia (MD) during a 12-month trial. METHODS: A total of 139 patients were recruited for this 52-week study. The effect of donepezil on cognitive function was measured using Alzheimer's Disease Assessment Scale-cognitive subscale-preliminary Korean version (ADAS-cog-K). Patients' activities of daily living using the Seoul-Instrumental Activities of Daily Living (S-IADL) and Seoul-Activities of Daily Living (S-ADL);behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline, 13-weeks, 26-weeks, 39-weeks and 52-weeks. We defined the responsive patients to donepezil at those who showed a cognitive improvement or no change during the first six-month clinical trial. RESULTS: 84 pure AD patients and 34 MD patients were available for intent-to-treat (ITT) last observation carried forward (LOCF) analysis. There was no significant difference between two groups in mean change from baseline in the total ADAS-cog-k, S-ADL, S-IADL and K-NPI scores at 52-week. Based on the operational criteria, 60.7% of pure AD patients and 58.8% of MD patients were responders to donepezil. CONCLUSION: MD patients had similar levels of efficacy with pure AD patients and donepezil was well tolerated in both groups. These results suggest that donepezil is an effective and well-tolerated treatment for MD patients as well as for pure AD patients.

Comparative Assessment of Clinical Efficacy between the Naive and the Switching Group to Donepezil: 12 Months Prospective Study

OBJECTIVES: The purpose of this study was to compare the efficacy between switching patients with Alzheimer's disease (AD) from galantamine or rivastigmine to donepezil because they were not responding adequately, and naive patients with AD who initiated therapy with donepezil. METHODS: A total of 108 patients were recruited for this 52-week study. The effect of donepezil on cognitive function was measured using Alzheimer's Disease Assessment Scale-cognitive subscale-preliminary Korean version (ADAS-cog-K). Patients' activities of daily living using Seoul-Activities of Daily Living (S-ADL) and the Seoul-Instrumental Activities of Daily Living (S-IADL);behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline, 13-weeks, 26-weeks, 39-weeks and 52-weeks. We defined the responsive patients to donepezil at those who showed a cognitive improvement or no change during the first six-month clinical trial. RESULTS: 86 naive patients and 22 switching patients were enrolled in the study. 74 patients completed the study and 34 discontinued their treatment before week 52. There was no significant difference between two patient groups in demographic data, baseline characteristics and dementia severity except duration of illness. The total ADAS-cog-K scores were not significantly different from baseline after 52 weeks of treatment in both groups. Both groups demonstrated deterioration of S-ADL and S-IADL at 52 weeks. The NPI scores did not significantly change in both groups. Based on the operational criteria, 61.6% of the naive group and 54.5% of the switching group were responders to donepezil. CONCLUSION: The switching group had similar levels of efficacy with the naive group who initiated therapy with donepezil. These results suggest that patients not responding adequately to rivastigmine or galantamine may improve or stabilize after switching to donepezil and prior medication does not effect donepezil's efficacy.

Comparative Study of Serum Brain-Derived Neurotrophic Factor in Acute and Chronic Depression / 대한정신약물학회지

OBJECTIVE: The aim of this study was to compare the serum brain-derived neurotrophic factor (BDNF) in acute depression with that in chronic depression. METHODS: Eighty subjects who met criteria for major depressive disorder (MDD) were recruited. Patients experiencing at least their fourth episode or an episode of at least 24 months in duration were defined as chronically depressed (n=21). Other patients were classified as acutely depressed (n=59). Antidepressant medications were administered for 6 weeks. Serum BDNF and Hamilton rating scale for depression (HAM-D) scores were measure before and after the administration of medication. RESULTS: We found significant differences in serum BDNF between the two groups. Serum BDNF was significantly higher among those with chronic depression than among those with acute depression both at baseline and after medication. CONCLUSION: This study suggested that serum BDNF might constitute a potential biological marker for chronic depression.

Impairment of Instrumental Activities of Daily Living in Patients with Mild Cognitive Impairment

OBJECTIVE: This study was conducted to examine the following: whether patients with mild cognitive impairment (MCI) show impairments in instrumental activities of daily living (IADL) as compared to controls; to identify the functional sub-domains of instrumental activities of daily living (IADL) that are affected in MCI and, finally, to identify the Seoul-Instrumental Activities of Daily Living (S-IADL) scale cut-off score that best differentiated between MCI and controls. METHODS: This study was carried out at the geropsychiatry clinic, university hospital. The study participants included 66 patients with MCI and 61 normal elderly. The S-IADL and Seoul-Activities of Daily Living (S-ADL) scales were administered to the main caregivers of all participants in order to assess everyday functioning. RESULTS: The total S-IADL score was significantly higher in the patients with MCI [mean (SD) score=4.47 (2.06)] than in the controls [mean (SD) score=1.44 (1.65)] (p<0.001). The patients with MCI performed significantly worse on IADLs, such as the ability to use the telephone, prepare meals, take medication, manage belongings, keep appointments, talk about recent events, and perform leisure activities/hobbies (p<0.05). The S-IADL scale discriminated well between patients with MCI and controls (Area Under Curve=87%). CONCLUSION: The patients with MCI showed impairments in the ability to perform complex ADL in comparison to healthy controls. IADLs related to memory and frontal/executive functioning were particularly affected in MCI.

An Association Study between Various Monoamine Transporter Gene Polymorphisms and Treatment Response to Mirtazapine in Major Depression / 대한정신약물학회지

OBJECTIVE: Genetic differences may contribute to the inter-individual differences in treatment response to antidepressants among patients suffering from major depression. This study investigated a possible association of various monoamine transporter genetic polymorphisms with treatment response to mirtazapine in major depressive patients in elderly. METHODS: In this study, three genetic polymorphisms were selected: serotonin transporter 5- HTTLPR, serotonin transporter 5-HTT intron 2 VNTR, and norepinephrine transporter NET (G1287A). The patients with major depression diagnosed by DSM-IV were recruited to a 6 week naturalistic mirtazapine treatment study in Samsung Medical Center. Treatment response to mirtazapine was defined as > or =50% decrease in HAMD-17 scores at 6 weeks, and the genotypes in the patients were determined using the polymerase chain reaction. RESULTS: Our results showed that ss allele carriers were included more in responder group (ss allele in responder vs. non responder group; 69.4% vs. 40.0%). In addition, l-allele (sl/ll) carriers were included less in responder group (sl/ll allele in responder vs. non responder group; 30.6% vs. 60.0%). Multiple logistic regression analyses showed the 5-HTTLPR polymorphism as an predictor of the mirtazapine response (5HTTLPR ss allele carrier vs. l-allele (sl/ll) carrier; odds ratio: 3.81; 95% confidence interval [CI], 1.32-11.0; p=0.013). However, 5-HTT intron 2 VNTR l/s (p=0.33 by multiple logistic regression; [OR], 0.53; 95% [CI], 0.15-1.88), and NET (G1287A) G/A (p=0.68 by multiple logistic regression; [OR], 1.25; 95% [CI], 0.44-3.53) showed no statistical significant influences on response rate. CONCLUSION: In conclusion, 5HTTLPR polymorphism may predict treatment response to mirtazapine in major depressive patients in elderly.

A Fetus with Persistent Hyperextended Neck Complicated with Ventriculomegaly and Pulmonary Immaturity in Third Trimester / 대한주산의학회잡지

Hyperextended neck of the fetal head is among the various fetal attitudes detected by prenatal sonography. Various etiologies may lead to hyperextension of the fetal head, including fetal anomalies such as structural abnormalities, conjoined twins and fetal neck masses, nuchal cord and uterine factors such as leiomyoma and uterine malformations. The importance of the precise prenatal diagnosis of this condition relates not only to the delivery mode, but also to the detection of associated conditions, as noted above. We report a case of a fetus whose persistent hyperextended neck was detected by midtrimester sonography, and who later demonstrated ventriculomegaly and lung immaturity in the 3rd trimester.

A Case of Congenital Cytomegalovirus Infection with Severe Hydrocephalus in Prenatal Ultrasonography / 대한산부인과학회잡지

Cytomegalovirus (CMV) infection is one of the most common viral infections in human and it is known to cause primary and recurrent infections. CMV is spread to the fetus in 40% of pregnancies in primary infection, while 0.5-1% of pregnancies in recurrent infection are known to cause congenital infections. Only 10% of such infections are presented with severe symptoms, with the other 90% being asymptomatic. However, there are no definite methods to predict the manifestation of fetal infections or specific treatments in such cases. Intraventricular calcification, ventriculomegaly, intraventricular adhesion, abnormal patterns of brain fissures, brain atrophy, abnormal findings of cerebellum and cisterna magna, and hyperechoic bowels can be presented by ultrasonography in CMV infection. We introduce a case of CMV infection presented as ventriculomegaly and hyperechoic bowels by ultrasonography and pathologically confirmed by autopsy.

Prevalence of aspirin sensitivity among asthmatic patients with mild to moderate severity and its clinical characteristics / 천식및알레르기

BACKGROUND: While aspirin sensitivity has been known to be common among patients with severe asthma, its frequency among asthmatics with mild to moderate severity remains to be learned. OBJECTIVES: To elucidate the frequency of aspirin sensitivity and its clinical characteristics among asthma patients with mild to moderate severity. MATERIAL AND METHODS: A total of 96 asthmatics with mild to moderate severity were enrolled. They underwent lysine-aspirin and methacholine bronchial provocation tests, and gave their induced sputum after the lysine-aspirin challenge. RESULTS: FEV1 declined greater than 20% compared with baseline FEV1 in 11 of 96 patients on the lysine-aspirin challenge. The frequency of aspirin sensitivity was higher among patients with enhanced bronchial hyperresponsiveness to methacholine (PC20 < 1 mg/ml) than among those without it (27.3% vs. 6.8%). The frequency was also higher in those with induced sputum eosinophil count higher than 3% than among those without it (38.9% vs. 0%). However, it was not associated with other risk factors such as age, sex, atopy, nasal polyps, and rhinosinusitis. CONCLUSION: More than 10% of mild to moderate asthmatics have aspirin sensitivity even though they have experienced no history of aspirin sensitivity which may be related with bronchial hyperresponsiveness to methacholine and eosinophil activation.

A Prospective Study of Asthma Prevalence and Atopy Rate in Children Living in Rural Area of Cheju Island for 3 Years / 소아알레르기및호흡기학회지

PURPOSE: Asthma has been increasing due to changes in life style and indoor environments. Manifestations of asthma and atopy varies according to age. The purpose of this study was to elucidate the changing prevalence of asthma and atopy in children living in rural area of Cheju island via three year prospective study. METHODS: A total of 314 subjects aged from 7 to 12 years was followed up for three years. They responded a ISAAC questionnare, underwent allergy skin prick test with common aeroallergens and methacholine bronchial provocation test. Children with asthma symptoms on a questionnaire and positive methacholine bronchial provocation test were diagnosed as bronchial asthma. Skin prick test was regarded as positive when the size of wheal caused by allergens was same or larger than that caused by histamine. RESULTS: The prevalence of bronchial asthma has a tendency to increase from 4.1 % to 7.3% three years later(P=0.08). The atopy rate has significantly increased from 34.1% to 49.2% in both girls and boys(P<0.001), from 35.0% to 46.9% in girls(P< 0.05), and from 33.3% to 51.3% in boys(P<0.05). The positive skin responses to Dermatophagoides pteronyssinus, D. farinae(P=0.36), Japanese cedar and cockroach were not changed between the three years. However, the postive skin reponse to citrus red mite was significantly increased three years later(from 10.7% to 31.1%, P<0.001). CONCLUSION: The asthma prevalence has a tendency to increase in children living in rural area with citrus farms. The atopy rate has been also increasing in the rural children. These phenomena may be explained by the fact that sensitization to citrus red mite has been increasing when they are getting older.

Relationship of eosinophils in induced sputum with bronchial responsiveness to methacholine or capsaicin and with responses to anti-asthmatic treatment in chronic cough patients / 천식및알레르기

BACKGROUND: The value of the induced sputum examination in chronic cough has not been determined. We performed this study to investigate the relationship between eosinophil percentage on induced sputum and bronchial responsiveness to methacholine or capsaicin, and responses to anti-asthmatic treatment in chronic cough patients. SUBJECTS AND METHODS: Forty-seven patients with chronic cough persisting for more than 1 month without current wheezing or dyspnea were studied. According to the eosinophil percentage on induced sputum, the subjects were divided into two groups: group A (sputum eosinophil > or = 3%) and group B (sputum eosinophil < 3%). Methacholine bronchial provocation test (MBPT) and capsaicin challenge, and responses to anti-asthmatic treatment were compared between the two groups. RESULTS: Group A consisted of 26 subjects and group B consisted of 21 subjects. There were no differences in sex, clinical characteristics of cough, atopy prevalence, and peripheral eosinophil counts except serum IgE level between the two groups. MBPT positivity was much higher in group A than group B (46.2% vs 0%, p<0.001), but there was no difference in capsaicin test positivity (44.0% vs 50.0%). Group A showed much higher response rates to anti-asthmatic treatments than in group B (73.1% vs 19.0%, p<0.001). CONCLUSION: Eosinophilic airway inflammation in chronic cough was related to methacholine bronchial hyperresponsiveness, but not to capsaicin cough threshold. Induced sputum eosinophil percentage was a good indicator in predicting the response to anti-asthmatic treatment in most chronic cough patients.

Comparison of basophil histamine releasability between atopic and nonatopic thmatics

To compare the mediator releasability between atopic and nonatopic asthmatics, we measured basophil histamine releasability (BaHR) using a calcium-ionophore A23187 and anti-IgE in 137 subjects who were treated at Seoul National University Hospital. Subjects were categorized into atopic (group AA, n=77) or nonatopic asthmatics (group NA, n=32), or normal controls (group NC, n=28). Serum total IgE levels were determined and correlation with BaHR was assessed. Anti-IgE-induced maximal BaHR in groups AA, NA, and NC was 41.0+/-3.2, 23.1+/-4.5, and 16.8+/-3.8, respectively (mean+/-SE, %). Anti-IgE-induced BaHR in group AA was significantly higher than that in groups NA and NC (p<0.05). Calcium ionophore A23187-induced maximal BaHR was 43.1+/-2.8, 40.8+/-4.4, and 50.5+/-5.2, respectively (mean+/-SE, %), and there was no significant difference among the groups. Serum total IgE level correlated significantly with anti-IgE-induced maximal BaHR (r=0.281, p<0.01) but not with that induced by calcium ionophore A23187. In conclusion, IgE receptor-related BaHR is higher in atopic asthmatics than in nonatopic asthmatics, and this increased BaHR in atopics is significantly associated with increased serum total IgE level.

Association of HLA-DRB1 genotype with sensitivity to house dust mite / 천식및알레르기

BACKGROUND: It is known that HLA molecule can restrict specific IgE responses, but few studies have documented the association between HLA and sensitization to house dust mite(HDM). OBJECTIVE: To evaluate whether a specific HLA type can be a risk or protective factor for the development of HDM sensitivity. METHOD: Total 146 subjects were genotyped for HLA-DRB1 using PCR-SSP technique and HDM sensitivity, determined by skin prick test using two mite allergens, D. pteronyssinus (Dp) and D. farinae (Df). Subjects were grouped according to Dp or Df sensitivity and linkage analysis between HDM sensitivity and HLA-DRB1 genotype was performed. RESULTS: The data revealed higher allele frequencies of DRB1*07 in Dp or Df sensitive groups compared to insensitive groups (11.6% vs. 2.6% in Dp, 11.5% vs. 3.3% in Df group, p<0.05), but the other allele frequencies showed no difference. CONCLUSION: There was a significant association between HLA-DRB1*07 genotype and HDM sensitization. These results indicate that antigen presentation by HLA class II molecule restricts the development of specific IgE response to HDM.