A Pilot Study for Discovering Candidate Genes of Chromosome 18q21 in Methamphetamine Abusers: Case-control Association Study.

OBJECTIVE: It was previously suggested that the malic enzyme 2 (ME2) as the candidate gene for psychosis in fine mapping of chromosome 18q21. Chromosome 18q21 is also one of the possible regions that can contribute to addiction. METHODS: We performed a pilot study for discovering candidate gene of chromosome 18q21 in the methamphetamine abusers for elucidating the candidate gene for methamphetamine addiction leading to psychosis. We have selected 30 unrelated controls (16 males, 14 females; age=59.8±10.4) and 37 male methamphetamine abusers (age=43.3±7.8). We analyzed 20 single nucleotide polymorphisms (SNPs) of 7 neuronal genes in chromosome 18q21 for DNA samples that was checked for the data quality and genotype error. The association between the case-control status and each individual SNP was measured using multiple logistic regression models (adjusting for age and sex as covariates). And we controlled false discovery rate (FDR) to deal with multiple testing problem. RESULTS: We found 3 significant SNPs of 2 genes in chromosome 18q21 (p-value<0.05; adjusting for age as covariate) in methamphetamine abusers compared to controls. We also found 2 significant SNPs of 1 gene (p-value<0.05; adjusting for age and sex as covariates) (rs3794899, rs3794901:MAPK4). Two SNPs in MAPK4 gene were significant in both statistical groups. CONCLUSION: MAPK4, the gene for mitogen-activated protein kinase 4, is one of the final 6 candidate genes including ME2 in 18q12-21 in our previous finemapping for psychosis. Our results suggest that MAPK4 can be a candidate gene that contribute to the methamphetamine addiction leading to psychosis.

Amnestic multiple cognitive domains impairment and periventricular white matter hyperintensities are independently predictive factors progression to dementia in mild cognitive impairment.

OBJECTIVE: Mild cognitive impairment (MCI) usually represents a transitional phase between normal cognitive function and dementia, but not all people with MCI develop dementia because MCI is a clinically and etiologically heterogeneous grouping. The aim of this study was to determine whether clinical subtypes of MCI and severity of white matter hyperintensities (WMH) were associated with progression of MCI to dementia. METHOD: Our study cohort consisted of 840 patients aged 55 years or older who had a diagnosis of MCI at their baseline visit and had at least one follow-up contact after baseline. RESULTS: The results of the multivariable Cox proportional hazards model analysis revealed that both multiple domain amnestic MCI with WMH and multiple domain amnestic MCI without WMH were a significantly more likely to progress to dementia in comparison with patients with non-amnestic MCI. Logistic regression analyses showed that PWMH (periventricular white matter hyperintensities), not the deep white matter hyperintensities, was significantly associated with incident dementia. CONCLUSIONS: This study showed that mdMCI + a (-NL or -WMH) are more associated with progression to dementia. We also found that increasing severity of PWMH, not deep white matter hyperintensities, was significantly associated with incident dementia, independently of subtype of MCI. It suggests that both mdMCI + a and PWMH are good prognostic factors of progression to dementia in MCI.

Prognostic factor analysis in patients with metastatic spine disease depending on surgery and conservative treatment: review of 577 cases.

BACKGROUND: To date, skillful medical management and advanced surgical techniques have provided increased quality of life with less postoperative morbidity in patients with spinal metastasis. We assessed the survival of patients with spinal metastasis according to two treatment modalities: surgery and conservative treatment. METHODS: From 2005 to 2010, a total of 577 patients (200 surgery, 377 conservative treatment) who had spinal metastasis were enrolled. Prognostic factors and survival were assessed by Cox regression and Kaplan-Meier analyses in patients receiving either surgery or conservative treatment. RESULTS: The mean age was 59.7 (range 21-87) years in the surgery group and 59.9 (range 28-90) years in the conservative treatment group. The major primary cancers were of lung, liver, and colorectal origin in the surgery group and lung, liver, and breast in the conservative group. The mean±SD Tokuhashi score in the surgery group was 8.12±3.09 and in the conservative group was 8.0±2.8 (not significant). The hazard ratio of the primary cancer group ranged from 1.870 to 3.217 compared to that of the most favorable primary cancer group in all patients. Survival was affected significantly by sex, adjuvant therapy, and postoperative survival in the surgery group and by clinical symptom, metastasis to major internal organ, and primary cancer origin in the conservative group. CONCLUSIONS: With this retrospective review of 577 cases of spinal metastasis, different prognostic factors depending on the treatment modality were discovered. Hence, consideration of these factors depending on the treatment modality could be helpful in treating patients with spinal metastasis.

Association of the Neuronal Cell Adhesion Molecule (NrCAM) Gene Variants with Personality Traits and Addictive Symptoms in Methamphetamine Use Disorder.

OBJECTIVE: 1) To investigate the relationship between NrCAM polymorphisms and methamphetamine abuse in an ethnically homogenous Korean population. 2) To further support our findings by investigating the association among NrCAM gene variants, certain personality traits, and addictive symptoms of methamphetamine abusers. METHODS: Thirty-seven male methamphetamine abusers (age=43.3±7.8) and30 non-users (16 men, 14 women; age=59.8±10.4) were recruited. Ten single nucleotide polymorphisms (SNPs) in the NrCAM gene were assayed to compare genotype distributions between the 2 groups. Personality characteristics were measured using the Temperament and Character Inventory (TCI) and the NEO Personality Inventory, Revised (NEO PI-R). Addictive symptoms were assessed using the Diagnostic Interview for Genetic Studies (DIGS) and reviews of the subject's medical records. RESULTS: Among the 10 SNPs in the NrCAM gene, the frequency of the TA genotype at rs1990162 was significantly lower in methamphetamine abusers compared to non-users (p=0.042). In the 3 NrCAM gene SNPs (rs381318, rs2072546, and rs6954366), the distribution of genotypes and alleles were significantly associated with some traits in the TCI and NEO PI-R. Genotypes and alleles at 5 gene SNPs (rs2142325, rs381318, rs1269621, rs1269634, and rs1990162) were associated with certain addictive symptom dimensions in the patients. CONCLUSION: These findings support the idea that NrCAM is associated with genetic susceptibility of methamphetamine abuse and is also associated with certain personality characteristics that may increase disturbed addictive behavior.

Transpedicular curettage and drainage of infective lumbar spondylodiscitis: technique and clinical results.

BACKGROUND: Infective spondylodiscitis usually occurs in patients of older age, immunocompromisation, co-morbidity, and individuals suffering from an overall poor general condition unable to undergo reconstructive anterior and posterior surgeries. Therefore, an alternative, less aggressive surgical method is needed for these select cases of infective spondylodiscitis. This retrospective clinical case series reports our novel surgical technique for the treatment of infective spondylodiscitis. METHODS: Between January 2005 and July 2011, among 48 patients who were diagnosed with pyogenic lumbar spondylodiscitis or tuberculosis lumbar spondylodiscitis, 10 patients (7 males and 3 females; 68 years and 48 to 78 years, respectively) underwent transpedicular curettage and drainage. The mean postoperative follow-up period was 29 months (range, 7 to 61 months). The pedicle screws were inserted to the adjacent healthy vertebrae in the usual manner. After insertion of pedicle screws, the drainage pedicle holes were made through pedicles of infected vertebra(e) in order to prevent possible seeding of infective emboli to the healthy vertebra, as the same instruments and utensils are used for both pedicle screws and the drainage holes. A minimum of 15,000 mL of sterilized normal saline was used for continuous irrigation through the pedicular pathways until the drained fluid looked clear. RESULTS: All patients' symptoms and inflammatory markers significantly improved clinically between postoperative 2 weeks and postoperative 3 months, and they were satisfied with their clinical results. Radiologically, all patients reached the spontaneous fusion between infected vertebrae and 3 patients had the screw pulled-out but they were clinically tolerable. CONCLUSIONS: We suggest that our method of transpedicular curettage and drainage is a useful technique in regards to the treatment of infectious spondylodiscitic patients, who could not tolerate conventional combined anterior and posterior surgery due to multiple co-morbidities, multiple level infectious lesions and poor general condition.

A case of right cerebellopontine-angle lesion: psychotic symptoms and magnetic resonance imaging findings.

Here, we report psychotic symptoms together with a right cerebellopontine-angle lesion. A37-year-old female patient presented with a trigeminal Schwannoma occupying the right cerebellopontine angle. Her psychotic symptoms included auditory hallucinations and delusions of persecution. T1- and T2-weighted images on magnetic resonance imaging (MRI) revealed hyperintense and hypointense areas in the right cerebellopontine angle, respectively. The clinical and neuroimaging reviews in this case suggest that sudden onset of psychotic symptoms at a mature age may be associated with a right cerebellopontine-angle lesion and that MRI should be used to evaluate possible organic bases in patients that present with psychosis.

Pulsed electromagnetic field stimulates cellular proliferation in human intervertebral disc cells.

PURPOSE: The purpose of this study is to investigate the mechanism of cellular proliferation of electromagnetic field (EMF) on human intervertebral disc (IVD) cells. MATERIALS AND METHODS: Human IVD cells were cultured three-dimensionally in alginate beads. EMF was exposed to IVD cells with 650 Ω, 1.8 millitesla magnetic flux density, 60 Hz sinusoidal wave. Cultures were divided into a control and EMF group. Cytotoxicity, DNA synthesis and proteoglycan synthesis were measured by MTT assay, [(3)H]-thymidine, and [(35)S]-sulfate incorporation. To detect phenotypical expression, reverse transcription-polymerase chain reactions (RT-PCR) were performed for aggrecan, collagen type I, and type II mRNA expression. To assess action mechanism of EMF, IVD cells were exposed to EMF with N(G)-Monomethyl-L-arginine (NMMA) and acetylsalicylic acid (ASA). RESULTS: There was no cytotoxicity in IVD cells with the EMF group in MTT assay. Cellular proliferation was observed in the EMF group (p < 0.05). There was no difference in newly synthesized proteoglycan normalized by DNA synthesis between the EMF group and the control. Cultures with EMF showed no significant change in the expression of aggrecan, type I, and type II collagen mRNA compared to the control group. Cultures with NMMA (blocker of nitric oxide) or ASA (blocker of prostaglandin E2) exposed to EMF demonstrated decreased DNA synthesis compared to control cultures without NMMA or ASA (p < 0.05). CONCLUSION: EMF stimulated DNA synthesis in human IVD cells while no significant effect on proteoglycan synthesis and chondrogenic phenotype expressions. DNA synthesis was partially mediated by nitric oxide and prostaglandin E2. EMF can be utilized to stimulate proliferation of IVD cells, which may provide efficient cell amplification in cell therapy to degenerative disc disease.