Mirtazapine for patients with alcohol dependence and comorbid depressive disorders: a multicentre, open label study

Major depressive disorder and alcohol dependence are common and serious mental illnesses. There is a great interest in discovering useful treatments for both mood symptoms and alcohol abuse in those patients with depressive disorders and comorbid alcohol dependence. The primary purpose of this study was to evaluate the effectiveness and tolerability of mirtazapine for the treatment of patients with alcohol dependence comorbid with a depressive disorder in an open label, naturalistic multicentre treatment setting. The 17-item Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS) and the Clinical Global Impression-Severity (CGI-S) scale were measured at baseline and at weeks 4 and 8 for the assessment of treatment effectiveness. Alcohol craving was measured using the Obsessive Compulsive Drinking Scale (OCDS) and the Visual Analog Scale for Craving (VAS). This study showed a statistically significant reduction of the scores on the HDRS (13.9+/-7.3, p<0.0001), HARS (10.8+/-7.2, p<0.0001) and the CGI-S (1.7+/-1.0, p<0.0001) from baseline to the endpoint (week 8). The OCDS and VAS scores were also decreased significantly by 42.3% and 53.2% (9.0+/-10.0, p<0.0001; 2.5+/-2.4, p<0.0001, respectively). The number of patients with a 50% reduction or more in the HDRS and HARS scores was 103 (72.0%) and 106 (74.1%) at the endpoint, respectively. Adverse events related to mirtazapine were observed in 10% or more of the patients in this study. In conclusion, the results from this naturalistic study suggest that the use of mirtazapine for the patients with alcohol dependence comorbid with depressive disorder is accompanied by clinical improvement in their mood and alcohol craving.     

Loss of Raf-1 kinase inhibitor protein expression is associated with lymph node metastasis in papillary thyroid cancer

Objective

Raf-1 kinase inhibitor protein has potential as a molecular determinant of tumor metastasis and may serve as a prognostic marker. The aim of this study is to analyze the correlation between Raf-1 kinase inhibitor protein expression and the clinicopathologic characteristics of papillary thyroid cancer.

Study Design

Immunohistochemical analysis.

Setting

Tertiary care teaching hospital.

Subjects and Methods

Fifty-nine patients with papillary thyroid cancer underwent total thyroidectomy and central neck dissection. Using specimens from total thyroidectomy and central neck dissection, we performed immunohistochemistry for Raf-1 kinase inhibitor protein and evaluated associations between Raf-1 kinase inhibitor protein expression and lymph node metastasis, tumor size, number of tumors, extrathyroidal invasion, angiolymphatic invasion, and status of the tumor border.

Results

We found significantly low Raf-1 kinase inhibitor protein expression in papillary thyroid cancer with lymph node metastasis. However, Raf-1 kinase inhibitor protein expression was not associated with tumor size, multifocality, extrathyroidal invasion, or status of the tumor border.

Conclusion

The loss of Raf-1 kinase inhibitor protein expression is associated with lymph node metastasis of papillary thyroid cancer but not with the progression of primary tumors.     

Validation of clinical AJCC/UICC TNM staging system for hepatocellular carcinoma: analysis of 5,613 cases from a medical center in southern Taiwan

This study was aimed to validate the 5th and 6th editions of tumor-node-metastasis (TNM) system for patients with hepatocellular carcinoma (HCC), and attempted to improve prognostic stratification by modifying the 6th edition according to vascular invasion and tumor size. From 1986 to 2002, a total of 5,613 HCC cases from Kaohsiung Chang Gung Memorial Hospital in southern Taiwan were enrolled. The 6th edition was modified by dividing stage I into stages IA (single tumor, < or =2cm) and IB (single tumor, >2cm), and by dividing stage II into IIA (multiple tumors, none >5cm) and IIB (tumor with segmental macro vascular invasion). The Akaike information criteria (AIC), within a Cox proportional hazard regression model were used; lower AIC value indicated a better discriminatory ability for staging system. The 1-, 3-, 5-, and 7-year overall survival rates were 45.6, 25.9, 17.9, and 13.4%, respectively. Significant differences in survival curve existed in the 5th, 6th, and modified 6th edition TNM systems. For the modified 6th edition TNM, survival differed significantly between stages IA and IB, and between stage IIA and IIB. The AIC values of 5th (72,328), 6th (72,188), modified 6th (71,991) edition TNM system were decreasing. This investigation demonstrated better prognostic stratifications for the 6th edition than the 5th edition TNM staging system. Moreover, the modified 6th edition staging system demonstrated better prognostic prediction than the former two. Pretreatment staging and simple classification of current modified 6th edition TNM staging can be applied to all HCC patients and are clinically useful.     

Relationships between 24-Hour Blood Pressures, Subcortical Ischemic Lesions, and Cognitive Impairment

Background and Purpose

The most important treatment for subcortical vascular dementia (SVaD) is controlling the blood pressure (BP). However, the few studies that have investigated the relationships between diurnal BP rhythm and subcortical ischemic vascular cognitive impairment have produced inconclusive results. In the study presented here, the 24-hour BP values of three groups of subjects-patients with subcortical vascular mild cognitive impairment (SvMCI), patients with SVaD, and normal controls-were compared using working criteria and 24-hour ambulatory BP (ABP) monitoring.

Methods

The subjects (42 patients with SVaD, 37 patients with SvMCI, and 30 controls) were selected according to the study''s inclusion/exclusion criteria. All subjects underwent brain magnetic resonance (MR) imaging and MR angiography, detailed neuropsychological testing, and 24-hour ABP monitoring.

Results

The prevalence of nondippers differed markedly between the control group and both the SVaD and SvMCI groups. Loss of nocturnal dipping was significantly associated with SVaD [odds ratio (OR), 4.827; 95% confidence interval (CI), 1.07-12.05].

Conclusions

It was found that SVaD is associated with loss of nocturnal BP dipping combined with increased pulse pressure and systolic BP (SBP) variability. Correction of these factors could therefore be important in the prevention of SVaD, independent of measures used to reduce BP.     

Localization of Broca's Area Using Functional MR Imaging: Quantitative Evaluation of Paradigms

Objective

Functional magnetic resonance imaging (fMRI) is frequently used to localize language areas in a non-invasive manner. Various paradigms for presurgical localization of language areas have been developed, but a systematic quantitative evaluation of the efficiency of those paradigms has not been performed. In the present study, the authors analyzed different language paradigms to see which paradigm is most efficient in localizing frontal language areas.

Methods

Five men and five women with no neurological deficits participated (mean age, 24 years) in this study. All volunteers were right-handed. Each subject performed 4 tasks, including fixation (Fix), sentence reading (SR), pseudoword reading (PR), and word generation (WG). Fixation and pseudoword reading were used as contrasts. The functional area was defined as the area(s) with a t-value of more than 3.92 in fMRI with different tasks. To apply an anatomical constraint, we used a brain atlas mapping system, which is available in AFNI, to define the anatomical frontal language area. The numbers of voxels in overlapped area between anatomical and functional area were individually counted in the frontal expressive language area.

Results

Of the various combinations, the word generation task was most effective in delineating the frontal expressive language area when fixation was used as a contrast (p<0.05). The sensitivity of this test for localizing Broca''s area was 81% and specificity was 70%.

Conclusion

Word generation versus fixation could effectively and reliably delineate the frontal language area. A customized effective paradigm should be analyzed in order to evaluate various language functions.     

The effect of postoperative immobilization on short-segment fixation without bone grafting for unstable fractures of thoracolumbar spine

Background:

Controversy regarding the fixation level for the management of unstable thoracolumbar spine fractures exists. Often poor results are reported with short-segment fixation. The present study is undertaken to compare the effect of fixation level and variable duration of postoperative immobilization on the outcome of unstable thoracolumbar burst fractures treated by posterior stabilization without bone grafting.

Patients and Methods:

A randomized, prospective, and consecutive series was conducted at a tertiary level medical center. Thirty-six neurologically intact (Frankel type E) thoracolumbar burst fracture patients admitted at our institute between February 2003 and December 2005 were randomly divided into three groups. Group I (n = 15) and II (n = 11) patients were treated by short-segment fixation, while Group III (n = 10) patients were treated by long-segment fixation. In Group I ambulation was delayed to 10th-14th postoperative day, while group II and III patients were mobilized on third postoperative day. Anterior body height loss (ABHL) percentage and increase in kyphosis as measured by Cobb''s angle were calculated preoperatively, postoperatively, and at follow-up. Denis Pain Scale and Work Scales were obtained during follow-up.

Results:

Mean follow-up was 13.7 months (range 3-27 months). At the final follow-up the mean ABHL was 4.73% in group I compared with 16.2% in group II and 6.20% in group III. The mean Cobb''s angle loss was 1.8° in group I compared with 5.91° in group II and 2.3° in group III. The ABHL difference between groups I and II was significant (P = 0.0002), while between groups I and III was not significant (P = 0.49).

Conclusion:

The short-segment fixation with amenable delayed ambulation is a valid option for the management of thoracolumbar burst fractures, as radiological results are comparable to that of long-segment fixation with the advantage of preserving maximum number of motion segments.     

The relationship between online game addiction and aggression, self-control and narcissistic personality traits

OBJECTIVES: This study aimed to explore the relationship between online game addiction and aggression, self-control, and narcissistic personality traits, which are known as the psychological characteristics linked to "at-risk" populations for online game addiction. METHOD: A total of 1471 online game users (males 82.7%, females 17.3%, mean age 21.30+/-4.96) participated in this study and were asked to complete several self-report measures using an online response method. Questionnaires included demographic information and game use-related characteristics of the samples, the online game addiction scale (modified from Young's Internet addiction scale), the Buss-Perry aggression questionnaire, a self-control scale, and the narcissistic personality disorder scale. RESULTS: Our results indicated that aggression and narcissistic personality traits are positively correlated with online game addiction, whereas self-control is negatively correlated with online game addiction (p<0.001). In addition, a multiple regression analysis revealed that the extent of online game addiction could be predicted based on the person's narcissistic personality traits, aggression, self-control, interpersonal relationship, and occupation. However, only 20% of the variance in behavioral consequences was explained with the model. CONCLUSION: An interesting profile has emerged from the results of this study, suggesting that certain psychological characteristics such as aggression, self-control, and narcissistic personality traits may predispose some individuals to become addicted to online games. This result will deepen our understanding of the "at-risk" population for online game addiction and provide basic information that can contribute to developing a prevention program for people who are addicted to online games.     

Potentiation of the NMDA receptor in the treatment of schizophrenia: focused on the glycine site

N-methyl-D-aspartate receptor (NMDAR) hypo-function theory of schizophrenia proposes that impairment in NMDAR function be associated with the pathophysiology of schizophrenia and suggests that enhancement of the receptor function may produce efficacy for schizophrenia. Consistent with this theory, for the last decade, clinical trials have demonstrated that the enhancement of NMDAR function by potentiating the glycine site of the receptor is efficacious in the treatment of schizophrenia. Full agonists of the glycine site, glycine and D-serine and a glycine transporter-1 inhibitor, sarcosine, added to antipsychotic drugs, have been shown to be effective in the treatment of negative symptoms and possibly cognitive symptoms without significantly affecting the positive symptoms of schizophrenia. A partial agonist of the glycine site, D-cycloserine, added to antipsychotic drugs, can be effective for the negative symptoms at the therapeutic doses. However, these drugs have not shown clinical efficacy when added to clozapine, suggesting that the interactions of clozapine and the glycine site potentiators may be different from those of other antipsychotic drugs and the potentiators. This article suggests that the glycine site potentiators may produce efficacy for negative and cognitive symptoms by blocking apoptosis-like neuropathological processes in patients with chronic schizophrenia and thereby can deter progressive deterioration of the disorder. This article proposes a polypharmacy of glycine site potentiators augmented with antipsychotic drugs to control positive and negative symptoms in a synergistic manner and block deterioration in schizophrenia. Since the NMDAR complex consists of multiple sites modulating receptor functions, the efficacy of glycine site potentiators for schizophrenia suggests the possibility that manipulation of other modulating sites of the NMDAR can also be efficacious in the treatment of schizophrenia.