Thymoma and hypogammaglobulinemia (Good's syndrome): a case report.

Good's syndrome is extremely rare and refers to an acquired B and T cell immunodeficiency in thymoma patients. We report a 51-year-old female thymoma patient who presented with recurrent herpes zoster, pneumonia, diarrhea and opportunistic infections. She was found to have acquired hypogammaglobulinemia with absent B cells. Despite repeat intravenous immunoglobulin replacement and antibiotic therapy, she died of bacterial pneumonia-induced acute respiratory distress syndrome. Clinicians should look for evidence of immunologic dysfunction in thymoma patients presenting with recurrent infections.     

Erratum to: Inflammation in Patients with Schizophrenia: The Therapeutic Benefits of Risperidone Plus Add-On Dextromethorphan

Journal of Neuroimmune Pharmacology -     

A Placebo-Controlled Trial of Dextromethorphan as an Adjunct in Opioid-Dependent Patients Undergoing Methadone Maintenance Treatment

Background:

Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT).

Methods:

Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor–β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect.

Results:

After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different.

Conclusions:

We provide evidence—decreased concomitant heroin use—of low-dose add-on DM’s efficacy for treating opioid-dependent patients undergoing MMT.     

Disproportionate Reduction of Serotonin Transporter May Predict the Response and Adherence to Antidepressants in Patients with Major Depressive Disorder: A Positron Emission Tomography Study with 4-[18F]-ADAM

Background:

Many lines of evidence suggest the role of serotonin transporter (SERT)-mediated reuptake of serotonin in the pathophysiology and treatment of major depressive disorder (MDD). This study aimed to examine whether the pretreatment of SERT binding potential or SERT binding ratio between terminal projection regions relative to the midbrain raphe nuclei was associated with treatment outcomes to SERT-targeted antidepressants.

Methods:

We recruited 39 antidepressant-naïve patients with MDD and 39 heathy controls. Positron emission tomography with N,N-dimethyl-2-(2-amino-4-[¹⁸F]fluorophenylthio)benzylamine (4-[¹⁸F]-ADAM) was used to measure in vivo SERT availability prior to antidepressant treatment. The 21-item Hamilton Depression Rating Scale (HDRS) was use to assess the severity of depression from baseline to week 6. All the patients with MDD had HDRS scores of 18 or more.

Results:

Pretreatment SERT binding in the thalamus and striatum positively correlated with an early reduction in HDRS scores at week 3. Nonresponders and dropout patients showed a proportionate reduction in SERT binding in the terminal projection regions and midbrain compared to healthy controls. In contrast, a disproportionate reduction in SERT binding in the terminal projection regions relative to midbrain was observed in responders.

Conclusions:

The results of this study suggested that a disproportionate reduction in SERT binding between terminal projection regions and midbrain may predict better treatment outcomes in patients with MDD.     

Generalized Anxiety Disorder,Comorbid Major Depression and Heart Rate Variability: A Case-Control Study in Taiwan

Objective

Decreased heart rate variability (HRV) has been reported in generalized anxiety disorder (GAD), but the results are mixed. Little is known about the impact of comorbid major depression (MD) on HRV in GAD patients. Both issues necessitate further investigation.

Methods

Twenty unmedicated, physically healthy GAD patients, 20 GAD patients with a secondary diagnosis of MD, 40 MD patients and 60 matched controls were recruited. We used the Hamilton Anxiety Rating Scale and the Hamilton Depression Rating Scale to assess anxiety and depression severity, respectively. Cardiac autonomic function was evaluated by measuring HRV parameters. Frequency-domain indices of HRV were obtained.

Results

Three patient groups had more anxiety and depression symptoms than control subjects, but heart rates (HRs) were significantly elevated only in GAD patients with comorbid depression. Relative to controls, GAD patients had reduced HRV while GAD patients with comorbid depression displayed the greatest reductions in HRV among three patients groups. Correlation analyses revealed anxiety/depression severity significantly associated with HRs, variance, LF-HRV and HF-HRV. However, separately analyzing among individual groups and adjusting for HRV-associated covariables rendered the correlations non-significant.

Conclusion

Our results suggest that reduction in HRV is a psychophysiological marker of GAD and individuals with comorbid GAD and MD may be distinguished based on psychophysiological correlates (for example, HF-HRV) from non-comorbid GAD patients. Taken into account that comorbid depression may confer increased risks for cardiovascular events in GAD patients, this subgroup of GAD patients may benefit better from cardiovascular risk reduction strategies.     

CEACAM5 has different expression patterns in gastric non-neoplastic and neoplastic lesions and cytoplasmic staining is a marker for evaluation of tumor progression in gastric adenocarcinoma

Objective

The aim of this study was to investigate the expression patterns of CEACAM5 in non-neoplastic and neoplastic gastric lesions, as well as its application in the differential diagnosis and its relationship with tumor progression.

Methods

CEACAM5 expression was detected by immunohistochemical staining in the serial sections of the gastric neoplastic and non-neoplastic lesions. The impacts of CEACAM5 expression patterns on tumor progression were evaluated by statistics, the clinical and pathological data included sex, age, tumor extension, lymph node involvement and tumor staging.

Results

There was no CEACAM5 expression in normal gastric epithelial cells. In hyperplastic polyps, CEACAM5 was expressed with apical membranous staining in the hyperplastic and prolonged gastric pit adjacent to the surface. Intestinal metaplasia (IM) expressed CEACAM5 mainly with membranous pattern, and some cases showed membranous staining mixed with cytoplasmic staining. GIN expressed CEACAM5 mainly with membranous staining, but the mixed staining of cytoplasmic and membranous patterns increased, and especially in the high grade GIN, cytoplasmic staining of CEACAM5 began to occur. Compared with IM and GIN, CEACAM5 expression patterns of hyperplastic polyp showed a significant difference (P = 0.000). IM, low grade GIN and the whole GIN showed no significant difference in CEACAM5 expression patterns (P = 0.355), but IM and high grade GIN showed a significant difference (P = 0.027). There was a significant difference between low and high grade GIN (P = 0.002). GIN and well-differentiated carcinomas showed no significant difference (P = 0.070), but low grade GIN and well differentiated carcinomas showed a significant difference (P = 0.006). In gastric adenocarcinomas, CEACAM5 expression patterns showed a significant difference in tumor grading (P = 0.010) and Laurén classification (P = 0.001). In histological grading, well differentiated carcinomas showed more membranous staining than moderately and poorly differentiated, and more cytoplasmic CEACAM5 staining was detected in moderately and poorly differentiated carcinomas. Similar to that, in Laurén classification, intestinal carcinomas showed more membranous staining, and diffuse carcinomas showed more cytoplasmic staining. Moreover, CEACAM5 expression patterns showed a significant difference in tumor extension (P = 0.012), lymph node involvement (P = 0.015) and tumor staging (P = 0.002), suggesting that CEACAM5 should be involved in tumor progression. In advanced carcinomas, CEACAM5 was expressed with more cytoplasmic staining regardless of the histological classification.

Conclusion

CEACAM5 had different expression patterns in gastric non-neoplastic and neoplastic lesions. The CEACAM5 expression patterns were associated with tumor progression. Membranous staining of CEACAM5 might be a marker of premalignancy in gastric lesions, and cytoplasmic CEACAM5 might enhance tumor invasion and migration and be an evaluated marker for progressive and advanced gastric cancer. Also, it might be useful for the differential diagnosis of gastric premalignant lesions.     

Possible interaction of alcohol dehydrogenase and aldehyde dehydrogenase genes with the dopamine D2 receptor gene in anxiety-depressive alcohol dependence

BACKGROUND: The role of the dopamine D2 receptor (DRD2) gene in the development of alcohol abuse or dependence is controversial. The controversy is due in part to the disparate definitions pertaining to the control groups used and to the definitions of subtypes in alcohol dependence. In the Han Chinese population, the alcohol dehydrogenase 1B*2/*2 (ADH1B*2/*2) genotype and the aldehyde dehydrogenase 2*2 (ALDH2*2) allele have been considered as protective factors against alcohol abuse or dependence. Moreover, the ADH1B and ALDH2 genes might be involved in dopamine metabolism. We hypothesized that the ADH1B and ALDH2 genes might interact with the DRD2 gene and that the association between the DRD2 gene and alcohol dependence might be affected by different ADH1B and ALDH2 genotypes. This study examined whether the DRD2 gene is associated with specific subtypes of alcohol dependence and evaluated the relationship between the DRD2 gene and alcohol-metabolizing genes in a specific subtype of alcohol dependence. METHODS: Of the 465 Han Chinese subjects who were recruited for the study, 71 were classified with pure alcohol dependence, 113 with both alcohol dependence and anxiety-depression (ANX/DEP ALC), and 129 with anxiety-depression but without alcohol dependence (ANX/DEP). The remaining 152 subjects were supernormal controls. All subjects were interviewed with the Chinese version of the modified Schedule of Affective Disorders and Schizophrenia-Lifetime; all alcohol dependence, anxiety, and major depressive diagnoses were made according to DSM-IV criteria. RESULTS: The DRD2 gene was not found to be associated with pure alcohol dependence or ANX/DEP, but was found to be associated with ANX/DEP ALC. Furthermore, the association between the DRD2 gene and ANX/DEP ALC was shown to be under the control of the ALDH2*1/*1 and ADH1B*1/*2 genotypes. CONCLUSIONS: ANX/DEP ALC is a specific subtype of alcohol dependence. Because ANX/DEP ALC was associated with the DRD2 gene only under the stratification of ADH1B*1/*2 or ALDH2*1/*1, the DRD2 gene might interact with the ADH1B gene and the ALDH2 gene, respectively, in the development of ANX/DEP ALC in the Taiwan Han Chinese population.     

Influence of the aspect ratio of bioactive nanofillers on rheological behavior of PMMA-based orthopedic materials

In this investigation, calcium-deficient hydroxyapatite (CDHA) nanocrystals with needle-like geometry were synthesized and incorporated with Poly(methyl methacrylate), PMMA, to form CDHA-PMMA nanocomposites. Rheological behaviors of the PMMA-CDHA melting suspensions were systematically investigated in terms of solid loading and aspect ratio of the CDHA nanoparticles. The maximum solid loadings of nano-CDHA particles with aspect ratios of 7.2, 10.4, and 17 were determined to be 28, 31, and 57%, respectively. An increase in solid concentrations causes pronounced shear-thinning behavior. This result suggests that a strong interaction, including Van der Waals attraction and mechanical interlocking, between the nano-CDHA particles makes the nanocomposite mixture more non-Newtonian. Furthermore, it was found that packing efficiency and yield strength in the suspension were strongly influenced by the aspect ratio, especially above the critical value of 8.8. The obtained critical aspect ratio and solid content provide not only appropriate design in the PMMA-CDHA polymeric suspension for fabrication process but also optimal conditions for the fabrication of orthopedic devices via injection molding or extrusion.     

Neither single-marker nor haplotype analyses support an association between monoamine oxidase A gene and bipolar disorder

Monoamine oxidase A (MAOA) abnormality has been suggested as a crucial factor in the pathogenesis of mood disorder, because MAOA is associated with the metabolism of monoamines such as serotonin and norepinephrine. Various MAOA gene polymorphisms have been investigated for possible associations with bipolar disorder (BD), but the results are controversial. Our goal was to investigate whether MAOA gene polymorphisms, especially the promoter uVNTR polymorphism and the EcoRV polymorphism, are associated either with BD or with different clinical subtypes of BD. A total of 714 Han Chinese subjects in Taiwan (305 controls and 409 BD patients) were recruited for study. All subjects were interviewed with the Chinese Version of the Modified Schedule of Affective Disorders and Schizophrenia-Lifetime; BD was diagnosed according to DSM-IV criteria. Genotyping for MAOA polymorphisms was performed using PCR and restriction fragment length polymorphism. The MAOA promoter polymorphisms uVNTR and EcoRV were not associated with BD or any of its subtypes, in either the frequencies of alleles or genotypes. In multiple logistic regression and haplotype frequency analysis, we confirmed these negative results in both females and males. Our results suggest that MAOA polymorphisms do not play a major role in pathogenesis of BD or its clinical subtypes in Han Chinese.