No evidence for an association between variants at the gamma-amino-n-butyric acid type A receptor beta2 locus and schizophrenia.

The alpha1/beta2/gamma2-containing heteropentamer is the most abundant gamma-amino-n-butyric acid type A receptor subtype in mammalian brains and the corresponding genes, the GABRA1, GABRB2, and GABRG2 genes, are located in chromosomal region 5q34 that several genome wide scans have implicated as a susceptibility region for schizophrenia. Given this positional and functional evidence, Lo et al. (Mol Psychiatry 2004; 9: 603-608) performed systematic linkage disequilibrium mapping of the GABAAR gene cluster on 5q34 in 130 schizophrenic patients and 170 controls, all of Chinese Han origin. In the single locus and haplotype analyses, single nucleotide polymorphisms in the GABRB2 gene showed highly significant association. The estimated effect caused by GABRB2 varied between odds ratios of 2.27 and 5.12. In order to re-examine their findings, we analyzed the most significantly associated single nucleotide polymorphism in the GABRB2 gene in a sample of 367 patients with schizophrenia and 360 controls, all of German descent. Our sample had a sufficient power to detect the effects described. Neither single marker nor haplotype analysis revealed a significant association with the disease status. Thus, our results do not support the hypothesis that genetic variation at the GABRB2 locus plays a major role in schizophrenic patients of European descent and that such variation would explain the previously observed linkage findings at this chromosomal region.

Flap adhesion and effect on postoperative complication rates using Tissuglu® in mastectomy patients.

INTRODUCTION: Post-mastectomy seroma and related complications are common problems in modern oncological surgery. Occurrence rates of up to 59% have been reported in literature. High-risk patients, that is, those who have undergone previous surgeries, present with a high body mass index, have had radiation or chemotherapy, present a particular challenge. Noninvasive measures such as fibrin-based sealants have thus far not been able to effectively reduce complications associated with fluid accumulation. A recent study using a lysine-derived urethane adhesive named TissuGlu® however, showed promising results in patients after abdominoplasty. METHODS: 32 consecutively recruited patients received a mastectomy using a gold standard mastectomy technique as well as TissuGlu® flap fixation. A control group of 173 patients, having received a gold standard mastectomy-only, was analyzed retrospectively, totaling 205 patients. Primary endpoints were post-discharge seroma formation and revision surgery/re-hospitalization. Secondary endpoints were initial seroma volume, postoperative pain, hematoma formation and day of drain removal. RESULTS: No significant difference in seroma formation was demonstrated. The revision surgery/re-hospitalization rate was reduced from 6.9 to 0%, though this did not reach significance. Significant improvement could be shown in the TissuGlu® group regarding time to drain removal (17% decrease), and hematoma formation (14% decrease). No difference was shown in postoperative pain. CONCLUSION: Although patient numbers are still small, advantages in revision surgery/re-hospitalization rate, hematoma formation as well as time to drain removal was shown for the TissuGlu® group. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

No evidence for an association between variants at the proline dehydrogenase locus and schizophrenia or bipolar affective disorder.

The proline dehydrogenase locus must be considered as a positional and functional candidate in schizophrenia. It is located in the chromosomal region of the velocardiofacial syndrome on 22q11 that is suspected to contain genes relevant to schizophrenia, and is involved in the metabolism of neurotransmitters. Positive association between single-nucleotide polymorphisms at the proline dehydrogenase locus and schizophrenia further supported the role of proline dehydrogenase in the development of schizophrenia. In order to replicate these findings, we analyzed three single-nucleotide polymorphisms in a sample comprising 299 schizophrenic patients and 300 controls. In addition, we assessed whether proline dehydrogenase also contributes to bipolar affective disorder, because chromosome 22q11 is also implicated in bipolar affective disorder. We therefore included 300 patients with bipolar affective disorder. This is the first study on a potential involvement of the proline dehydrogenase locus in bipolar affective disorder. Neither single marker nor haplotype analysis revealed an association between variants at the proline dehydrogenase locus and schizophrenia or bipolar affective disorder.

No-drain mastectomy - Preventing seroma using TissuGlu(®): A small case series.

INTRODUCTION: Post-mastectomy seroma, with an occurrence of up to 59%, is a major complication in modern oncological surgery. While drain placement is a common tool in dealing with this complication, some patients may either be incapable or unwilling to accept this course of action, requiring an alternative option for seroma prevention. A recent study using a lysine-derived urethane adhesive named TissuGlu(®) has shown promising results in mastectomy patients. CASE PRESENTATION: We used TissuGlu(®) in three patients who could not have a post-operative drain after mastectomy due to a variety of reasons. Standard mastectomy protocols were followed. Two no-drain mastectomy patients did not show any post-operative seroma formation (cases 1 and 2), while a third patient had to be aspirated twice at two (180 ml) and four weeks (60 ml) post-surgery. No complications such as hematoma, wound dehiscence or adverse reactions to the adhesive were observed. Patient satisfaction with the no-drain situation was high as post-surgical discomfort was minimal. CONCLUSION: Although one patient developed small amounts of seroma, TissuGlu(®) may present an additional option in the high risk, no-drain post-mastectomy scenario.

Seroma suppression using TissuGlu® in a high-risk patient post-mastectomy: a case report.

INTRODUCTION: Post-mastectomy seromas are a common problem in modern oncological surgery. Occurrence rates of up to 59% have been reported in the literature. High-risk patients, that is, those who have received previous surgeries, radiation or chemotherapy, present a particular challenge. Several surgical techniques, including progressive tension suture application, have shown promise. Noninvasive measures such as fibrin-based adhesives have thus far not been able to prevent seroma occurrence effectively. A recent study using a lysine-derived urethane adhesive named TissuGlu®, however, showed promising results in patients after abdominoplasty. CASE PRESENTATION: We used TissuGlu® to treat a high-risk 64-year-old female patient with a history of breast cancer and severe post-mastectomy seroma. The postsurgical period showed successful seroma suppression, without any adverse effects or complications. CONCLUSIONS: This type of adhesive should be evaluated as an alternative, less-invasive option for preventing seroma in patients after a mastectomy.

Further evidence for DYX1C1 as a susceptibility factor for dyslexia.

OBJECTIVE: Dyslexia-susceptibility-1-candidate-1 (DYX1C1) was the first gene associated with dyslexia. Since the original report of 2003, eight replication attempts have been published reporting discordant results. As the dyslexia community still considers the role of DYX1C1 unsettled, we explored the contribution of this gene in a sample of 366 trios of German descent. METHODS: To the common four markers used in previous studies, we added two new single nucleotide polymorphisms found by resequencing both the putative regulatory and coding region of the gene in randomly selected cases and controls. As linkage disequilibrium blocks of the region were not easy to define, we approached the association problem by running a transmission disequilibrium test over sliding windows of dimension 1 to 6 on consecutive markers. The significance of this test was calculated generating the empirical distribution of the global P value by simulating the data. As our study sample had a large female proband content, we also stratified our analysis by sex. RESULTS: We found statistically significant association with global corrected P value of 0.036. The three-marker haplotype G/G/G spanning rs3743205/rs3743204/rs600753 was most associated with a P value of 0.006 and odds ratio 3.7 (95% confidence interval: 1.4-9.6) in female probands. A detailed haplotype-phenotype analysis revealed that the dyslexia subphenotype short-term memory contributed mainly to the observed findings. This is in accordance with a recent short-term memory-DYX1C1 association in an independent sample of dyslexia. CONCLUSION: As significant association was proved in our sample, we could also conclude that denser maps, sex information, and well-defined subphenotypes are crucial to correctly determine the contribution of DYX1C1 to dyslexia.

Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia.

We searched for linkage disequilibrium (LD) in 137 triads with dyslexia, using markers that span the most-replicated dyslexia susceptibility region on 6p21-p22, and found association between the disease and markers within the VMP/DCDC2/KAAG1 locus. Detailed refinement of the LD region, involving sequencing and genotyping of additional markers, showed significant association within DCDC2 in single-marker and haplotype analyses. The association appeared to be strongest in severely affected patients. In a second step, the study was extended to include an independent sample of 239 triads with dyslexia, in which the association--in particular, with the severe phenotype of dyslexia--was confirmed. Our expression data showed that DCDC2, which contains a doublecortin homology domain that is possibly involved in cortical neuron migration, is expressed in the fetal and adult CNS, which--together with the hypothesized protein function--is in accordance with findings in dyslexic patients with abnormal neuronal migration and maturation.