Allelic variants of <Emphasis Type="Italic">SNAP25</Emphasis> in a family-based sample of ADHD

Summary Altered neurotransmission has been suggested to be a crucial factor in the pathophysiology of attention-deficit/hyperactivity disorder ADHD. Subsequently genes encoding for synaptic proteins have been investigated in candidate gene studies. These proteins mediate the release of neurotransmitters into the synaptic cleft in the process of signal transduction by forming a transient complex, enabling the junction of vesicle and synaptic membrane. One of the core proteins of this complex is the synaptosomal-associated protein 25 (SNAP25). It is one of the most validated candidate genes in ADHD according to meta-analyses. However, differing results were observed in previous studies, some of which were not able to observe association with ADHD. In this study we aimed to investigate association of genetic variants of SNAP25 located in the putative promoter region of SNAP25 and a SNP in intron 8, previously reported to associated with ADHD. A family based design was applied to detect preferential transmission of genetic variants. In our German ADHD sample no preferential transmission of either variant could be observed. Further investigation considering sub-sample analysis regarding response to D-amphetamine could enlight the role of SNAP25 in ADHD. Correspondence: Tobias J. Renner, Department of Child and Adolescent Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany     

Healing of intrabony defects following surgical treatment with or without an Er:YAG laser

AIM: The aim of this controlled, parallel design clinical study was to compare the healing of intrabony periodontal defects following treatment with access flap surgery with and without debridement with an Er:YAG laser. METHODS: Twenty-three patients each of whom exhibited one deep intrabony defect were randomly treated with either access flap surgery followed by root surface and defect debridement using an Er:YAG laser (KEY3) (160 mJ, 10 Hz) (test), or with access flap surgery followed by root surface and defect debridement using hand and ultrasonic instruments (control). The following clinical parameters were recorded at baseline and at 6 months: plaque index; gingival index; bleeding on probing; probing depth (PD); gingival recession; and clinical attachment level (CAL). The primary outcome variable was CAL. No statistically significant differences between the groups were found at baseline. RESULTS: No serious adverse events were observed after any of the treatments. The results have shown that in the test group the PD decreased from 7.8+/-1.3 to 4.1+/-1.3 mm (p<0.001) and the CAL changed from 9.8+/-2.9 to 7.2+/-2.5 mm (p<0.001). In the control group the PD decreased from 7.8+/-0.8 to 4.6+/-1.6 mm (p<0.001) and the CAL changed from 9.2+/-1.2 to 7.7+/-1.6 mm (p<0.01). The test group displayed a higher tendency for CAL gain, although this tendency did not prove to be statistically significant. CONCLUSION: Within the limits of the present study, it can be concluded that: (i) at 6 months following treatment both therapies led to significant improvements of the investigated clinical parameters, and (ii) an Er:YAG laser may represent a suitable alternative for defect and root surface debridement in conjunction with periodontal surgery.     

Complications and Toxicity After Abdominal and Pelvic Hypoxic Stop-Flow Perfusion Chemotherapy: Incidence and Assessment of Risk Factors

Background

Controversial results regarding the efficacy and toxicity of hypoxic abdominal and pelvic stop-flow perfusion chemotherapy (SFP) have been reported in relatively small series. Hence, because adequate assessment of its benefit in large homogenous cohorts is missing, acceptable morbidity should initially be assured in a series of adequate size. Additionally, risk factors should be assessed for eventual patient selection.

Methods

The morbidity of abdominal and pelvic SFP performed on a miscellaneous group of patients in our institute was analyzed and potential risk factors for adverse events were evaluated.

Results

Seventy abdominal (n?=?42) and pelvic (n?=?28) SFP were performed on 55 patients. In total, 28 adverse effects were observed after 30?% of the procedures. Severe (grade 3) adverse events were recorded only after 4?% of the procedures, while treatment-related life-threatening events and deaths were not present. Abdominal procedures when compared with pelvic ones were associated with increased systemic toxicity (36 vs. 7?%, p?=?0.005). Advanced age, gender, prior chemotherapy and/or radiotherapy, limited experience, repeated procedure, drug choice and omission of hemofiltration after SFP completion were not associated with statistically significant increase of procedures with overall or systemic adverse events.

Conclusions

In the present series, abdominal and pelvic SFP was associated with an acceptable morbidity, which was mostly mild or moderate. Abdominal procedures were associated with increased toxicity. This procedure seems to be repeatable and also well tolerated both by elderly patients and by patients who had undergone prior chemotherapy and/or radiotherapy, while hemofiltration does not appear to decrease the incidence of systemic toxicity.     

Hypercoagulable States in Patients with Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) patients have an increased risk for venous thromboembolism, mainly portal venous thrombosis (PVT). The aim of this study was to assess the role of acquired and hereditary thrombotic risk factors in HCC patients. Thirty-one patients with HCC, 30 patients with cirrhosis but without HCC or PVT, and 48 matched healthy controls were studied. Mean levels of plasma protein C, protein S, antithrombin, and serum lipoprotein (a) were significantly lower in patients with HCC and in the cirrhotic group compared to the healthy controls. Mean serum homocysteine levels were significantly higher in patients with HCC compared to cirrhotics and healthy controls. The prevalence of activated protein C resistance, factor V Leiden mutation, prothrombin gene mutation G20210GA, and C677T methylenetetrahydrofolate reductase polymorphism was not significantly different among the three groups. In conclusion, thrombophilic defects are common in HCC patients and they might contribute to the observed thrombotic complications in this malignancy.     

Effects of non-HLA gene polymorphisms on development of islet autoimmunity and type 1 diabetes in a population with high-risk HLA-DR,DQ genotypes

We assessed the effects of non-HLA gene polymorphisms on the risk of islet autoimmunity (IA) and progression to type 1 diabetes in the Diabetes Autoimmunity Study in the Young. A total of 1,743 non-Hispanic, white children were included: 861 first-degree relatives and 882 general population children identified as having high-risk HLA-DR/DQ genotypes for type 1 diabetes. Of those, 109 developed IA and 61 progressed to diabetes. Study participants were genotyped for 20 non-HLA polymorphisms, previously confirmed as type 1 diabetes susceptibility loci. PTPN22 and UBASH3A predicted both IA and diabetes in regression models controlling for family history of type 1 diabetes and presence of HLA-DR3/4-DQB1*0302 genotype. In addition, PTPN2 predicted IA whereas INS predicted type 1 diabetes. The final multivariate regression models for both IA and type 1 diabetes included PTPN22, UBASH3A, and INS, in addition to family history of type 1 diabetes and HLA-DR3/4. In general population children, the most frequent combinations including these five significant predictors conferred hazard ratio of up to 13 for IA and >40 for type 1 diabetes. Non-HLA susceptibility alleles may help estimate risk for development of type 1 diabetes in the general population. These findings require replication in different populations.     

Effects of methylphenidate on olfaction and frontal and temporal brain oxygenation in children with ADHD

Objective

Olfaction and attention-deficit-/hyperactivity disorder (ADHD) are mediated by dopamine metabolism and fronto-temporal functioning converging in recent findings of increased olfactory sensitivity in children with ADHD modulated by methylphenidate (MPH) and altered frontal and temporal oxygenation in adults with ADHD.

Method

We investigated olfactory sensitivity, discrimination, and identification (Sniffin’ Sticks) in 27 children and adolescents with ADHD under chronic MPH medication and after a wash-out period of at least 14 half-lives in balanced order and 22 controls comparable for handedness, age, and intelligence. In addition, inferior frontal and temporal oxygenation was measured by means of functional near-infrared spectroscopy (fNIRS) during the presentation of 2-phenylethanol. Group differences in regard to sex distribution were statistically controlled for by analysis of covariance.

Results

Patients did not differ from controls in any olfactory domain under treatment with MPH. Cessation of medication led to a significant increase in olfactory discrimination. Controls displayed typical inferior frontal and temporal brain activity in response to passive olfactory stimulation, while brain oxygenation was diminished in the patient group when assessed without medication. Under medication ADHD patients showed a trend for a normalisation of brain activity in the temporal cortex.

Conclusions

The here reported effects of MPH cessation on olfactory discrimination and frontal and temporal oxygenation along with previous findings of increased olfactory sensitivity in medication-naïve ADHD children and its normalisation under chronic MPH treatment lead to the conclusion that MPH exerts differential chronic effects vs. acute cessation effects on altered olfactory function in ADHD. These effects are most probably mediated by modulation of the dopaminergic system.