Altered interregional molecular associations of the serotonin transporter in attention deficit/hyperactivity disorder assessed with PET

Altered serotonergic neurotransmission has been found to cause impulsive and aggressive behavior, as well as increased motor activity, all exemplifying key symptoms of ADHD. The main objectives of this positron emission tomography (PET) study were to investigate the serotonin transporter binding potential (SERT BP_ND) in patients with ADHD and to assess associations of SERT BP_ND between the brain regions. 25 medication‐free patients with ADHD (age ± SD; 32.39 ± 10.15; 10 females) without any psychiatric comorbidity and 25 age and sex matched healthy control subjects (33.74 ± 10.20) were measured once with PET and the highly selective and specific radioligand [¹¹C]DASB. SERT BP_ND maps in nine a priori defined ROIs exhibiting high SERT binding were compared between groups by means of a linear mixed model. Finally, adopted from structural and functional connectivity analyses, we performed correlational analyses using regional SERT binding potentials to examine molecular interregional associations between all selected ROIs. We observed significant differences in the interregional correlations between the precuneus and the hippocampus in patients with ADHD compared to healthy controls, using SERT BP_ND of the investigated ROIs (P < 0.05; Bonferroni corrected). When correlating SERT BP_ND and age in the ADHD and the healthy control group, we confirmed an age‐related decline in brain SERT binding in the thalamus and insula (R² = 0.284, R² = 0.167, Ps < 0.05; Bonferroni corrected). The results show significantly different interregional molecular associations of the SERT expression for the precuneus with hippocampus in patients with ADHD, indicating presumably altered functional coupling. Altered interregional coupling between brain regions might be a sensitive approach to demonstrate functional and molecular alterations in psychiatric conditions. Hum Brain Mapp 38:792–802, 2017. © 2016 Wiley Periodicals, Inc.     

Right ventricular adaptation to pulmonary pressure load in patients with chronic thromboembolic pulmonary hypertension before and after successful pulmonary endarterectomy - a cardiovascular magnetic resonance study

Background

The aim of the study was to characterize RV adaptation to varying loading conditions in patients with chronic thromboembolic hypertension (CTEPH) before and after pulmonary endarterectomy (PEA). Nearly 4% of patients with pulmonary embolism develop CTEPH. PEA offers a cure with excellent outcome. By use of cardiovascular magnetic resonance (CMR) combined with hemodynamic measurements pulmonary arterial elastance (E_{a-pulm_i}), end-systolic right ventricular elastance (E_{es-RV_i}) and ventriculo-arterial coupling (E_{a-pulm_i}/E_{es-RV_i}) can be studied before and after PEA.

Methods

Sixty-five patients (mean age 41 ± 12 years, 28 female) underwent CMR pre- and post-PEA. Ejection fraction (EF), end-diastolic (EDV_i), end-systolic (ESV_i), and stroke (SV_i) volumes were indexed for body surface area. E_{a-pulm_i} was calculated as pulmonary artery mean pressure (mPAP)/SV_i, and E_{es-RV_i} as mPAP/ESV_i.

Results

mPAP decreased from 47 ± 12 to 25 ± 9 mmHg, p =0.0001. E_{a-pulm_i} was increased before PEA and normalized afterwards (2.8 ± 2.1 vs. 0.85 ± 0.4 mmHg/ml/m², p =0.0001). E_{es-RV_i} was depressed before and after PEA (0.72 ± 0.27 vs. 0.66 ± 0.3 mmHg/ml/m², p =0.13). EF improved from 25 ± 12% to 46 ± 10%, p =0.0001, because ventriculo-arterial coupling was restored (4.2 ± 3 vs. 1.4 ± 0.6, p =0.0001). EDV_i and ESVi mproved significantly (EDV_i 92 ± 32 to 72 ± 23 ml, p =0.0001; ESV_i 69 ± 31 to 41 ± 18 ml, p =0.0001).

Conclusion

RV function is largely determined by afterload and returns to normal once afterload is normalized. This is paralleled by a significant improvement of CMR indices of right ventricular remodelling.     

Outcome and treatment quality of transfer primary percutaneous intervention in older patients with acute ST-elevation myocardial infarction (STEMI)

The aim of this study was to evaluate the outcome and treatment quality of transfer percutaneous coronary intervention (PCI) in older patients with acute STEMI. In this prospective study all patients with diagnosed acute (pain-to-balloon ≤ 12 h) STEMI transferred to our institution for primary PCI (n = 400) between January 2005 and October 2007 were under investigation. Overall 125 older patients with age ≥70 years were included (mean age 77.5 ± 4.9 years; 77 males). Pre-hospital delays were more common in older patients with longer pain-to-balloon: median (range) = 85 (5-629) vs. 66 (1-688) p = 0.031, and pain-to-first medical-contact-times: median: 206 (84-711) vs. 172 (45-720); p = 0.001. A trend towards a higher (non-significant) rate of major 5/125 (5%) vs. 5/275 (1.8%), p = 0.195 and minor 10/125 (8%) vs. 14/275 (5.1%). p = 0.256 bleeding complications in older patients was evident. In-hospital mortality was significantly higher in older patients compared to the younger patients group: 13/125, 10.4% vs. 8/275, 2.9%, p = 0.002). Overall mortality at 30-day follow-up was 11.2% in older and 3.3% in younger patients: 14/125 vs. 9/275, p = 0.002. Transfer PCI is an effective treatment strategy for older patients with acute ST-elevation myocardial infarction. Overall-30-day mortality in older STEMI-patients transferred for primary PCI is comparably low.     

Comparative analysis of cathepsin l,cathepsin d,and collagenase messenger rna expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis,by in situ hybridization

Objective. To compare the expression of cathepsin L, cathepsin D, and collagenase messenger RNA (mRNA) in synovial specimens from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Methods. The expression of cathepsins L and D as well as collagenase mRNA in synovial tissues from 8 patients with RA, 6 patients with OA, and 2 patients with noninflamed joints was evaluated using in situ hybridization with digoxigenin-labeled RNA probes. Results. Both RA and OA synovial tissue expressed cathepsins L and D as well as collagenase mRNA. The expression of the cathepsins was markedly higher in interstitial regions and, to some extent, in perivascular infiltrates of RA synovial tissue compared with OA specimens. Conclusion. Cathepsins L and D mRNA are expressed differently in RA and OA synovial tissues, supporting the concept that these enzymes may contribute to the influx of mononuclear cells into RA synovium. Moreover, the data reveal that the expression of collagenase and cathepsins in RA and OA synovial lining is otherwise largely similar, and suggest that the adhesion of synovial cells to cartilage mediates the invasive destructive process in RA.     

Inter-study reproducibility of cardiovascular magnetic resonance myocardial feature tracking

Background

Cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) is a recently described method of post processing routine cine acquisitions which aims to provide quantitative measurements of circumferentially and radially directed ventricular wall strain. Inter-study reproducibility is important for serial assessments however has not been defined for CMR-FT.

Methods

16 healthy volunteers were imaged 3 times within a single day. The first examination was performed at 0900 after fasting and was immediately followed by the second. The third, non-fasting scan, was performed at 1400.CMR-FT measures of segmental and global strain parameters were calculated. Left ventricular (LV) circumferential and radial strain were determined in the short axis orientation (Ecc_SAX and Err_SAX respectively). LV and right ventricular longitudinal strain and LV radial strain were determined from the 4-chamber orientation (Ell_LV, Ell_RV, and Err_LAX respectively). LV volumes and function were also analysed.Inter-study reproducibility and study sample sizes required to demonstrate 5% changes in absolute strain were determined by comparison of the first and second exams. The third exam was used to determine whether diurnal variation affected reproducibility.

Results

CMR-FT strain analysis inter-study reproducibility was variable. Global strain assessment was more reproducible than segmental analysis. Overall Ecc_SAX was the most reproducible measure of strain: coefficient of variation (CV) 38% and 20.3% and intraclass correlation coefficient (ICC) 0.68 (0.55-0.78) and 0.7 (0.32-0.89) for segmental and global analysis respectively. The least reproducible segmental measure was Ell_RV: CV 60% and ICC 0.56 (0.41-0.69) whilst the least reproducible global measure was Err_LAX: CV 33.3% and ICC 0.44 (0–0.77). Variable reproducibility was also reflected in the calculated sample sizes, which ranged from 11 (global Ecc_SAX) to 156 subjects (segmental Ell_RV). The reproducibility of LV volumes and function was excellent. There was no diurnal variation in global strain or LV volumetric measurements.

Conclusions

Inter-study reproducibility of CMR-FT varied between different parameters, as summarized above and was better for global rather than segmental analysis. It was not measurably affected by diurnal variation. CMR-FT may have potential for quantitative wall motion analysis with applications in patient management and clinical trials. However, inter-study reproducibility was relatively poor for segmental and long axis analyses of strain, which have yet to be validated, and may benefit from further development.