Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research

Given the difficulty of procuring human brain tissue, a key question in molecular psychiatry concerns the extent to which epigenetic signatures measured in more accessible tissues such as blood can serve as a surrogate marker for the brain. Here, we aimed (1) to investigate the blood-brain correspondence of DNA methylation using a within-subject design and (2) to identify changes in DNA methylation of brain-related biological pathways in schizophrenia.We obtained paired blood and temporal lobe biopsy samples simultaneously from 12 epilepsy patients during neurosurgical treatment. Using the Infinium 450K methylation array we calculated similarity of blood and brain DNA methylation for each individual separately. We applied our findings by performing gene set enrichment analyses (GSEA) of peripheral blood DNA methylation data (Infinium 27K) of 111 schizophrenia patients and 122 healthy controls and included only Cytosine-phosphate-Guanine (CpG) sites that were significantly correlated across tissues.Only 7.9% of CpG sites showed a statistically significant, large correlation between blood and brain tissue, a proportion that although small was significantly greater than predicted by chance. GSEA analysis of schizophrenia data revealed altered methylation profiles in pathways related to precursor metabolites and signaling peptides.Our findings indicate that most DNA methylation markers in peripheral blood do not reliably predict brain DNA methylation status. However, a subset of peripheral data may proxy methylation status of brain tissue. Restricting the analysis to these markers can identify meaningful epigenetic differences in schizophrenia and potentially other brain disorders.Key words: DNA methylation, cross-tissue, blood, brain, correlation, schizophrenia     

Reproducibility and influence of hand rotation on computer-aided joint space analysis

ObjectivesComputer-aided joint space analysis (CAJSA) is a recently developed, semi-automated tool to aid in the measurement of joint space margins based on hand radiographs. The objective of this study is to verify the potential effect of hand rotation during X-ray imaging on the measurement of joint space width using CAJSA and to evaluate the reproducibility of the CAJSA technique in healthy subjects and in patients with rheumatoid arthritis.MethodsAll joint space distance (JSD) measurements were performed using CAJSA-technology at the metacarpophalangeal articulation based on conventional and digital hand radiographs.ResultsI. Hand rotation showed an effect on the reproducibility with CV ranging between 0.39% (angulation 1°) and 1.66% (angulation 19°). II. Regarding the overall reproducibility of the CAJSA method, the intra-radiograph reproducibility of JSD was calculated with CV = 0.54% for conventional images and CV = 0.38% for digital images. The inter-radiograph reproducibility error was observed with CV = 0.66% (conventional images) and CV = 0.63% (digital images). III. The study revealed a reproducibility for CAJSA measurements in RA ranging between 0.37% (JSD-MCP ring finger; van der Heijde-modification of the Sharp method Score 1) to 1.37% (JSD-MCP index finger; van der Heijde-modification of the Sharp method Score 3).ConclusionCAJSA measures JSD at the metacarpophalangeal articulation with high reproducibility in healthy subjects and in patients with differing stages of rheumatoid arthritis. Additional findings show that hand rotation during X-ray imaging has an impact on the CAJSA measurements; thus avoiding acquisition of hand radiographs with a rotation error of more than 15 degrees can be recommended.     

Traumatic subclavian arterial rupture: a case report and review of literature

ABSTRACT: Subclavian artery injuries represent an uncommon complication of blunt chest trauma, this structure being protected by subclavius muscle, the clavicle, the first rib, and the deep cervical fascia as well as the costo-coracoid ligament, a clavi-coraco-axillary fascia portion. Subclavian artery injury appears early after trauma, and arterial rupture may cause life-treatening haemorrages, pseudo-aneurysm formation and compression of brachial plexus. These clinical eveniences must be carefully worked out by accurate physical examination of the upper limb: skin color, temperature, sensation as well as radial pulse and hand motility represent the key points of physical examination in this setting. The presence of large hematomas and pulsatile palpable mass in supraclavicular region should raise the suspicion of serious vascular injury. Since the first reports of endovascular treatment for traumatic vascular injuries in the 90's, an increasing number of vascular lesions have been treated this way. We report a case of traumatic subclavian arterial rupture after blunt chest trauma due to a 4 meters fall, treated by endovascular stent grafting, providing a complete review of the past twenty years' literature.     

Spicae aetheroleum in uncomplicated acute bronchitis: a double-blind,randomised clinical trial

Wiener Medizinische Wochenschrift - The trial aimed to evaluate the efficacy and safety of Spicae aetheroleum (Spicae ae.), a phytomedicine obtained by steam distillation of the flowering...     

Near-infrared spectroscopic cerebral oxygenation reading in neonates and infants is associated with central venous oxygen saturation

BACKGROUND: The aim of the study was to elucidate easily determinable laboratory and vital parameters in clinical practice to explain variability of near-infrared spectroscopic cerebral oxygenation readings in critically ill newborns and infants using the NIRO 300 spectrometer. METHODS: Near-infrared spectroscopy (NIRS) cerebral tissue oxygenation index (cTOI) was measured on the forehead of critically ill neonates and infants with existing arterial and/or central venous access. We recorded patient characteristics and simultaneously determined sedation state, hemodynamic, respiratory and laboratory data, such as arterial blood gas analysis, electrolytes, hemoglobin and arterial lactate concentration, blood glucose and central venous oxygen saturation. Data were compared using linear, multiple and forward stepwise regression analysis (P < 0.05). RESULTS: A total of 155 neonates and infants aged from 0 to 365 days (median 12 days) were studied. cerebral tissue oxygenation index (cTOI) values ranged from 32.1 to 91.0% (60.5 +/- 11.5%). Simple linear regression analysis revealed significant associations between cTOI and arterial oxygen saturation (r = 0.254, P = 0.001), transcutaneously measured arterial oxygen saturation (r = 0.320, P < or = 0.0001), central venous oxygen saturation (r = 0.489, P < 0.0001), arteriovenous oxygen extraction (r = 0.445, P < 0.0001) and presence of a cardiac shunt (r = 0.250, P = 0.024). Multiple regression analysis and forward stepwise regression revealed two independent, significant predictors for cTOI, namely SvO2 (P < 0.0001) and presence or absence of a cardiac shunt (P = 0.003). SvO2 alone explained 23.9% of the variability of cTOI. The addition of the variable 'cardiac shunt' improved the model to 33%. CONCLUSIONS: Based on our study results cerebral tissue oxygenation readings by the NIRO 300 near-infrared spectrometer is influenced by central venous oxygen saturation, which partially explains intersubject variability of NIRS cerebral oxygenation readings.     

Glutamate infusion associated with reduced rises of p-Copeptin after coronary surgery: Substudy of GLUTAMICS II

Background

Glutamate plays a key role for post-ischaemic recovery of myocardial metabolism. According to post hoc analyses of the two GLUTAMICS trials, patients without diabetes benefit from glutamate with less myocardial dysfunction after coronary artery bypass surgery (CABG). Copeptin reflects activation of the Arginine Vasopressin system and is a reliable marker of heart failure but available studies in cardiac surgery are limited. We investigated whether glutamate infusion is associated with reduced postoperative rises of plasma Copeptin (p-Copeptin) after CABG.

Methods

A prespecified randomised double-blind substudy of GLUTAMICS II. Patients had left ventricular ejection fraction ≤0.30 or EuroSCORE II ≥3.0 and underwent CABG ± valve procedure. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h was commenced 10–20 min before the release of the aortic cross-clamp and then continued for another 150 min P-Copeptin was measured preoperatively and postoperatively on day one (POD1) and day three. The primary endpoint was an increase in p-Copeptin from the preoperative level to POD1. Postoperative stroke ≤24 h and mortality ≤30 days were safety outcomes.

Results

We included 181 patients of whom 48% had diabetes. The incidence of postoperative mortality ≤30 days (0% vs. 2.1%; p = .50) and stroke ≤24 h (0% vs. 3.2%; p = .25) did not differ between the glutamate group and controls. P-Copeptin increased postoperatively with the highest values recorded on POD1 without significant inter-group differences. Among patients without diabetes, p-Copeptin did not differ preoperatively but postoperative rise from preoperative level to POD1 was significantly reduced in the glutamate group (73 ± 66 vs. 115 ± 102 pmol/L; p = .02). P-Copeptin was significantly lower in the Glutamate group on POD1 (p = .02) and POD 3 (p = .02).

Conclusions

Glutamate did not reduce rises of p-Copeptin significantly after moderate to high-risk CABG. However, glutamate was associated with reduced rises of p-Copeptin among patients without diabetes. These results agree with previous observations suggesting that glutamate mitigates myocardial dysfunction after CABG in patients without diabetes. Given the exploratory nature of these findings, they need to be confirmed in future studies.     

Skeletonized bilateral internal mammary arteries for non-elective surgical revascularization in unstable angina.

OBJECTIVE: The aim of this study was to evaluate the feasibility, safety and outcome of skeletonized bilateral internal mammary arteries (BIMA) in patients with unstable angina (UA) undergoing non-elective myocardial revascularization. METHODS: Between January 1997 and December 2003, 758 patients, mean age 62+/-12 years, underwent non-elective coronary artery bypass grafting (CABG) for unstable angina. Two hundred and five (27%) were operated emergently and 503 (73%) urgently. BIMA were employed in 320 (42%) patients (Group B) and isolated left IMA and/or saphenous vein grafts in the remaining 438 (58%) patients (Group M). RESULTS: In-hospital mortality (B = 5.9% and M = 5.3%), and perioperative myocardial infarction (B = 2.2%; M = 1.96%) were similar between the two groups (P = ns). Actuarial survival at 1, 3 and 7 years was 98.7, 97.5 and 96.2% in B and 99, 94.3 and 88.4% in M (P < 0.05 at 7 years follow-up). At 7 years follow-up, the event-free cardiac survival (92 vs. 87%, P = 0.021), angina-free survival (98.6 vs. 94%, P = 0.039), reoperation-free cardiac survival (98 vs. 95%, P = 0.04) and infarct-free cardiac survival (98.7 vs. 96%, P = 0.05) were better in Group B. Multivariate analysis identified age > 65 years (P = 0.02), LVEF < 35% (P = 0.01), > 1 ischemic irreversible area (P = 0.03) as independent predictors for late deaths, while the use of the LIMA (P=0.006) and both mammary arteries (P=0.001) decreased the risk of late deaths. CONCLUSIONS: The use of BIMA in non-elective CABG for UA is safe and effective. Mid-term outcome, however, are superior with improved freedom from cardiac death, from coronary reintervention and from myocardial infarction.     

Endovascular repair for concomitant multilevel aortic disease.

OBJECTIVE: Patients with multilevel aortic disease represent a small subgroup with the need for extensive surgical treatment at considerable risk. We present our experience of endovascular exclusion for simultaneous thoracic and abdominal aortic disease in four patients. METHODS: Between January 2002 and January 2005, four patients underwent endovascular repair for simultaneous thoracic and abdominal aortic disease. Mean age was 69+/-10 years (range, 60-81). Thoracic lesions included penetrating aortic ulcer (n=2, ruptured=1), atherosclerotic aneurysm (n=1), and chronic type B dissection (n=1). Abdominal aortic disease included atherosclerotic infrarenal (n=3) and juxtarenal (n=1) aortic aneurysms. Thoracic aortic stent-grafts had been the following: Excluder/TAG (n=3) or Talent (n=1) straight tube devices. Abdominal aortic stent-grafts used were as following: Excluder (n=3) or Zenith (n=1). All patients were followed-up with CT-angiography and chest X-rays 1, 4, 12 months after the procedure, and once per year thereafter. RESULTS: Stent-graft deployment was technically successful in all cases. Intraoperative mortality was not observed. Mean procedure time was 94+/-34 min (range, 70-145). Early postoperative complications occurred in one patient that developed acute renal failure but dialysis was not required. Mean hospitalisation was 8+/-5 days (range, 4-15). Late death occurred in one patient for an undetected ruptured thoracic type 1 endoleak. All three survivors are currently well 16.5 months (range, 3-36) after surgery. No neurological complications developed. CONCLUSION: Simultaneous abdominal and thoracic endovascular repair for multilevel aortic disease is feasible and could be a viable alternative in high-risk patients, who otherwise may not be suitable candidates for conventional repair.     

A randomized trial comparing axillary dissection to no axillary dissection in older patients with T1N0 breast cancer: results after 5 years of follow-up

SUMMARY BACKGROUND DATA: Axillary dissection, an invasive procedure that may adversely affect quality of life, used to obtain prognostic information in breast cancer, is being supplanted by sentinel node biopsy. In older women with early breast cancer and no palpable axillary nodes, it may be safe to give no axillary treatment. We addressed this issue in a randomized trial comparing axillary dissection with no axillary dissection in older patients with T1N0 breast cancer. METHODS: From 1996 to 2000, 219 women, 65 to 80 years of age, with early breast cancer and clinically negative axillary nodes were randomized to conservative breast surgery with or without axillary dissection. Tamoxifen was prescribed to all patients for 5 years. The primary endpoints were axillary events in the no axillary dissection arm, comparison of overall mortality (by log rank test), breast cancer mortality, and breast events (by Gray test). RESULTS: Considering a follow-up of 60 months, there were no significant differences in overall or breast cancer mortality, or crude cumulative incidence of breast events, between the 2 groups. Only 2 patients in the no axillary dissection arm (8 and 40 months after surgery) developed overt axillary involvement during follow-up. CONCLUSIONS: Older patients with T1N0 breast cancer can be treated by conservative breast surgery and no axillary dissection without adversely affecting breast cancer mortality or overall survival. The very low cumulative incidence of axillary events suggests that even sentinel node biopsy is unnecessary in these patients. Axillary dissection should be reserved for the small proportion of patients who later develop overt axillary disease.