Lithium-induced Clock Gene Expression in Lymphoblastoid Cells of Bipolar Affective Patients.

INTRODUCTION: Disturbances of circadian rhythms occur in all episodes of bipolar disorder (BD). Lithium, as gold-standard in the maintenance treatment of BD, is known to influence circadian processes. METHODS: In a pilot study lymphoblastoid cell lines (LCLs) were generated from 8 BD patients and 6 healthy controls. The LCLs were treated with lithiumchloride (LiCl) for 3 weeks. Cell cycles were then synchronized and expressional analysis by quantitative Real Time PCR was done. RESULTS: BD and controls differed in the period length regarding DBP (albumin D-box binding protein) expression and DBP expression was also influenced by lithium treatment. Furthermore, baseline DBP expression was significantly different between non-treated BD and healthy controls. None of the other analyzed circadian genes showed to be influenced by chronic lithium treatment or to be differentially regulated due to the diagnosis. DISCUSSION: We here show that chronic lithium treatment of LCLs leads to decreased expression of the clock gene DBP, rendering DBP a lithium-regulated gene. We could confirm the role of the circadian clock as well in lithium mode of action as in the pathomechanisms of BD although future studies with a greater number of participants and cell lines are needed.

Auto-masked 2D/3D image registration and its validation with clinical cone-beam computed tomography.

Image-guided alignment procedures in radiotherapy aim at minimizing discrepancies between the planned and the real patient setup. For that purpose, we developed a 2D/3D approach which rigidly registers a computed tomography (CT) with two x-rays by maximizing the agreement in pixel intensity between the x-rays and the corresponding reconstructed radiographs from the CT. Moreover, the algorithm selects regions of interest (masks) in the x-rays based on 3D segmentations from the pre-planning stage. For validation, orthogonal x-ray pairs from different viewing directions of 80 pelvic cone-beam CT (CBCT) raw data sets were used. The 2D/3D results were compared to corresponding standard 3D/3D CBCT-to-CT alignments. Outcome over 8400 2D/3D experiments showed that parametric errors in root mean square were <0.18° (rotations) and <0.73 mm (translations), respectively, using rank correlation as intensity metric. This corresponds to a mean target registration error, related to the voxels of the lesser pelvis, of <2 mm in 94.1% of the cases. From the results we conclude that 2D/3D registration based on sequentially acquired orthogonal x-rays of the pelvis is a viable alternative to CBCT-based approaches if rigid alignment on bony anatomy is sufficient, no volumetric intra-interventional data set is required and the expected error range fits the individual treatment prescription.

Clinical validation of a continuous non-invasive haemodynamic monitor (CNAP™ 500) during general anaesthesia.

BACKGROUND: We conducted a prospective study to test the validity of a new continuous non-invasive blood pressure (NIBP) monitor (CNAP) (CNAP™ Monitor 500). METHODS: One hundred patients undergoing elective surgery under general anaesthesia were included in the study after informed written consent. The CNAP finger cuffs were placed on the fingers of one arm, an arterial catheter was inserted into the same arm and data were recorded simultaneously. Agreement between invasive arterial pressure (IAP) and blood pressure obtained by CNAP was compared using the Bland-Altman method for repeated measurements. The data from the first 50 patients (software V3.0) were used to improve the software of the CNAP (software V3.5), which was then evaluated in another 50 patients. We defined a clinically acceptable agreement according to the standards of the American Association for the Advancement of Medical Instrumentation for NIBP measurements [limits of agreement (LOA) ± 15 mm Hg]. RESULTS: We analysed 524 878 paired measurements in 100 patients. The mean bias of the mean arterial pressure in the first 50 patients was -2.9 mm Hg (sd 10.6 mm Hg, LOA -23.7 to 17.9 mm Hg), and in the consecutive 50 patients (using software V3.5) the bias was -3.1 mm Hg (sd 9.5 mm Hg, LOA -21.6 to 15.4 mm Hg). CONCLUSIONS: The new CNAP monitor showed an agreement with the IAP that is promising but did not match our predefined criteria.

Health effects of sulfur-related environmental air pollution. III. Nonspecific respiratory defense capacities.

Recently concern has been raised about health effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on respiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to 1.0 microm neutral sulfite aerosol with a particle associated sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to 1.1 microm acidic sulfate aerosol providing an hydrogen ion concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each dog. A second group of eight dogs (control) was kept for the entire study under clean air conditions. Nonspecific defense mechanisms in the airways and in the peripheral lung were studied during chronic exposure of the combination of neutral sulfur(IV) and acidic sulfur(VI) aerosols. No functional changes of tracheal mucus velocity were found, in agreement with unchanged morphometry of the airways. However, the exposure resulted in changes of several alveolar macrophage (AM) mediated particle clearance mechanisms: (1) Based on in vivo clearance analysis and cultured AM studies using moderately soluble cobalt oxide particles, intracellular particle dissolution was significantly reduced since phagolysosomal proton concentration was decreased. We deduce exposure-related malfunction of proton pumps bound to the phagolysosomal membrane as a result of an increase of cytosolic proton concentration. (2) Based on in vivo clearance analysis using insoluble polystyrene particles, AM-mediated particle transport from the lung periphery toward ciliated terminal bronchioli and further to the larynx was significantly reduced. Activation of epithelial type II cells at the entrance of alveoli was inferred from observed type II cell proliferation at those alveolar ridges and enhanced secretion of alkaline phosphatase in the fluid of bronchoalveolar lavages. As a result, hypersecretion of chemotactic mediators by activated type II cells at these loci led to the observed decrease of particle transport toward ciliated bronchioli. (3) Based on in vivo clearance analysis using insoluble polystyrene particles, particle transport from the alveolar epithelium into interstitial tissues was increased and (4) particle transport to the tracheobronchial lymph nodes was significantly enhanced. Particle transport into interstitial tissues is the most prominent clearance pathway from the canine alveolar epithelium. We conclude that the deteriorated particle transport toward ciliated terminal bronchioli resulted in an enhanced particle transport across the epithelial membrane into interstitial tissues and the lymphatic drainage. The observed alterations in alveolar macrophage-mediated clearance mechanisms during chronic exposure of these air pollutants indicate an increased risk of health.

[Osteoplastic tooth transposition. Surgical method for orthognathic placement of a single tooth]. / Die osteoplastische Zahntransposition. Eine chirurgische Methode zur orthograden Einstellung von Einzelzähnen.

The procedure described in this article is based on the surgical subtotal luxation of a tooth-containing alveolar segment and allows the repositioning of single teeth while almost regularly safeguarding tooth vitality. This procedure has proven particularly effective in the treatment of maxillary anteriors, canines and premolars. For patients preferring surgical correction to long-term orthodontic treatment this limited operative intervention allows safe orthodontic alignment. To date, relapses have not been observed in the cases treated. Stable immobilization of up to six weeks postoperatively is achieved by splinting.