Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells.

Phospholipidosis (PLD) is characterized by an intracellular accumulation of phospholipids in lysosomes and the concurrent development of concentric lamellar bodies. Recently, H. Sawada et al. (2005, Toxicol. Sci. 83, 282-292) identified 17 genes as potential biomarkers of PLD in HepG2 cells. The present study was undertaken to determine if this set of genes measured by quantitative PCR could be validated in the same cell line. The objective was also to investigate the dose-response relationship to further validate the assay and to select the concentrations to use for screening activities. In a first experiment (one concentration tested), out of the 17 genes, the best gene biomarkers of PLD (i.e., 11 genes) were selected for practical screening reasons. Based on these genes, 91.6% (i.e., 11 of 12) of the compounds known to induce PLD were identified as positive and all the negative compounds (i.e., five of five) were also confirmed. When the data obtained in the first experiment were compared to the data by Sawada et al., (2005) the coefficient of correlation calculated was slightly higher than 75%. In the second experiment (26 compounds [all 17 compounds from the first experiment plus 9 other compounds] tested at a minimum of three concentrations), 93.3% (14/15) of the compounds known to induce PLD were identified as such and all the negative controls (six compounds) were also confirmed. Three compounds likely to induce PLD were identified as positive in our assay. Finally, two compounds for which no data are available were also tested. When both experiments 1 and 2 were compared, the coefficient of correlation for 16 compounds tested at the same concentrations reached 87.7%. In conclusion, the present study further confirms the utility of gene expression in HepG2 cells to identify a potential to induce PLD. Finally, based on the data presented, researchers are encouraged to use a range of minimum three concentrations (e.g., 12.5, 25, and 50 microM) to screen for PLD in the human HepG2 cell line.     

Digital movement analysis,a new objective method of measuring tardive dyskinesia and drug-induced parkinsonian tremor: acceptability,reliability and validity

Digital movment analysis (DMA) is a new instrumental approach to assessing oral tardive dyskinesia (TD) by means of digital image processing of a video signal, tracking five paper dots placed around the patient's mouth. A total of 40 schizophrenic patients, 30 with and 10 without TD, were examined twice (with a 3-month interval) with this new device. The patients were further examined with two TD rating scales: the St. Hans Rating Scale for extrapyramidal syndromes (SHRS) and the Abnormal Involuntary Movement Scale (AIMS).The schizophrenic patients accepted the instrumental assessment without any anxiety or resistance. The internal relibility of the apparatus was high, with correlation coefficients of 0.80–0.99. The DMA TD values correlated with the SHRS and AIMS scores with correlation coefficients of 0.48–0.73 indicating an acceptable, although not strong, concurrent validity. Fluctuations occurred from the first to the second examination independent of medication. For these fluctuations no correlation was found between DMA values and rating scores. Finally, the DMA device was able to detect perioral tremor as a sign of parkinsonism.It has been concluded that DMA is a useful supplement to classical TD rating, although further validity evaluation is warranted.     

Negative symptoms in schizophrenia: considerations for clinical trials

There is little agreement about the methodology of clinical trials of antipsychotic drugs in patients with negative symptoms. A literature review revealed wide variation in experimental design, rating scales and study duration. This reflects differing views as to the definition and response to treatment of negative symptoms. Some degree of standardization would improve comparability of studies and aid the development of new compounds. Patients included in such studies should have displayed negative symptoms for at least 6 months. Depressive symptoms, positive schizophrenic symptoms and extrapyramidal signs may all influence or be confused with negative symptoms and may respond to treatment; they should be at a low level at baseline and should be measured during the study period. Studies should last at least 8 weeks. Several scales are available for measuring negative symptoms and are reviewed; a global impression score should be used additionally.     

Peritoneal morphology in children treated by continuous ambulatory peritoneal dialysis

Fifty peritoneal biopsies (PB) from 35 patients with end-stage renal disease, treated by continuous ambulatory peritoneal dialysis (CAPD) and aged 2 months to 18 years, were examined by light microscopy (n=50) and/or scanning electron microscopy. PB were performed during surgical procedures immediately before the start of, during, or after the cessation of CAPD treatment. PB from 15 children without renal disease undergoing laparatomy were examined similarly. Before the start of CAPD, a scarcity and shortening of the mesothelial microvilli was observed by scanning electron microscopy. During and after CAPD, variable alterations of mesothelium, interstitium and capillaries were found. The mesothelial layer was absent in all 5 PB obtained during episodes of active peritonitis. In patients treated by CAPD for longer than 6 months, mesothelial denudation was observed more frequently (6/11) than in children treated for shorter periods (1/7) (P<0.08). Fibrosis of the peritoneal membrane was present in about 50% of patients during or after the cessation of CAPD without impairment of peritoneal function. No correlation was found between the presence of fibrosis and the frequency of peritonitis or the duration of CAPD treatment.     

Morphological changes in chest radiographs of patients with acute respiratory distress syndrome (ARDS)

Objective: To determine whether the quality of infiltrations in chest radiographs can accurately predict the histological extent of fibrotic change in patients with acute respiratory distress syndrome (ARDS). Design: Retrospective clinical investigation. Setting: Intensive care unit (ICU) of a university teaching hospital. Patients and methods: Of 47 patients treated with extracorporeal membrane oxygenation (ECMO) for severe ARDS over a 5-year period, 23 patients underwent open lung biopsy at thoracotomy for treatment, mostly of pneumothorax. Chest films obtained by portable chest roentgenography preceding the operation were reviewed retrospectively and compared to the histomorphological results of the lung specimen. Results: Chest radiographs displayed mixed alveolar-reticular opacification in 60.2 %, alveolar patterns in 22.9 % and reticular opacities in 10.5 %. In 0.4 % there were no infiltrates, 6 % could not be evaluated because of insufficient quality. There was no relevant difference between the right and left lungs. Subdividing patients into two groups according to the histological results of either absent or mild (1) or severe (2) lung fibrosis, we found an alveolar haziness in 12.3 % in group 1 compared with 28.2 % in group 2, while reticular characteristics were identified in 13 % and 11 %, respectively. Conclusions: The most common opacity in chest radiographs of patients with severe ARDS treated with ECMO is mixed alveolar-reticular opacification. Severe lung fibrosis is not positively correlated with a reticular radiographic pattern. ECMO does not lead to specific radiological changes in conventional radiograms, contrary to clinical findings that treatment with ECMO might induce pleural or pulmonic haemorrhage, especially in the earlier days when systemic heparinization had to be used instead of the heparin-coated tube-surfacing. Received: 24 November 1997 Accepted: 20 July 1998     

The Mother-Observer Relationship: An Examination of the Participant Role of the Observer in Mother-Infant Observation

SUMMARY. The relationship between mother and observer in mother-infant observation as described by Esther Bick is examined. Specifically, the question as to whether this relationship influences what is being observed is considered.
The author gives an account of her own relationship as an observer with a mother. The mother was an epileptic and fell with her baby (then six weeks old) causing the baby to suffer a broken skull. Exploration of events during the period of observation leads to the conclusion that the relationship between the mother and the observer was one of transference. Within this transference the observer seemed to be the mother of the one observed. This together with the effects on the observed mother's unconscious conflict with her own mother due to epilepsy is described.
Given transference in the mother-observer relationship doubts are raised as to the tenability of the attitude of distance and non-interference prescribed for the observer. The conclusion is drawn that, in any case, the role of the observer is a participant role, which poses the epistemological problem of the interference of the observer with the observed.