Influence of genetic loading,obstetric complications and premorbid adjustment on brain morphology in schizophrenia: a MRI study

Cerebrospinal fluid (CSF) space enlargement in schizophrenia is a prominent finding. This study was initiated to examine the influence of genetic loading, obstetric complications and premorbid adjustment on the extent of this enlargement. The sample of this MRI study consisted of 40 schizophrenic patients, 24 psychiatric and 40 healthy family members from 10 uniaffected and 19 multiple affected families with schizophrenia, such as 27 control subjects from non-affected families. The ventricle-to-brain-ratio (VBR), and the areas of the third ventricle, sylvian fissure, temporal horn and interhemispheric fissure at the slice where these structures reached their maximum were examined relatively to the corresponding total brain areas. The sum of CSF areas was calculated as a parameter for global atrophy. From MANCOVA adjusted for intervening variables the right VBR and the sum of CSF areas revealed significant differences between diagnostic groups. For these areas schizophrenic patients showed an increase compared to control subjects and family members with psychiatric disorder. Genetic loading influenced the interhemispheric fissure, enlarged in multiple affected compared to uniaffected families, and the temporal horn asymmetry, which was right sided (right > left) in control subjects and multiple affected families, but inverted in uniaffected families. Neonatal obstetric complications influenced only the size of the VBR, while premorbid adjustment predicted various CSF areas. In conclusion, schizophrenic subjects from multiple and uniaffected families showed a global atrophy, which was most pronounced in the VBR. Genetic loading seems to have an impact on frontal regions as the interhemispheric fissure and on the temporal horn. Received: 14 February 2002 / Accepted: 17 February 2003 Correspondence to Peter Falkai, MD     

The association between chronic diseases and fatigue in the working population

OBJECTIVE: The aims of this study were to examine (a) whether employees with a chronic disease report more fatigue than employees without a chronic disease, (b) whether number or type of chronic disease is related to fatigue, and (c) whether differences in fatigue level in various types of chronic diseases are related to psychological distress. METHODS: Data were taken from 12,137 employees. Fatigue was measured with the Checklist Individual Strength (CIS). RESULTS: Employees with a chronic disease reported more fatigue (OR=2.9, 95% CI=2.7-3.2). Small differences were observed in the level of fatigue in various types of diseases. A strong linear association between the number of chronic diseases and fatigue was found. Psychological distress explained the higher level of fatigue in some chronic diseases (gastrointestinal diseases and migraine). CONCLUSIONS: Fatigue is more common in employees with a chronic disease. A strong association between number of chronic diseases and fatigue exists. Fatigue in employees with a chronic disease can partly be explained by psychological distress. Some chronic diseases show a stronger association between psychological distress and fatigue.     

A survival-based scoring-system for initial graft function following orthotopic liver transplantation

Initial graft function following orthotopic liver transplantation is a major determinant of postoperative survival and morbidity. Despite several efforts to provide scoring-systems for initial graft function, there is still a lack of a generally accepted classification scheme. The previously published systems assessed initial graft function based on the first postoperative days or weeks using liver-related laboratory parameters. It was shown that in most cases the scoring-systems did not correlate with patient survival. We intended to refine the definition of initial graft function in order to provide a survival based classification system. In a retrospective analysis of 761 patients following primary liver transplantation, a new scoring-system for early postoperative graft function was developed. Statistically significant differences in long term survival were calculated for ALAT, ASAT, bile production and prothrombin activity on days 1, 3, 7, 14. Points were then assigned according to the degree of survival: improved survival=1 point, poor survival=2 points. Patients were split into three groups corresponding to initially good, moderate and poor function. Applying this score, early and late patient survival rates and incidence of initial non-function were statistically significantly different. This was in contrast to the Gonzalez and the Ploeg-Maring classification scales, which are based on arbitrarily chosen cutoff levels. Retransplantation rates and postoperative morbidity were comparable both for the new and the older systems. We can conclude that the presented refined scoring-system for initial graft function provides a significant correlation to patient survival and initial non-function. We recommend the refined system for future studies.     

Simulation of artificial vision: I. Eccentric reading of isolated words,and perceptual learning

Simulations of artificial vision were performed to assess "minimum requirements for useful artificial vision". Retinal prostheses will be implanted at a fixed (and probably eccentric) location of the retina. To mimic this condition on normal observers, we projected stimuli of various sizes and content on a defined stabilised area of the visual field. In experiment 1, we asked subjects to read isolated 4-letter words presented at various degrees of pixelisation and at various eccentricities. Reading performance dropped abruptly when the number of pixels was reduced below a certain threshold. For central reading, a viewing area containing about 300 pixels was necessary for close to perfect reading (>90% correctly read words). At eccentricities beyond 10 degrees, close to perfect reading was never achieved even if more than 300 pixels were used. A control experiment using isolated letter recognition in the same conditions suggested that lower reading performance at high eccentricity was in part due to the "crowding effect". In experiment 2, we investigated whether the task of eccentric reading under such specific conditions could be improved by training. Two subjects, naive to this task, were trained to read pixelised 4-letter words presented at 15 degrees eccentricity. Reading performance of both subjects increased impressively throughout the experiment. Low initial reading scores (range 6%-23% correct) improved impressively (range 64%-85% correct) after about one month of training (about 1 h/day). Control tests demonstrated that the learning process consisted essentially in an adaptation to use an eccentric area of the retina for reading. These results indicate that functional retinal implants consisting of more than 300 stimulation contacts will be needed. They might successfully restore some reading abilities in blind patients, even if they have to be placed outside the foveal area. Reaching optimal performance may, however, require a significant adaptation process.     

Effect of extracorporal high hydrostatic pressure on tumor cell adherence and viability

In orthopedic surgery, reconstruction of bone segments afflicted with cancer is done in various ways, including devitalization of the bone or replacement of the bone by artificial bone constructs. To devitalize bone cells, extracorporal irradiation or autoclaving is used although both methods have substantial disadvantages. We now introduce the technique of extracorporal high hydrostatic pressure (HHP) treatment to disintegrate tumor cells in suspension or in their adherent state. The effect of HHP on cell viability, adherence and morphology of four different tumor cell lines (fibrosarcoma HT-1080, osteosarcoma SAOS-2, ovarian cancer OV-MZ-6, breast cancer MCF-7) was investigated. For this, adherently growing (with fibronectin serving as the growth-promoting substrate) or suspended tumor cells were placed into a test vial which was transferred into the pressure chamber of a high hydrostatic pressure device. After pressure treatment, the pressure was relaxed to atmospheric pressure and subsequently cell viability, adherence and morphology assessed. High hydrostatic pressure as high as 350 MPa (10 min, 37 degrees C) did not detach the tumor cells from the fibronectin-coated surface although at these conditions all of the four cell lines tested were irreversibly damaged. Adherently growing tumor cells were considerably more sensitive to HHP than tumor cells detached from the surface and treated by HHP in suspension. HHP-treated tumor cells showed drastic morphological changes, evident by cell membrane ruffling and bleb formation. At 150 MPa adherently growing or suspended tumor cells are irreversibly damaged by short-term treatment with HHP. In another investigation, we experienced that treatment of freshly excised bones or tendons by HHP has no adverse effect on their stability or biomechanical properties. Therefore, we anticipate that in orthopedic surgery HHP could be used as a new gentle way of treating resected cancer-afflicted bones or tendons to inactivate tumor cells before autologous reimplantation.     

Synthetic lipopeptide adjuvants and Toll-like receptor 2--structure-activity relationships

Bacterial lipoproteins and their synthetic analogues (sLP) are strong immune modulators of the early host responses after infection. Synthetic lipopeptides are strong adjuvants for the adaptive immune system. Lipoproteins and lipopeptides induce signalling in immune cells through Toll-like receptor-TLR2/TLR1 heterodimers. By screening a combinatorial lipohexapeptide amide collection in an in vitro IL-8 induction assay, we systematically evaluated the potential of 19 proteinogenic amino acids in the peptide moiety of Pam3Cys-lipopeptides to interact with TLR2. New Pam3Cys-lipopeptides with high activity were obtained. Different fatty acids were introduced to investigate the influence of the acyl moiety. Lipopeptides with modifications in the core structure of the unusual amino acid S-glycerylcysteine were synthesized and tested for IL-8 induction via TLR2.     

Technetium-99m mercaptoacetyltriglycine clearance: reference values for infants and children

Six hundred and thirty-nine clearance studies performed in children aged 7 days to 19 years utilizing technetium-99m mercaptoacetyltriglycine (MAG 3) were retrospectively analysed. Standardized conditions for the investigation included: parenteral hydration (60 ml/hxm² body surface) in addition to normal oral fluid intake, weight-related dose of^99mTc-MAG 3 (1 MBq/kg body weight, minimum 15 MBq) and calculation of clearance according to Bubeck et al. Of the 513 children, 169 included in this analysis could be classified as normal with regard to their renal function. Normal kidney function was judged by the following criteria: normal GFR for age, normal tubular function (absence of proteinuria and glucosuria), normal renal parenchyma (on ultrasonography, MAG 3 scan and intravenous pyelography), absence of significant obstruction and gross reflux (>grade 1), no single kidney and no difference in split renal function >20%. Results showed increasing MAG 3 clearance values for infants during the first months of life, reaching the normal range for older children and adults between 7 and 12 months.     

Cytosolic free [Ca2+] in mononuclear blood cells from demented patients and healthy controls

Summary There is increasing evidence that the neurodegenerative processes in Alzheimer's disease (AD) may be related to alterations in calcium homeostasis and that these metabolic changes are not necessarily restricted to the central nervous system. However, previous studies investigating [Ca²⁺]_i in fibroblasts, lymphoblasts, platelets and lymphocytes of AD patients gave inconclusive results, since increase, decrease and no alteration in [Ca²⁺]_i were found in AD patients compared with controls. With respect to the importance of establishing altered Ca²⁺ homeostasis in peripheral cells, we have investigated [Ca²⁺]_i in circulating mononuclear cells of patients with AD, multi-infarct dementia, age-associated memory impairment and healthy controls. [Ca²⁺]_i was evaluated using the fluorescent dye fura-2 before and during stimulation with phythaemagglutinin (PHA). In our study we failed to find major differences in resting [Ca²⁺]_i and in response to stimulation with 25g/ml and 100 g/ml PHA in cells of AD patients as compared with all other groups investigated. There was only a tendency towards a decrease in [Ca²⁺]_i in AD after stimulation with PHA. Thus the present findings suggest that [Ca²⁺]_i evaluation in mononuclear cells does not have diagnostic value in discriminating AD patients from other demented patients. However, there might be some difference in, [Ca²⁺]_i values between early- and late-onset AD, which could have pathophysiological importance.