Regional cerebral blood flow changes in schizophrenic patients detected by SPECT studies under resting and active conditions]

Brain SPECT studies in schizophrenia revealed changes in regional cerebral blood flow (rCBF). The rCBF changes can be detected more accurate by activating tests. The aim of this study was to assess rCBF changes under resting and activation condition by the Raven test. Four control patients (2 male, 2 female, average age 45 years, 26-57 years) and 11 chronic, treated schizophrenic patients (4 male, 7 female, average age: 46 years, 33-56 years) were studied in two HMPAO brain SPECT sessions, 48 hours apart, both resting and during activation task. The images were evaluated visually and semiquantitatively. Under resting condition in the control group, there were no significant rCBF changes. In the Raven activation test, a significantly higher blood flow in the prefrontal region was seen (p < 0.05). The schizophrenic group had a significantly lower rCBF in the temporal region under resting condition (p < 0.05): four patients displayed left, 4 right temporal hypoperfusion and 3 exhibited no rCBF abnormality. In the Raven activation tests 5 patients had prefrontal hyperperfusion, and the remaining 6 patients had no such activation answer. Five patients had hypoperfusion in the temporal region. In our sample, patients with chronic schizophrenia displayed significant temporal hypoperfusion. Moreover the chronic schizophrenic group exhibited a poor response to prefrontal activation compared to the control group.     

Contrast enhanced MRA of peripheral arteries with the automatic "floating table".

Magnetic resonance angiography (MRA) is increasingly used as a non-invasive alternative to digital subtraction angiography (DSA). Besides plain time-of-flight (TOF) and phase contrast (PC) MRA a new MRA technique using positive contrast agent has been introduced recently. A fast 3D gradient-echo sequence is applied to reach a significant reduction of measurement time for acquisition of the MRA within the first pass of the contrast agent, thereby avoiding venous overlap. A significant progress was yielded by MR systems allowing manual table movement for examination of the pelvis and the lower limbs in one examination with a single contrast agent bolus. However, in this case it is necessary to have a coworker in the examination room moving the table manually. In this paper we report a prototype system which allows automatic table movement ("floating table"). Using this novel system we examined a patient with an aneurysm of the abdominal aorta and peripheral arterial occlusive disease (PAOD). Diagnostic results of contrast enhanced MRA and DSA were equivalent. In summary, the automatic floating table system introduced in this paper allows comfortable non-invasive examination of pelvic and lower limb arteries. The value of this technique in comparison to DSA has to be determined in future studies.     

The influence of external sodium and potassium on lithium uptake by primary brain cell cultures at ‘therapeutic’ lithium concentration

The ionic regulating of lithium homeostasis and steady-state intra: extracellular lithium distribution in the brain can be approached by experimental methods using intact nerve cells in vitro. Primary cultures prepared from chick embryonic brain were applied to study the effect of extracellular sodium and potassium on the lithium uptake of nerve cells at therapeutic lithium concentration (1.5 mM). Lithium influx and the level of steady-state intracellular lithium were significantly reduced by increasing the external sodium concentration. At physiological extracellular sodium level, the steady-state content of lithium in the brain cells was about half of that observed in the presence of 10 mM sodium in the incubation media and the value of the intra: extracellular lithium distribution ratio was below 1. External potassium (0.5–3 mM) strongly inhibited lithium uptake of the nerve cells. Ouabain (10^-4 M) had no effect on this potassiumsensitive lithium uptake in Tyrode media. Sodium influx studied by isotope tracer methodology was higher in cultures preloaded with lithium as compared to that of the controls. It can be concluded that sodium and potassium ions, at physiological concentrations, significantly influence lithium uptake as well as the intra: extracellular lithium distribution in brain cell cultures.     

Nonsteroidal anti-inflammatory drug use associated with reduced incidence of adenocarcinomas of the esophagus and gastric cardia that overexpress cyclin D1: a population-based study.

This study was undertaken to determine whether selected risk factors for esophageal and gastric cancer are associated with tumors that overexpress cyclin D1. Archived tumor tissue was available for 630 esophageal and gastric cancer patients who participated in a population-based case-control study. Patients were categorized into case groups based on whether protein overexpression of the cyclin D1 gene, as assessed by immunohistochemistry, was present (cyclin D1+, n = 285) or not (cyclin D1-, n = 345) in the tumor. The distribution of risk factors in each of these case groups was then compared with the distribution among the 695 controls. Multivariate-adjusted odds ratios (OR) for esophageal adenocarcinoma were reduced in relation to use of aspirin and other nonsteroidal anti-inflammatory drug (NSAID) use but only among patients with cyclin D1+ tumors (0.45, 95% confidence interval [CI] = 0.26, 0.79) and not among those with cyclin D1- tumors (1.12, 95% CI = 0.67, 1.86). A similar pattern was observed for gastric cardia adenocarcinomas. In contrast, ORs for esophageal squamous cell carcinoma and noncardia gastric adenocarcinomas in relation to NSAID use were reduced, regardless of cyclin D1 status. ORs did not vary with cyclin D1 status in relation to alcohol, body size, or cigarette smoking, with the following exception; for noncardia gastric adenocarcinomas the cyclin D1- tumors showed a 2-fold elevation in the OR with ever smoking. These data suggest that the reduction in risk associated with NSAID use may be restricted to those esophageal and gastric cardia adenocarcinomas that overexpress cyclin D1.     

Characteristic expression profiles induced by genotoxic carcinogens in rat liver.

When applied in toxicological studies, the recently developed gene expression profiling techniques using microarrays, which brought forth the new field of toxicogenomics, facilitate the interpretation of a toxic compound's mechanism of action. In this study, we investigated whether genotoxic carcinogens at doses known to induce liver tumors in the 2-year rat bioassay deregulate a common set of genes in a short-term in vivo study and, if so, whether these deregulated genes represent defined biological pathways. Rats were dosed with the four genotoxic hepatocarcinogens dimethylnitrosamine (4 mg/kg/day), 2-nitrofluorene (44 mg/kg/day), aflatoxin B1 (0.24 mg/kg/day), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 20 mg/kg/day). After treatment for up to 14 days, the expression profiles of the livers were analyzed on Affymetrix RG_U34A microarrays. Among the significantly upregulated genes were a set of target genes of the tumor suppressor protein p53, indicating a DNA damage response. Such a response was expected and, therefore, confirmed the validity of our approach. In addition, the gene expression changes suggest a specific detoxification response, the activation of proliferative and survival signaling pathways, and some cell structural changes. These responses were strong throughout the 14 day time course for 2-nitrofluorene and aflatoxin B1; in the case of dimethylnitrosamine and NNK, the effects were weakly detectable at day 1 and then increased with time. For dimethylnitrosamine and aflatoxin B1, which caused observable inflammation in vivo, we found a corresponding upregulation of inflammatory genes at the same time points. Thus, by the toxicogenomic analysis of short-term in vivo studies, we identified genes and pathways commonly deregulated by genotoxic carcinogens, which may be indicative for the early events in tumorigenesis and, thus, predictive of later tumor development.     

Tracing Staphylococcus aureus in small and medium-sized food-processing factories on the basis of molecular sub-species typing

Contamination by Staphylococcus aureus of the production environment of three small or medium-sized food-processing factories in Slovakia was investigated on the basis of sub-species molecular identification by multiple locus variable number of tandem repeats analysis (MLVA). On the basis of MLVA profiling, bacterial isolates were assigned to 31 groups. Data from repeated samplings over a period of 3 years facilitated to draw spatial and temporal maps of the contamination routes for individual factories, as well as identification of potential persistent strains. Information obtained by MLVA typing allowed to identify sources and routes of contamination and, subsequently, will allow to optimize the technical and sanitation measures to ensure hygiene.