Individual differences in psychotic effects of ketamine are predicted by brain function measured under placebo

The symptoms of major psychotic illness are diverse and vary widely across individuals. Furthermore, the prepsychotic phase is indistinct, providing little indication of the precise pattern of symptoms that may subsequently emerge. Likewise, although in some individuals who have affected family members the occurrence of disease may be predicted, the specific symptom profile may not. An important question, therefore, is whether predictive physiological markers of symptom expression can be identified. We conducted a placebo-controlled, within-subjects study in healthy individuals to investigate whether individual variability in baseline physiology, as assessed using functional magnetic resonance imaging, predicted psychosis elicited by the psychotomimetic drug ketamine and whether physiological change under drug reproduced those reported in patients. Here we show that brain responses to cognitive task demands under placebo predict the expression of psychotic phenomena after drug administration. Frontothalamic responses to a working memory task were associated with the tendency of subjects to experience negative symptoms under ketamine. Bilateral frontal responses to an attention task were also predictive of negative symptoms. Frontotemporal activations during language processing tasks were predictive of thought disorder and auditory illusory experiences. A subpsychotic dose of ketamine administered during a second scanning session resulted in increased basal ganglia and thalamic activation during the working memory task, paralleling previous reports in patients with schizophrenia. These results demonstrate precise and predictive brain markers for individual profiles of vulnerability to drug-induced psychosis.     

Electrophysiological properties of neurons in neonatal rat occipital cortex slices grown in a serum-free medium

The electrophysiological properties of individual neurons within organotypic explants of neonatal rat cortex were examined via intracellular recordings. The explants were grown for two weeks in a serum-free medium. The electrophysiological properties of the neurons within these explants were similar to those reported for both adult cortex in vivo and short-term in vitro slice preparations. The results of the present study show that cortical explants grown under serum-free conditions can serve as a useful model for long-term developmental studies associated with the physiological basis of neural network formation.     

Histopathological changes associated with high intensity focused ultrasound (HIFU) treatment for localised adenocarcinoma of the prostate

AIMS: Investigation of the histopathological changes in prostatectomy specimens of patients with prostate cancer after high intensity focused ultrasound (HIFU) and identification of immunohistochemical markers for tissue damage after HIFU treatment. METHODS: Nine patients diagnosed with adenocarcinoma of the prostate underwent unilateral HIFU treatment seven to 12 days before radical prostatectomy. The prostatectomy specimens were analysed histologically. Immunohistochemical staining and electron microscopy were performed to characterise more subtle phenotypic changes. RESULTS: All prostatectomy specimens revealed well circumscribed HIFU lesions at the dorsal side of the prostate lobe treated. Most epithelial glands in the centre of the HIFU lesions revealed signs of necrosis. Glands without apparently necrotic features were also situated in the HIFU lesions, raising the question of whether lethal destruction had occurred. This epithelium reacted with antibodies to pancytokeratin, prostate specific antigen (PSA), and Ki67, but did not express cytokeratin 8, which is indicative of severe cellular damage. Ultrastructural examination revealed disintegration of cellular membranes and cytoplasmic organelles consistent with cell necrosis. HIFU treatment was incomplete at the ventral, lateral, and dorsal sides of the prostate lobe treated. CONCLUSIONS: HIFU treatment induces a spectrum of morphological changes ranging from apparent light microscopic necrosis to more subtle ultrastructural cell damage. All HIFU lesions are marked by loss of cytokeratin 8. HIFU does not affect the whole area treated, leaving vital tissue at the ventral, lateral, and dorsal sides of the prostate.     

The effects of caffeine on visual selective attention to color: an ERP study

Event-related potentials were recorded from 11 subjects after ingesting caffeine (250 mg) or placebo. Subjects were instructed to attend selectively to stimuli with a specified color (red or blue) in order to react to the occurrence of a target within the attended category. Reaction times revealed faster responses for the caffeine condition, whereas no differences in strategy were observed. Color attention effects were identified as frontal selection positivity, occipital selection negativity, and N2b, whereas target detection was reflected in P3b. Effects of treatment were found as a more positive-going frontal P2 component in the caffeine condition. In addition, an interaction between attention and treatment could be observed on the N2b component. This pattern of results suggests that caffeine yields a higher overall arousal level, more profound processing of both attended and unattended information, and an acceleration of motor processes.     

Oblique lateral cephalometric radiographs of the mandible in implantology: usefulness and reproducibility of the technique in quantitative densitometric measurements of the mandible in vivo

In the literature intraoral periapical radiographs are commonly used for densitometric measurements of the mandible with implants. These films give detailed information of the implant and the surrounding bone. However, in extreme mandibular atrophy it can be difficult to obtain intraoral radiographs of adequate diagnostic quality. Extraoral Oblique Lateral Cephalometric Radiographs (OLCRs) can then be the alternative: reproducible images of large parts of the mandible can be obtained. In vitro, the results of densitometry using periapical films and OLCRs were shown to be similar. The present study aims to determine the measurement error of densitometry with OLCRs in vivo. In 16 patients (group I) with atrophic mandible and implants, duplicate OLCRs of one side of the jaw were obtained. The error of measurement for the densitometric measurements of the mandibular bone was 5.5%. The use of a specially developed correction program to compensate for undesired variations in the projection of the soft tissues of the face (tongue, lips, cheek and neck) on the radiographs resulted in a 40% reduction of that measurement error to 3.5%. This remaining error is mainly brought about by an imperfect repositioning of the patient when the duplicate OLCRs are obtained. The error caused by the image acquisition, processing and measurement is less than 1%. Deliberate variation up to 7.5 degrees of the horizontal angle wherein the OLCRs are made, results in a large error of measurement of 13.5% (group II: 17 patients). To reduce this variation the additional soft tissue correction program is unsuitable. It is concluded from this study that the described radiographic and image analysis technique is a promising tool for prospective densitometric studies of the mandible with or without implants. Especially in mandibles with bone grafts and implants, substantial changes in the graft can occur. The described technique may be particularly valuable in analyzing these changes.     

Stereological measurement of porto-central gradients in gene expression in mouse liver

The liver is thought to consist of lobules, numerous repeating, randomly oriented units. Within these lobules, genes are expressed in gradients along the porto-central axis, which spans the distance between portal and central veins. We have developed a robust stereological method to map all points in an image to their position on this porto-central axis. This approach is based on the distribution of well-characterized periportal and pericentral enzymes, which are visualized on sections preceding and following the section of interest. Because expression of the model genes phosphoenolpyruvate carboxykinase and ornithine aminotransferase declines gradually with increasing distance from the portal vein and central vein, respectively, these genes can be used to prepare images with topographical information without any assumption about the shape of the hepatic unit, or about the direction or shape of the gradient to be determined. The "relative distance" image is a 2-dimensional image that accurately maps the relative position of hepatocytes on the porto-central axis in 3-dimensional space. It is superimposed on the serial section under investigation to relate local staining density to position on the porto-central axis and obtain the gene expression gradient. The method was used to determine the expression gradient of 2 periportal and 2 pericentral enzymes and their response to fasting. The "total distance" image was used to measure the length of the porto-central axis, which was approximately 210 microm in mice and found to decrease 13% after 1 day of starvation. The method can be applied to any tissue component that can be stained quantitatively.     

Submucosal lipoma of the colon: abdominal cramps with rectal bleeding and weight loss

An 81-year-old woman had abdominal cramps, rectal bleeding since 2 weeks and weight loss. Colonoscopy showed an ulcerating tumour of about 4 cm in the transverse colon. Pathological examination of biopsies taken during colonoscopy indicated moderately active chronic colitis. Based on the colonoscopy findings, the tumour appeared to be malignant and laparotomy was performed and the transverse colon was resected. Pathological examination of the resected lesion revealed a submucosal lipoma. The patient recovered fully. Lipomas account for 4% of benign gastrointestinal tumours and 90% of lipomas are submucosal. Their presentation is often similar to malignant tumours. The naked fat sign after biopsy and the elasticity of the lesion are typical features encountered during colonoscopy. Given the high fat content of these lesions, they are easily discernible with CT and MRI. Lipomas with a diameter < 2 cm can be safely removed endoscopically. Larger lesions should be removed by segment resection.