Cultured skin fibroblasts in schizophrenia: acute growth and susceptibility to damage

The study of cultured fibroblasts derived from skin biopsies of patients with inherited neurodegenerative disorders has aided in the elucidation of their pathological basis. This usefulness might be expected to extend to the study of fibroblast characteristics in schizophrenia in view of recent evidence of neurodegenerative changes in the disorder. In this study, the acute growth characteristics and response to toxic oxygen metabolites of fibroblast cell lines derived from skin biopsies of patients with schizophrenia (n = 9) are compared with those derived from psychiatric patients with various diagnoses not associated with a deteriorating course (controls = 11). No significant differences between the cell lines of the two patient groups are found.     

Exogastric neurilemmoma presenting as acute abdomen: Role of computed tomography in diagnosis

A case of subserosal gastric neurilemmoma is hereby presented. This reported case is unique in its clinical presentation including the appearance of acute abdomen and fever subsequent to unremarkable and uneventful upper gastrointestinal endoscopy. The tendency of neurilemmoma to cause mucosal ulceration with fistula formation probably led to this clinical presentation. The role of computed tomography in establishing diagnosis of exogastric tumor is emphasized.     

The contribution of a non-invasive test to clinical care. The impact of echocardiography on diagnosis, management and patient anxiety

We prospectively studied the impact of echocardiography on a cardiologist's diagnosis and management plan and on patient anxiety for 300 consecutive referrals. There was an impact on diagnosis in 90% of patients. Most common was confirmation of diagnosis usually with the addition of information pertinent to management (81%); change of disease category or resolution of diagnostic doubt was uncommon (9%). The consultant cardiologist believed the heart to be normal in 48 patients who did not have any associated disease; none had any echocardiographic abnormality. The cardiologist reported increased diagnostic confidence in 74% of all patients but management changed in only 9%. One-third of all patients reported reduced anxiety when this was an important clinical issue but in less than half of them did the cardiologist consider that echocardiographic information was essential for reassurance. Anxiety was increased in 6%, and in 12% the anxiety response was inconsistent with the test result. The clinical contribution of the test report was most obvious for those patients (30%) in whom this data was required for (a) a decision concerning specific diagnostic or technical intervention (b) a change of management plan which implied obvious or likely health benefit (c) reassurance which was a clinically important issue. The magnitude of this contribution was related to the study indication. The value of echocardiography is obvious when assessing patients for invasive intervention or when proper treatment or adequate reassurance are impeded by diagnostic doubt. However, for many current indications, we need better definition of factors which predict a clinically useful result. In particular, when the aim is to rule-out disease, our results suggest that an expert cardiological opinion would often be more appropriate than an echocardiogram.     

Translational crossroads for biomarkers.

A group of investigators met at a Specialized Programs of Research Excellence Workshop to discuss key issues in the translation of biomarker discovery to the development of useful laboratory tests for cancer care. Development and approval of several new markers and technologies have provided informative examples that include more specific markers for prostate cancer, more sensitive tests for ovarian cancer, more objective analysis of tissue architecture and an earlier indication of response to treatment in breast cancer. Although there is no clear paradigm for biomarker development, several principles are clear. Marker development should be driven by clinical needs, including early cancer detection, accurate pretreatment staging, and prediction of response to treatment, as well as monitoring disease progression and response to therapy. Development of a national repository that uses carefully preserved, well-annotated tissue specimens will facilitate new marker development. Reference standards will be an essential component of this process. Both hospital-based and commercial laboratories can play a role in developing biomarkers from discovery to test validation. Partnering of academe and industry should occur throughout the process of biomarker development. The National Cancer Institute is in a unique position to bring together academe, industry, and the Food and Drug Administration to (a) define clinical needs for biomarkers by tumor type, (b) establish analytic and clinical paradigms for biomarker development, (c) discuss ways in which markers from different companies might be evaluated in combination, (d) establish computational methods to combine data from multiple biomarkers, (e) share information regarding promising markers developed in National Cancer Institute-supported programs, and (f) exchange data regarding new platforms and techniques that can accelerate marker development.     

Comparison of scleral and corneal Tono-Pen readings.

PURPOSE: To compare scleral Tono-Pen (Medtronic Solan, Jacksonville, FL) readings to corneal Tono-Pen readings. METHODS: Intraocular pressure (IOP) was measured prospectively in 72 eyes of 37 adult patients and in 10 eyes of 5 children. Measurements were taken on the central cornea and on the sclera. Recorded measurements were within 5% confidence levels by Tono-Pen. RESULTS: Corneal IOP ranged from 10 to 28 mm Hg (mean +/- standard deviation, 17.0 +/- 3.8 mm Hg). Scleral measurements ranged from 4 to 99 mm Hg (40.4 +/- 23.0 mm Hg). Scleral measurements ranged from 11 mm Hg lower to 76 mm Hg higher than corneal measurements. CONCLUSIONS: Tono-Pen readings obtained from sclera are of no clinical value and should not be used to approximate corneal IOP.     

Allicin inhibits SDF-1alpha-induced T cell interactions with fibronectin and endothelial cells by down-regulating cytoskeleton rearrangement, Pyk-2 phosphorylation and VLA-4 expression

Allicin, a major ingredient of fresh garlic extract that is produced during the crushing of garlic cloves, exerts various beneficial biological effects, including a broad spectrum of antimicrobial activity, antihyperlipidaemic and antihypertensive effects. However, how allicin affects the immune system is less well known, and its effect on human T cells has never been studied. Here, we examined the in-vitro effects of allicin on the functioning of T cells related to their entry to inflamed extravascular sites. We found that allicin (20-100 microm) inhibits the SDF-1alpha (CXCL12)-induced T cell migration through fibronectin (FN), and that this inhibition is mediated by the down-regulation of (i) the reorganization of cortical actin and the subsequent T cell polarization, and (ii) T cell adhesion to FN. Moreover, allicin also inhibited T cell adhesion to endothelial cells and transendothelial migration. The mechanisms underlying these inhibitory effects of allicin are associated with its ability to down-regulate the phosphorylation of Pyk2, an intracellular member of the focal adhesion kinases, and to reduce the expression of the VCAM-1- and FN-specific alpha4beta1-integrin (VLA-4). The ability of allicin to down-regulate these chemokine-induced and VLA-4-mediated T cell functions explains its beneficial biological effects in processes where T cells play an important role and suggests that allicin may be used therapeutically with chronic inflammatory diseases.