High-dose gadoteridol in MR imaging of intracranial neoplasms.

Twelve patients with a high suspicion of brain metastases by previous clinical or radiologic examinations were studied in a phase III investigation with magnetic resonance (MR) imaging at 1.5 T after a bolus intravenous injection of 0.1 mmol/kg gadoteridol followed at 30 minutes by a second bolus injection of 0.2 mmol/kg gadoteridol. All lesions were best demonstrated (showed greatest enhancement) at the 0.3-mmol/kg (cumulative) dose, with image analysis confirming signal intensity enhancement in the majority of cases after the second gadoteridol injection. More lesions were detected with the 0.3-mmol/kg dose than with the 0.1-mmol/kg dose, and more lesions were detected with the 0.1-mmol/kg dose than on precontrast images. In this limited clinical trial, high-dose gadoteridol injection (0.3-mmol/kg cumulative dose) provided improved lesion detection on MR images specifically in intracranial metastatic disease.     

Does too much urology damage your eyesight? Study of macular function.

A study comparing the macular function of both eyes of 130 urological surgeons was carried out to investigate whether the increased light exposure to the endoscoping eye caused any deterioration of macular function. The non-endoscoping eye was used as a control. A sophisticated computer test of colour contrast sensitivity was used. The computer assesses the degree of brightness at which the subject is just able to detect a coloured grating, and for each eye this is expressed as a threshold for the red/green axis and the blue/yellow (tritan) axis. The subjects also completed a questionnaire about their working patterns and their general and ophthalmic history and had a brief examination of the fundus. The results do not suggest that urologists are suffering any significant macular damage as a result of their work with endoscopes.     

Skeletal Functions of Vitamin K-Dependent Proteins: Not Just for Clotting Anymore

Osteocalcin and matrix Gla protein (MGP) are two vitamin K-dependent proteins present in bone and cartilage. Transgenic mice models were recently developed to isolate the function of each of these proteins. While osteocalcin-deficient mice have increased bone formation, MGP-deficient mice have abnormal calcification leading to osteopenia, fractures, and premature death owing to arterial calcification.     

Executive cognitive deficits in primary dystonia.

Primary dystonia is a disorder of movement for which no consistent pathophysiology has been identified; in the absence of evidence to the contrary, it is assumed to be cognitively benign. We have studied a clinically heterogeneous group of 14 patients with primary dystonia on a battery of neuropsychological tests. Despite well-preserved speed of information processing, language, spatial, memory and general intellectual skills relative to normal controls, we have identified a constellation of attentional-executive cognitive deficits on the Cambridge Neuropsychological Test Automated Battery (CANTAB). Specifically, patients demonstrated significant difficulties negotiating the extra-dimensional set-shifting phase of the IED task. The implications of these findings for the pathophysiology of primary dystonia are discussed. This is, to the best of our knowledge, the first report of a significant cognitive deficit in patients with primary dystonia.     

Opioid binding in DYT1 primary torsion dystonia: an 11C-diprenorphine PET study.

The opioid transmitters enkephalin and dynorphin are known to regulate pallidal output and consequently cortical excitability. Indeed, abnormal basal ganglia opioid transmission has been reported in several involuntary movement disorders, including levodopa-induced dyskinesias in Parkinson's disease (PD), tardive dyskinesias/dystonia, Huntington's disease, and Tourette's syndrome. Moreover, a previous 11C-diprenorphine PET study investigating levodopa-induced dyskinesias found reduced opioid receptor availability in PD with but not without dyskinesias. We wished to investigate if a similar alteration in basal ganglia opioid binding was present in DYT1 primary torsion dystonia (PTD). Regional cerebral 11C-diprenorphine binding was investigated in 7 manifesting carriers of the DYT1 gene and 15 age-matched normal controls using a region-of-interest (ROI) approach and statistical parametric mapping (SPM). No difference in regional mean 11C-diprenorphine binding was found between DYT1-PTD and controls, and no correlation between the severity of dystonia and opioid binding was seen. We conclude that aberrant opioid transmission is unlikely to be present in DYT1-PTD and altered opioid transmission is not a common mechanism underlying all disorders of involuntary movement.     

Integrating behavioral and social science into a public health agency: A case study of New York City

In the last century, both the health and life expectancy of Americans improved dramatically. These gains were primarily the result of advances in public health. But the approaches used may not be adequate to achieve the next level of improvements in health. Because health exists in the context of social, environmental, community, religious, political, and other spheres, ecological approaches that incorporate behavioral and social science theory and methodologies may provide the best avenue for advancing health in the 21st century. In 1999, the New York City Department of Health (NYCDOH) undertook the task of integrating behavioral and social science into its public health practice. The experience serves as a case study on the integration process at a public health agency.     

Anti-leukemia effect of perillyl alcohol in Bcr/Abl-transformed cells indirectly inhibits signaling through Mek in a Ras- and Raf-independent fashion.

PURPOSE: Perillyl alcohol (POH) displays preventive and therapeutic activity against a wide variety of tumor models, and it has been suggested that this might be associated with the ability of POH to interfere with Ras prenylation. POH also selectively induces G(1) arrest and apoptosis in Bcr/Abl-transformed hematopoietic cells. Because signaling through Ras is necessary for Bcr/Abl transformation, we examined whether POH induces its anti-leukemia effect by inhibiting Ras signaling. EXPERIMENTAL DESIGN: The ability of POH to inhibit posttranslational farnesylation and signaling from Ras as well as signaling through the Raf-Mek-Erk cascade was examined in Bcr/Abl-transformed and mock-transformed cells and related to the anti-leukemia effect of POH. RESULTS: POH does not affect Ras prenylation or Ras activity, but it blocks signaling downstream of Ras by reversing the state of activation of the Erk kinase, Mek. POH affects Mek activity only when it is added to intact cells. Treatment of either cell lysates or of purified Mek with POH has no effect on Mek activity. Inhibition of the Mek-Erk pathway seems to be related to the POH anti-leukemia effect for the following reasons: (a) the concentration of POH needed to block the Erk pathway, as well the kinetics with which POH inhibits this signaling cascade, both correlate with the anti-leukemia effect of POH; (b) both U0126 (a specific Mek inhibitor) and POH induce similar anti-leukemia effects; and (c) mock-transformed hematopoietic cells are simultaneously resistant to POH anti-leukemia effects and inhibition of the Mek-Erk pathway. CONCLUSION: Blocking Mek is sufficient to induce growth arrest and apoptosis in Bcr/Abl-transformed cells; therefore, POH represents a novel small molecule inhibitor of Mek that might be effective for treating Bcr/Abl leukemias.