Assessment of brain tumor angiogenesis inhibitors using perfusion magnetic resonance imaging: quality and analysis results of a phase I trial

PURPOSE: To determine thresholds of quality for a T2*-weighted perfusion magnetic resonance imaging (MRI) study and evaluate the effects of an angiogenesis inhibitor on relative blood flow and volume changes in brain tumor patients in a multi-institution setting. MATERIALS AND METHODS: A total of 36 volunteers from four participating institutions with clinically diagnosed malignant gliomas were studied using perfusion MRI protocols. These included a baseline study and follow-up studies every eight weeks to evaluate the effect of an anti-angiogenic agent on tumor perfusion. Quality tests were performed on the perfusion imaging data by defining statistical thresholds of acceptance. Region of interest (ROI) analysis was performed on tumors and kinetic parameters were normalized with respect to normal tissue. RESULTS: Statistical thresholds for goodness of the gamma variate fit, T2* recovery, and mean signal full-width half-minimum (FWHMin) were computed for our data sets with a 99% one-sided confidence interval; these were 6.91%, 79.48%, and 23.35 seconds, respectively. Decreases in-blood volume and flow measurements were observed in patients with documented clinical response. CONCLUSION: Malignant brain tumors have altered perfusion parameters that may be used to understand and monitor neovascularization. This permits non-invasive assessment of the efficacy of angiogenesis inhibiting drugs.     

Carbamoylcholine homologs: synthesis and pharmacology at nicotinic acetylcholine receptors

In a recent study, racemic 3-(N,N-dimethylamino)butyl-N,N-dimethylcarbamate (1) was shown to be a potent agonist at neuronal nicotinic acetylcholine receptors with a high selectivity for nicotinic over muscarinic acetylcholine receptors [Mol. Pharmacol. 64 (2003) 865-875]. Here we present the synthesis and pharmacological characterization of a series of analogs of, where the methyl group at C-3 has been replaced by different alkyl substituents. Ring systems have been incorporated into the carbon backbone of some of the molecules, or the amino group has been build into ring systems. Furthermore, the (+)- and (-)-enantiomers of have been separated, and X-ray crystallography has revealed that (-)-1 possesses (S)-configuration. The compounds have been characterized pharmacologically at recombinant nicotinic receptor subtypes. The structure-activity relationship study has provided valuable insight into the mode of interactions of and its analogs with neuronal nicotinic acetylcholine receptors.     

Effects of firm size on risks and reporting of elevation fall injury in construction trades

Although many occupational safety programs are targeted toward large firms, the construction industry is dominated by smaller firms. This study examines the differential effect of firm size on the risk and the reporting of over 3000 serious and minor nonfatal elevation fall injuries in Danish construction industry trades (1993 to 1999). Small firms (<20 employees) accounted for 93% of all firms and 55% of worker-years. There was an inverse relationship between firm size and serious injury rates and a direct relationship between firm size and minor injury rates. An inverse relationship between firm size and injury severity odds ratios (serious versus minor) was found for carpentry, electrical work, general contracting, and the remaining other trades. Health and safety issues, legislation, and enforcement in the construction industry should, to a greater degree, be focused on smaller firms.     

Concordance of information in parallel electronic and paper based patient records

OBJECTIVE: to evaluate the results of parallel use of both paper based and electronic patient records with respect to concordance of corresponding information in two continuously updated versions of the same records. DESIGN: retrospective evaluation of patient records, comparing documentation in electronic and paper based patient records. SETTING: Department of Neurology in a Norwegian university hospital using paper based and electronic patient records in parallel during migration towards completely electronic patient records. MATERIAL: electronic and paper based patient records of 90 randomly selected patients visiting the department between 1 November 1997 and 30 April 1999. RESULTS: seven percent of the electronic documents were significantly different in some way from the corresponding paper documents. About 4-13% of the documents in the electronic record were missing; one percent were missing from the paper record. CONCLUSION: parallel use of electronic and paper based patient records has resulted in inconsistencies between the record systems in our setting. Documentation is missing in both the electronic and paperbased records. When implementing electronic record systems intended to operate in parallel with paperbased systems, focus should be on securing the validity of all versions of the record.     

Effect of intravenous magnesium on pain and secondary hyperalgesia associated with the heat/capsaicin sensitization model in healthy volunteers

We investigated the effects of i.v. magnesium on secondary hyperalgesiafollowing heat/capsaicin stimulation in human volunteers. Twenty-fivevolunteers were included in this double blind, randomized, crossoverstudy. Sensitization was induced in the volunteers, who werethen subjected to either i.v. saline or magnesium sulphate.No analgesic or antihyperalgesic effect could be demonstratedin sensitized skin during infusion of magnesium. In contrast,painfulness of thermal stimulation was increased in normal skin.These results suggest that i.v. magnesium has no important analgesiceffects in clinically relevant doses. Br J Anaesth 2001; 86: 871–3     

Do parents utilize physician follow-up after death of their newborn?

Numerous authors have advocated appropriate physician-patient counseling following a perinatal death. We examined, in a prospective manner, how many families utilized physician follow-up when such follow-up was offered. Seventy-six percent of the 108 families who experienced a neonatal death chose to have physician follow-up in the weeks after the death. A family's utilization of subsequent physician contact was not related to the distance they lived from the medical center, the duration of survival of the infant, or the racial background of the mother. Parents utilized follow-up visits whether or not an autopsy was performed or an interpreter was needed. Certain features distinguished the parents who did not utilize the physician follow-up service: parents were less likely to utilize the service if they were not married, the mother was a teenager, the head of the household was unemployed, or there was no phone at home.     

Effects of 5-hydroxytryptamine and ergotamine on human superficial temporal artery

Isometric tension was recorded in ring preparations of human superficial temporal arteries contracted by noradrenaline (NA), 5-hydroxytryptamine (5-HT), and ergotamine. In contrast to NA and 5-HT, ergotamine induced long-lasting contractions refractive to additional stimulations and resistant to repeated wash-out. When tested against 5-HT, ergotamine acted as a non-competitive antagonist. When repeating the 5-HT stimulations (4.7 × 10-5 M) the contractile response decreased indicating tachyphylaxis to this agent. As ergotamine revealed both a vasoconstrictive and a 5- HT-blocking activity, the beneficial effect in migraine may be by an interference during both the vasoconstrictory and vasodilatory phases.