Automated assay of vitamin B-12 by the Abbott IMx analyzer.

A nonisotopic assay of vitamin B-12 in human serum or plasma is described, performed with the Abbott IMx analyzer. The sample is first treated at pH > 12.5 to release bound vitamin B-12 and to convert all forms to cyanocobalamin. Next, the analyte is bound, at lower pH, by vitamin B-12-specific binding protein, immobilized to a solid phase of polymeric microspheres. Detection involves monitoring the activity of the tracer enzyme (alkaline phosphatase) coupled to a derivative of cyanocobalamin. Total assay precision is 7.9% for vitamin B-12 at 200 ng/L, 6.6% at 400 ng/L, and 6.7% at 800 ng/L. Assay sensitivity, calculated as 2 SD from the zero calibrator, is 37 (+/- 9) ng/L. The dynamic range extends to 2000 ng/L. Analytical recovery of 300 and 600 ng/L additions of vitamin B-12 to sera with basal concentrations of 30-400 ng/L was 102.5%. Results of the assay correlated well with those of commercially available radioisotope assays. No interference was observed in specimens from patients with pernicious anemia, chronic or acute myelogenous leukemia, or renal failure. Cross-reactivity with cobinamide (1 g/L) was < 0.00003%. Vitamin B-12 measurements for blood specimens drawn into serum, EDTA, or heparinized plasma-collection tubes agreed within 3%.     

A mechanically detachable coil for the treatment of aneurysms and occlusion of blood vessels.

PURPOSETo evaluate mechanically detachable coil designs capable of controlled and instantaneous release within an aneurysm or vascular space.METHODSThree mechanically detachable coil designs, clamped ball, looped ribbon, and interlocking cylinder, were evaluated using in vitro and in vivo testing to study reliability of coil release, retractability, and coil behavior in a microcatheters. In vitro tests were performed using a glass side-wall aneurysm model and conventional microcatheters. In vivo experiments in rabbits included aneurysm models (side-wall and bifurcation) and arterial occlusions (carotid and renal).RESULTSAll three designs deployed coils easily and were able to retract coils after partial deployment. Motion was seen in previously released coils and in the catheter when using the clamped ball and looped ribbon designs. The interlocking cylinder design did not cause similar motion. When compared with the other two designs, the interlocking cylinder had significantly greater separation forces between coil pusher and coil while in the catheter. Frictional forces within the catheter were lower for the interlocking cylinder mechanically detachable coil design than for a commercially available conventional coil and coil pusher system. During in vivo testing, the mechanically detachable coil design operated smoothly in the catheter, providing good release and retraction in aneurysms and straight vessels.CONCLUSIONThe interlocking cylinder mechanically detachable coil design is superior to the other two tested designs. The mechanically detachable coil was reliably delivered and detached in in vivo testing for the treatment of aneurysms and for the occlusion of blood vessels.     

A longitudinal study of age-associated memory impairment

An 8-year longitudinal study of elderly people has provided data concerning age-associated impairment (AAMI). In 1985 a random sample of 146 persons aged 65 years or more, living in their own homes, were assessed using the Guild Memory Test the Mini–Mental State Examination (MMSE) and other ratings. After excluding 21% of the sample because they scored less than 24 on the MMSE, and another 34% who fulfilled other exclusion criteria, some 48% of the remainder (22% of the total sample) clearly fulfilled NIMH criteria for AAMI and a further 36% (16% of the total sample) were recorded as forgetful. The NIMH criteria are appropriate for certain research purposes but not in assessing prevalence of memory disorders. Follow–up interviews were conducted after 2, 4, 6 and 8 years. The mortality rate and development of dementia among those fulfilling criteria for AAMI appeared similar to the other non-demented groups of subjects; the mortality rate of those with MMSE scores below 24 was significantly higher. Guild test results at 2-yearly intervals showed considerable changes; half of those scoring least well who were retested showed improvement.     

Correlation of pressure measurements with angiographic characteristics predisposing to hemorrhage and steal in cerebral arteriovenous malformations.

PURPOSETo determine whether there is a physiologic explanation for the predisposition of patients with certain angiographic characteristics to symptoms of hemorrhage and steal.METHODSSuperselective transcatheter feeding arterial pressure and mean arterial pressure measurements were obtained before embolotherapy in 32 patients with cerebral arteriovenous malformations. Pressures were correlated with previously described angioarchitectural characteristics predisposing to hemorrhage and steal. These included size of the arteriovenous malformation, feeding artery length, venous drainage pattern, and angiomatous change.RESULTSThe feeding arterial pressure and feeding arterial pressure/mean arterial pressure ratios were significantly decreased in patients with angiomatous change. Feeding arterial pressure and feeding arterial pressure/mean arterial pressure ratios progressively decreased as lesions went from peripheral, to mixed, to central venous drainage. A trend for lower feeding arterial pressure was also demonstrated with greater feeding pedicle length. A statistically significant correlation could not be demonstrated between feeding arterial pressure or feeding arterial pressure/mean arterial pressure ratios and size of the arteriovenous malformation, hemorrhage, or symptoms of steal.CONCLUSIONSFeeding arterial pressure measurements help provide a physiologic basis for the relationship between certain angiographic characteristics and hemorrhage and steal symptoms in patients with arteriovenous malformation.     

Acute marijuana effects on human risk taking.

Previous studies have established a relationship between marijuana use and risky behavior in natural settings. A limited number of laboratory investigations of marijuana effects on human risk taking have been conducted. The present study was designed to examine the acute effects of smoked marijuana on human risk taking, and to identify behavioral mechanisms that may be involved in drug-induced changes in the probability of risky behavior. Using a laboratory measure of risk taking designed to address acute drug effects, 10 adults were administered placebo cigarettes and three doses of active marijuana cigarettes (half placebo and half 1.77%; 1.77%; and 3.58% Delta9-THC) in a within-subject repeated-measures experimental design. The risk-taking task presented subjects with a choice between two response options operationally defined as risky and nonrisky. Data analyses examined cardiovascular and subjective effects, response rates, distribution of choices between the risky and nonrisky option, and first-order transition probabilities of trial-by-trial data. The 3.58% THC dose increased selection of the risky response option, and uniquely shifted response probabilities following both winning and losing outcomes following selection of the risky option. Acute marijuana administration thereby produced measurable changes in risky decision making under laboratory conditions. Consistent with previous risk-taking studies, shifts in trial-by-trial response probabilities at the highest dose suggested a change in sensitivity to both reinforced and losing risky outcomes. Altered sensitivity to consequences may be a mechanism in drug-induced changes in risk taking. Possible neurobiological sites of action related to THC are discussed.     

Structure-function studies in a series of carboxyl-terminal octapeptide analogues of anaphylatoxin C5a.

The synthesis and structure-activity relationships of C-terminal octapeptide analogues of anaphylatoxin C5a have been studied. The introduction of hydrophobic amino acids into the N-acetylated native octapeptide (N-Ac-His-Lys-Asp-Met-Gln-Leu-Gly-Arg-OH) (1) has led to an analogue with 100 times more activity than the native octapeptide in inhibiting the binding of 125I-labeled anaphylatoxin C5a to human neutrophil membrane receptors. The observed apparent binding Ki's for the compounds (8-10) are in the range of 1-3 microM, and they possess nearly full agonist activity, despite the fact that these analogues are one-eighth or -ninth the size of the natural ligand anaphylatoxin C5a.     

Biomarker monitoring of a population residing near uranium mining activities.

We investigated whether residents residing near uranium mining operations (target population), who are potentially exposed to toxicants from mining waste, have increased genotoxic effects compared with people residing elsewhere (reference population). Population surveys were conducted, and 24 target and 24 reference residents were selected. The selected subjects and controls were matched on age and gender and they were nonsmokers. Blood samples were collected for laboratory studies. The standard cytogenetic assay was used to determine chromosome aberration frequencies, and the challenge assay was used to investigate DNA repair responses. We found that individuals who resided near uranium mining operations had a higher mean frequency of cells with chromosome aberrations and higher deletion frequency but lower dicentric frequency than the reference group, although the difference was not statistically significant. After cells were challenged by exposure to gamma-rays, the target population had a significantly higher frequency of cells with chromosome aberrations and deletion frequency than the reference group. The latter observation is indicative of abnormal DNA repair response in the target population.