The NAIMS cooperative pilot project: Design, implementation and future directions

The North American Imaging in Multiple Sclerosis (NAIMS) Cooperative represents a network of 27 academic centers focused on accelerating the pace of magnetic resonance imaging (MRI) research in multiple sclerosis (MS) through idea exchange and collaboration. Recently, NAIMS completed its first project evaluating the feasibility of implementation and reproducibility of quantitative MRI measures derived from scanning a single MS patient using a high-resolution 3T protocol at seven sites. The results showed the feasibility of utilizing advanced quantitative MRI measures in multicenter studies and demonstrated the importance of careful standardization of scanning protocols, central image processing, and strategies to account for inter-site variability.

Carrier Detection Of Haemophilia A In Pregnancy By Measurement Of Factor VIIIc/Rag And VIIICAg/RAg Ratios

The 1977 WHO Memorandum on carrier detection highlighted the need to test the methods in pregnancy, when plasma modalities of facor VIII are augmented. At KCH blood was taken into citrate from 21 pregnant obligate carriers of severe haemophilia A and 28 pregnant women from unaffected families, matched for age and period of gestation. The women, who were basal after a night’s rest, were tested prior to prenatal diagnosis of haemophilia or other conditions, or to undergoing termination of pregnancy for unrelated causes.One-stage factor VIIIC assays were done immediately; VIIIRAg (Laurell) after -40°C storage within 6 days; and VIIICAg immunoradiometrically in Cardiff on the remainder after varying intervals. Careful standardization was ensured between both laboratories.At 17-22 weeks, VIIIRAg was elevated both in pregnant controls & carriers]; VIIIC & VIIICAg levels were also raised, though less, in the controls (values in units/dl)In pregnant carriers, VIIIC & VIIICAg are both lower than VIIIRAg (p<0.001). Likelihood ratios of carrier probability were plotted by the unequal variances predictive method: VIIIC/RAg discriminated much better between carriers & controls than VIIICAg/RAg, due to the wider spread of VIIICAg in each group, and unlike the findings in a related study of non-pregnant haemophilia A carriers.

Discrepancy between results of the Streptozyme test and those of the antideoxyribonulcease B and antihyaluronidase tests

Comparison of the serum titers obtained with the Streptozyme, the antistreptolysin O, the antideoxyribonuclease B, and the antistreptohyaluronidase tests suggested that the Streptozyme test had failed to detect antibodies against streptococcal deoxyribonuclease B and hyaluronidase. Moreover, sera that were negative in the Streptozyme test could be shown by immunodiffusion to possess significant numbers of precipitins against extracellular factors produced by group A streptococci. Follow-up studies on patients with diagnosed streptococcal infections revealed elevated antideoxyribonuclease and streptohyaluronidase titers and increased numbers of precipitation lines without simultaneous increased titers by the Streptozyme test. There is thus a need for stricter control of possible batch-to-batch variations and more careful standardization of the antigen content of the Streptozyme test.

The effects of mitotic inhibitors on the structure of vinblastine-induced tubulin paracrystals from sea-urchin eggs

Vinblastine sulphate (VLB) is known to induce in vivo formation of tubulin paracrystals in sea-urchin eggs. Corresponding paracrystals have been prepared in the presence of both vinblastine sulphate and other mitoclasic agents. Careful standardization of conditions was required to restrict the formation of alternative forms of the paracrystals induced by vinblastine alone. Comparisons were made between preparations in terms of paracrystal shape, size, proportion of eggs containing paracrystals, number per egg and their relative times of first appearance. A correlation between such properties were established. Comparison of paracrystals at the ultrastructural level showed them all to be similar regardless of the drugs present during their formation. The implications of tubulin polymerization in the presence of mitoclasic agents are discussed and mechanisms for paracrystal enhancement by combinations of such drugs are suggested. Some similarities of paracrystal and microtubule seeding are discussed together with the activation of tubulin in the pool.

THE STANDARDIZING OF A LABORATORY METHOD FOR COMPARING THE TOXICITY OF CONTACT INSECTICIDES

Toxicity tests were conducted with nicotine sulphate and nicotine alkaloid using Drosophila melanogaster as the test animal, with a modified Tattersfield atomizer spray machine, and by an immersion technique. One hundred and fifty flies were treated at each concentration each day. Each experiment was replicated 8 or 10 times using 3 to 22 concentrations. Data were analysed by the method of analysis of variance and by means of probits.It appears from the data secured that careful standardization of any technique will be needed to secure comparable results. Results from spraying were the more uniform and consistent. Saponin spreader had a synergistic action with nicotine sulphate. It complicates results and its effect cannot be separated from that of the insecticide. Variations in observed mortalities result from different rates of spray application (slower applications were better), different ages of test animals (day-old flies and flies over four days old were most susceptible), different numbers of test animals per container (increased numbers increased the kill), different populations (these vary greatly in susceptibility), differences in larval and adult nutrition, and the use of different sized fly containers. All these factors must be standardized or accounted for. When this was done variations due to different experimenters were not significant.In general six or eight replications were enough to establish a curve. Analysis of variance on angular transformation values gives a good test for consistency and the method of probits reveals much heterogeneity in the data.

A PHOTOELECTRIC DENSITOMETER FOR USE WITH SUSPENSIONS

A device for quickly and accurately measuring the population density of a suspension of microorganisms, permitting the preparation of yeast suspensions of known density to within 1 per cent error, was constructed with two Visitron photoelectric cells, a single light of high intensity and a good Wheatstone bridge for balancing the currents from the two photoelectric cells. A large Pyrex milk culture tube holding the suspension is placed in the path of one beam of light coming through a small longitudinal slit and thence to one photocell; a second similar slit directs another beam of light upon the second photocell, thus causing dissimilar currents to flow, the ratio of whose magnitudes may be measured by the bridge resistances. A relation between these currents and the relative light intensities is shown, and the one significant unmeasurable variable (the characteristic constant of a photocell) is practically eliminated by the use of a method of ratios. After careful standardization of technique the apparatus proved more accurate than other methods available for the purpose indicated. In rapid use its accuracy may be put safely at 1 per cent for measuring the densities of cultures of approximately the same age and composed of cells having comparable optical characteristics.