Co-registration of PET and MRI in different courses of MS using Cobalt-55 as a Calcium-tracer.

Multiple Sclerosis (MS) is an auto-immune central nervous system (CNS) inflammation. At this moment, MRI is the most accurate paraclinical test in MS to monitor disease activity, although poorly correlated with clinical impairment. PET using Co-55 as a Ca-tracer may visualize Co-transport across the neuronal membrane, Ca-mediated inflammatory processes and passive leakage through a breach in the blood-brain barrier. Co-registration of MRI and Co-PET may actually allow identification of clinically active lesions. MRI and Co-PET were performed as described elsewhere. Based on a statistic parametric mapping (SPM-96)-software package, MRI and Co-PET were superimposed. A semi-automated technique was used to count the MS-lesions. We included four groups of eight MS-patients with relapsing-remitting (RR), primary progressive (PP), progressive relapsing (PR) and secondary progressive (SP) courses and eight healthy volunteers. MS was assessed in terms of impairment using Kurtzke's Expanded Disability Status Scale (EDSS) and Scripps Neurological Rating Scale (NRS). Co-PET displayed focal uptake throughout the MS brain, both in the grey and white matter. All four patients groups (as compared to controls) demonstrated a more inhomogeneous distribution of Co-spots with a tendency to show clustering, most evident in RR-MS. SPM-analysis revealed an essentially different distribution pattern of MS spots on MRI and Co-PET. (Merging of) Co-PET and MRI may eventually form complementary tools for identifying clinically relevant lesions, thus providing a more reliable secondary outcome measure in MS.

Poor biologic activity of cross-reactive IgE directed to carbohydrate determinants of glycoproteins.

BACKGROUND: In our outpatient population, approximately one third of patients sensitized to grass pollen were found to have significant serum levels of anti-peanut IgE in the RAST, without positive peanut skin prick test (SPT) response and without peanut-related allergic symptoms. It was suggested earlier that poor biologic activity of IgE antibodies directed to cross-reactive carbohydrate determinants (CCD) of glycoproteins might explain these discrepancies. OBJECTIVE: In this study we investigated the biologic activity of IgE directed to CCD. METHODS: Sera of 32 patients allergic to grass pollen with significant levels of anti-peanut IgE, a negative response on peanut SPT, and no symptoms of peanut allergy were tested for the presence of anti-CCD IgE. Eleven of these patients with greater than 3.0 IU/ml anti-peanut IgE (patients 1 to 11) were selected together with four control patients allergic to peanut, on the basis of a positive response on peanut SPT and a history of peanut allergy (patients 12 to 15). Inhibition of the peanut RAST was performed by using proteinase K-treated grass pollen extract as a CCD source. Basophil histamine release assays (BHRAs) were performed with peanut extract and the isolated peanut major allergens Ara h 1 and Ara h 2. In addition, intracutaneous tests with peanut extract were performed. RESULTS: In 29 (91%) of 32 patients with discrepant peanut RAST and SPT responses, anti-CCD IgE (> or =0.1 IU/ml) was detected. In patients 1 to 11 almost complete inhibition of the peanut RAST with CCD was found (94.3% +/- 5.5%; mean +/- SD). In contrast, in the patients allergic to peanut only partial inhibition (59%) was found in one subject (p = 0.002, Mann-Whitney test). In the BHRAs and the intracutaneous tests of patients with discrepant peanut RAST and SPT results, reactivity was found only at high concentrations of peanut allergens. When related to specific IgE levels, reactivity to peanut allergens in the BHRAs of these patients was found to be at least a factor of 1000 less when compared with reactivity to control inhalant allergens. CONCLUSION: We conclude that cross-reactive IgE directed to carbohydrate determinants of glycoproteins, as found in grass pollen-sensitized patients, has poor biologic activity. It can therefore cause positive RAST results without apparent clinical significance.

Allergen-induced changes in airway responsiveness are related to baseline airway responsiveness.

In the literature, bronchial allergen challenge is usually reported to result in an increase in histamine-induced airway responsiveness (AR). The present study investigated the relation between baseline AR and allergen-induced changes in AR. The effect of allergen challenge on AR was investigated in 21 atopic asthmatic patients. Allergen challenge resulted in a significant decrease in PC20 histamine after 24 h. When the group was divided into three subgroups according to baseline PC20 histamine, a significant decrease in PC20 histamine was found only in patients with relatively high baseline PC20 histamine (groups 1 and 2). A significant inverse correlation was found between baseline PC20 and allergen-induced PC20 histamine. The effect of repeated allergen challenge on AR was studied in eight patients. The first allergen challenge resulted in a significant decrease in PC20 histamine; no further decrease in mean PC20 histamine was seen after the second allergen challenge. These results suggest that allergen-induced changes in AR occur mainly in patients with relatively high baseline PC20 values. Once an increase in AR is induced, further allergen challenge does not always result in further increase in AR.

The relationship between RAST and skin test results in patients with asthma or rhinitis: a quantitative study with purified major allergens.

BACKGROUND: Study of the relationship between skin test results and IgE antibody levels is seriously hampered by the use of conventional allergen extracts because the precise amount of relevant allergen for each patient is unknown. OBJECTIVE: This study was designed to investigate skin reactivity with purified major allergens and to assess the relation with serum levels of IgE antibodies and to determine which additional factors contribute to the skin test result. METHODS: We used five purified major allergens (Der p 1, Der p 2, Fel d 1, Lol p 1, and Lol p 5) in skin tests, RASTs, and histamine release tests in 43 multisensitized patients with asthma or rhinitis. RESULTS: The differences in biologic activity of the five major allergens at a given level of specific IgE are within one order of magnitude. A significant residual variation remains in the correlation between skin test results and levels of IgE antibodies, which cannot be explained by imprecision of both tests (Pearson log skin test vs log specific IgE: r = 0.46-0.92). With similar levels of specific IgE, the amount of allergen that is required for a positive skin test result may differ by as much as a factor of 100 between patients. The amount of total IgE in serum contributes significantly to the skin test result. High values of total IgE are accompanied by a lower skin reactivity for allergen. Within individuals, allergens that cause skin test results that deviate from the prediction based on IgE antibody level often show a similar deviation in the histamine release test. This indicates that the type of IgE response (i.e., affinity or epitope recognition pattern) contributes significantly to the skin test result. Skin reactivity for histamine does not significantly influence the skin reactions expressed as allergen threshold. However, increased skin reactions with higher allergen dosages depend on histamine reactivity. CONCLUSION: The major allergens tested show similar biologic activities. In addition to IgE antibody level, total serum IgE and type of IgE antibody response contribute significantly to the skin test threshold for allergens. Even in a system with purified allergens, IgE antibody levels and skin test results are not interchangeable as an indicator of the degree of allergic sensitization.

Whole-lung lavage under hyperbaric oxygen conditions for alveolar proteinosis with respiratory failure.

Whole-lung lavage under hyperbaric oxygen conditions was performed in two patients suffering from severe respiratory insufficiency in pulmonary alveolar proteinosis. Under these conditions, gas exchange was maintained and the mixed venous partial pressure of oxygen and oxygen saturation showed increases to acceptable levels. This enabled us to limit the FIO2 in order to extend the oxygen tolerance and to perform lavage procedures more effectively. Both patients showed a very significant improvement of their clinical course, and we conclude that elective use of hyperbaric oxygen in unilateral lung lavages should be considered in these severe cases.