Comparison of allergenicity and immunogenicity of an intact allergen vaccine and commercially available allergoid products for birch pollen immunotherapy

BACKGROUND: Specific immunotherapy with intact allergen vaccine is a well-documented treatment for allergic diseases. Different vaccine formulations are currently commercially available, the active ingredient either being intact allergens or chemically modified allergoids. The rationale behind allergoids is to decrease allergenicity while maintaining immunogenicity. However, data from the German health authorities based on reporting of adverse events over a 10-year period did not indicate increased safety of allergoids over intact allergens. OBJECTIVE: The objective of this study was to investigate the effect of chemical modification on allergenicity and immunogenicity comparing four commercial allergoid products for birch pollen immunotherapy with an intact allergen vaccine. METHODS: Solid-phase IgE inhibition and histamine release assays were selected as model systems for allergenicity, and a combination of human T cell proliferation and IgG titres following mouse immunizations were used to address the immunogenicity of the intact allergen vaccine and the four allergoids. In all assays, the products were normalized with respect to the manufacturer's recommended maintenance dose. RESULTS: IgE inhibition experiments showed a change in epitope composition comparing intact allergen vaccine with allergoid. One allergoid product induced enhanced histamine release compared to the intact allergens, while the other three allergoids showed reduced release. Standard T cell stimulation assays using lines from allergic patients showed a reduced response for all allergoids compared with the intact allergen vaccine regardless of the cell type used for antigen presentation. All allergoids showed reduced capacity to induce allergen-specific IgG responses in mice. CONCLUSION: While some allergoids were associated with reduced allergenicity, a clear reduction in immunogenicity was observed for all allergoid products compared with the intact allergen vaccine, and the commercial allergoids tested therefore do not fulfil the allergoid concept.     

Magnetic resonance imaging - a method of studying the size and asymmetry of the planum temporale

The planum temporale is a triangular region on the upper surface of the temporal lobe. This area of the brain is important for language processing and shows a left-right asymmetry of size in most brains. Particular interest has been focused on the size and asymmetry of the planum temporale in brains of individuals with developmental dyslexia. Magnetic resonance imaging (MRI) is a method that produces excellent morphological details of organic structures. We have developed an MRI method of studying the size and asymmetry of the planum temporale in human brains. Because of considerable variation of anatomical landmarks in this cortical region of the brain, an evaluation of asymmetry is not possible in all brains. Furthermore, our experience with this method indicates that any indirect imaging technique of studying asymmetry of the planum temporale must be evaluated with caution. With this in mind, however, MRI may give valuable anatomical information about the planum temporale in individuals with anomalous language function.     

Computer-assisted three-dimensional reconstruction of the hippocampal region based on serial sections

A large series of rabbit hippocampal Neo-Timm stained sections were manually aligned, digitized, and by a modified median filtration noise reduced and reconstructed into a three-dimensional object. From the presented simulated grey tone cuts of this object, the reader may assemble a rabbit hippocampal model, that spatially illustrates its anatomy.     

Incidence of multiple sclerosis in Hordaland, western Norway: a fluctuating pattern

The incidence of multiple sclerosis (MS) was studied in the county of Hordaland, western Norway. A significant increase in incidence in the period 1958-1987, a decline followed by a gradual increase in mean age at onset, geographic differences in time trends and a biphasic pattern revealed by a birth cohort analysis support the theory of real time-space fluctuations in the incidence of MS over time.     

Moderate acute rejection detected during annual catheterization in pediatric heart transplant recipients.

BACKGROUND: Acute rejection commonly occurs within the first year after heart transplantation, and then decreases in frequency with time. Recently, the long-term utility of endomyocardial biopsy during routine annual catheterization has been questioned. The purpose of this study was to retrospectively review the prevalence of biopsy-proven rejection during routine annual catheterization in our patient population, determine whether biopsies late after transplant are useful, and identify factors that correlate with late unsuspected rejection. METHODS: Biopsy results from the annual catheterization were evaluated from 1986 to August 2000. The prevalence of moderate rejection was evaluated and compared with the patient's immunosuppressive regimen; the prevalence of late rejection; and how late rejection correlated with recipient age, number of first-year rejections and presence of sub-therapeutic cyclosporine. RESULTS: A total of 1108 biopsies were performed in 269 children with a mean follow-up of 5 +/- 3 years (median 5 years, range 1 to 11 years). Three-drug immunosuppressive therapy, including steroids, was used in 93 patients. There was a persistent 8% to 10% prevalence of moderate rejection at up to 10 years post-transplantation. Moderate rejection was more likely in patients: (1). on 3-drug immunosuppressive therapy; (2). with a recipient age >1 year; and (3). with a relatively lower cyclosporine level. CONCLUSIONS: These data suggest that continued surveillance of pediatric transplant patients for acute rejection is indicated for long-term follow-up.     

Evaluation of Enoxaparin Given before and after Operation to Prevent Venous Thromboembolism during Digestive Surgery: Play-the-Winner Designed Study

A total of 316 patients were included in a play-the-winner (PTW) designed study comparing the safety of enoxaprain started preoperatively versus postoperatively as prophylaxis against venous thromboembolism for digestive surgery. In a PTW-designed study the treatment of any next patient depends on the outcome of the previous patient. If successful, the next patient receives the same treatment, if not, the comparative regimen is given. Excessive bleeding according to specified criteria, severe adverse reactions, clinically detected deep venous thrombosis (DVT), or pulmonary embolism (PE) were criteria for classification as “loser.” The PTW design allocates most patients to the superior treatment. The main variable in PTW studies is the number of consecutive patients receiving the same treatment. In this study 163 patients were allocated to postoperatively started and 153 to preoperatively started prophylaxis with enoxaparin. The frequency of “winners” was found to be 82.8% and 78.4% in the post- and preoperatively treated groups, respectively. No significant differences were found between the groups with regard to frequency of “winners” or the number of consecutive patients before change of treatment. The percentile of survival distribution did not detect superiority of any group. Prophylaxis against postoperative venous thromboembolism for digestive surgery using enoxaparin can safely be started preoperatively.     

Seroepidemiological characterization of a syphilis epidemic in the Republic of the Marshall Islands, formerly a yaws endemic area.

The annual numbers of reported cases of syphilis in the Republic of the Marshall Islands (RMI) increased from none in 1983 to more than 600 in 1989, suggesting a large outbreak of syphilis. Much of the increase resulted from expanded serological screening. The apparent outbreak of syphilis, therefore, may have been partly the result of increased surveillance or, since the RMI was formerly a yaws endemic area, possibly due to a resurgence of yaws. To address this problem and better characterize the epidemic, we analysed results from a 1989/90 Ministry of Health Services mass serological screening on Majuro Atoll, the main population centre. Serum specimens from 9160 people (86% of residents aged 15-44 years) on Majuro were screened with the rapid plasma reagin (RPR) card test; we repeated the RPR and performed a confirmatory microhaemagglutination assay for Treponema pallidum-specific antibodies (MHA-TP) on a sample of serum specimens. To estimate the seroprevalence of syphilis, we also tested a sample of RPR nonreactive specimens by MHA-TP. Among people less than 45 years of age, total (11.5%) and high-titre (5.2%) seropositivity rates were highest in the 20-24 year age group, as was MHA-TP seroprevalence (15.9%). These results suggested that a large outbreak of syphilis was responsible for the observed seroreactivity. Cumulative incidence modelling and comparisons with the results of a previous serosurvey conducted in 1985 suggested that the duration of the syphilis epidemic was approximately 10 years and that incidence had not increased appreciably since 1985.     

Identification of urinary metabolites of 8-methyl-8-azabicyclo- 3,2,1] octan-3-yl 3,5-dichlorobenzoate (MDL 72,222) in the dog and monkey.

The metabolism of 8-methyl-8-azabicyclo- 3,2,1]octan-3-yl 3,5-dichlorobenzoate (MDL 72,222) was studied in the dog and monkey. Four urinary metabolites were detected by HPLC, HPLC/MS, and GC/MS, and were identified by comparison to authentic standards. The major metabolite in the dog, approximately 41% of the administered dose excreted between 0 and 120 hr, was the MDL 72,222-N-oxide. On the other hand, the major metabolite in the monkey was the glycine conjugate of 3,5-dichlorobenzoic acid (greater than 56% of the dose). Seven percent of the dose in the monkey urine was free 3,5-dichlorobenzoic acid. N-Desmethyl MDL 72,222 was present at 2.5 and 1% in the dog and monkey, respectively. Very little (less than 1%) of the parent compound was found in urine. The major pathways of metabolism of MDL 72,222 are N-oxidation, N-demethylation, ester hydrolysis, and amino acid conjugation.     

Partial defluoridation of drinking water using fluorapatite precipitation.

Ion adsorption and ion exchange are two methods commonly used in small home units to treat drinking water to bring the fluoride concentration to within acceptable limits. However, the necessary flowthrough system is often difficult to arrange where there is no piped supply and gradual exhaustion of the active agent is not easily detected. In an attempt to overcome these problems a defluoridation method based on the precipitation of a sparingly soluble fluoride salt, fluorapatite, has been studied. Samples of simulated high-fluoride drinking waters, approximately 10 ppm F, were saturated with brushite, resulting in a state of supersaturation with respect to fluorapatite. Subsequent seeding with hydroxyapatite caused a lowering of the calcium, phosphate, and fluoride concentrations in solution, indicative of fluorapatite precipitation. Repeating the process had an additive effect. Bone char was a less effective seed than hydroxyapatite with water containing fluoride only, but was a more effective seed with simulated Kenyan borehole water containing additional salts. Sixty-minute brushite saturation and apatite seeding steps were generally more effective than 10-min steps. The results suggest that apatite coprecipitation may be a convenient low-technology way to defluoridate drinking water, although prior testing might be useful to ensure adequate removal of fluoride.