Versuche einer passiven Übertragung der Tuberkuloseimmunität an Schafen

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A further evaluation of the clinical use of specific IgE antibody testing in allergic diseases

BACKGROUND: The evaluation and interpretation of the results from blood tests measuring specific immunoglobulin E (IgE) antibody concentration is currently made using the dichotomized result from the test despite a quantitative result is obtained. It has been shown that different levels of IgE antibodies, assessed by blood test and skin prick test, may have a relation to presence of symptoms, implying that there is more information in a quantitative result than in the dichotomous--positive or negative. OBJECTIVE: To investigate the clinical utility of quantification of IgE antibodies in the diagnosis of allergic patients and whether such procedure has any advantage to the presently dichotomously used sensitivity and specificity at a fixed cut-off. METHODS: Data from a previously published study (R. Paganelli, I.J. Ansoteugi, J. Sastre, C.-E. Lange, M.H.W.M. Roovers, H. de Groot, N.B. Lindholm, P.W. Ewan, Allergy, 1998; 53) analysing diagnosis of allergic patients in four different clinics were re-evaluated. In the original study consecutive patients with suspected IgE-mediated allergy had been examined and evaluated according to the clinical routine at each clinic, using case history, physical examination, skin tests and laboratory tests, except the test to be evaluated, and given a "doctors' allergen-specific diagnosis" as positive or negative. In the present study the relation between "doctors' allergen-specific diagnosis", expressed as pos/neg, and the quantitative levels of specific IgE antibody concentration was analysed using a logistic regression model. This presentation of results was also compared with the more common characteristics of sensitivity and specificity, and also with Receiver-operator characteristics (ROC) curves. RESULTS: The used logistic model described the relationship between allergen-specific diagnosis in each study and the levels of IgE antibodies. The shape of the curve illustrated the physicians' disposition for a positive diagnose in the study, in relation to the specific IgE antibody level. Differences in the shape of the curve was found both between allergens within clinics and between clinics for the same allergen. No association could be demonstrated between prevalence and shape of the curve. CONCLUSIONS: Conventional sensitivity/specificity figures or ROC concepts only use the qualitative statement of whether IgE is present or not. A risk assessment using the quantitative level of IgE antibody to an allergen increases the utility of the information in clinical context compared with a qualitative statement of whether IgE is present or not. The quantification demonstrated the link between specific IgE antibodies and allergic reactions. The use of objective, well performing quantitative tests should help improve diagnostic accuracy and might provide a way for the patient to understand and manage his or her daily situation and risk for reactions.     

Minimal residual disease in childhood B-lineage lymphoblastic leukemia. Persistence of leukemic cells during the first 18 months of treatment

BACKGROUND. Whether patients in clinical remission for acute lymphoblastic leukemia (ALL) continue to harbor leukemic cells is not known, because methods of detecting residual malignant cells have not been sufficiently sensitive. This information might be useful for predicting recurrence and determining the duration of therapy. METHODS. Using a sensitive new method--identifying complementarity-determining region III sequences with the polymerase chain reaction--we estimated the number of residual leukemic cells in the bone marrow of eight children with B-lineage lymphoblastic leukemia before and after remission. RESULTS. Induction chemotherapy produced a 3-to-4-log reduction in the number of leukemic cells. In all samples obtained up to 18 months after diagnosis, however, 0.004 to 2.6 percent of bone marrow nucleated cells were residual leukemic cells. Among the four patients studied more than 18 months after diagnosis, three had no detectable leukemic cells in marrow samples. Despite this, one of them, who was no longer receiving therapy, had a central nervous system relapse. In one patient receiving maintenance chemotherapy, there was a 60-fold increase in leukemic cells three months before bone marrow relapse. CONCLUSIONS. The complete disappearance of leukemic cells (or their reduction below our method's threshold of detection, 1 in 100,000 cells) may be necessary to achieve a cure of ALL. The quantification of residual leukemic cells in serial marrow aspirates during therapy may allow the early detection of relapse.     

Immunogenetic studies in families with rheumatoid arthritis and autoimmune thyroid disease.

HLA and Gm typing were carried out in 16 families. Seven families included 10 sib pairs with rheumatoid arthritis (RA) and autoimmune thyroid disease (ATD) respectively, and nine families included 16 sib pairs with RA and circulating thyroid autoantibodies respectively. Eight, 11, and seven sib pairs with either RA or clinical or immunological evidence of ATD shared none, one, and two HLA haplotypes respectively, and two, seven, and two informative sib pairs shared none, one, and two Gm haplotypes respectively. This random haplotype sharing of HLA and Gm haplotypes suggests that non-HLA, non-Gm linked genes are likely to be involved in any genetic predisposition common to RA and ATD.     

Histological and ultrastructural appearance of the hydroxyapatite-bone interface

This article describes the histological and ultrastructural appearance of the interface created in the implantation bed, between bone tissue and implants made of dense sintered hydroxyapatite (HA). Biopsies from dog subjects included: a) loaded permucosal dental implants for tooth substitution, b) subperiosteally placed implants for alveolar bone correction, c) endosseously placed dental root implants to retain ridge form following extraction. The light and electron microscopical results show extensive bone apposition on the osseous sides of the implant surfaces. There is an intimate, direct bone contact without any visible interruption. The bone is of normal lamellar type and continuously connected with the trabecular bone. Bone has grown into the finest surface irregularities of the implant. Collagen fibers of the calcified bone matrix are observed within a distance less than 500 A from the implant surface. The thin (20-100 A) electron dense layer at the bone-implant interface resembled the lamina limitans of organic bone matrix, also seen at the inner walls of the osteocytes lacunes. Deposition of bone gives rise to a biologically stable bone-implant interface, without disturbance of the physiological bone turnover. This is seen as very favorable for desired long term fixation of implant to bone.     

Three-year durability of dual-nucleoside versus triple-nucleoside therapy in a Thai population with HIV infection

We compared the long-term immunologic and virologic efficacy of the dual- and triple-nucleoside therapy for HIV infection. This was a retrospective analysis of 2 randomized clinical trials in antiretroviral-naive patients. In the dual-nucleoside group, 15 started with didanosine (ddI) monotherapy and then added stavudine (d4T) after 24 weeks, 63 started with various doses of d4T and ddI, and 53 started with zidovudine (ZDV) and lamivudine (3TC). In the triple-nucleoside group, 53 started with ZDV, 3TC, and ddI. After 48 weeks, patients who were not failing were randomized to immediate (before treatment failure) versus delayed (at the time of virologic failure) switching from ddI and d4T to ZDV and 3TC or vice versa and from ZDV, 3TC, and ddI to d4T, 3TC, and abacavir (ABC). Failure was defined as a plasma HIV-1 RNA level>or=1 log10 above nadir or >or=10,000 copies/mL when nadir was <500 copies/mL. Patients failing therapy before week 48 received the new treatment as in the immediate switching group. Hydroxyurea was added to the last treatment regimen if patients failed after week 96. CD4 count and plasma HIV-1 RNA level (branched DNA assay with a cutoff point of 50 copies/mL) at week 144 were analyzed by intention to treat. Compared with the dual-nucleoside group, the triple-nucleoside group had a higher proportion of patients with <50 copies/mL at 144 weeks (60% vs. 18%; P<0.001), higher median CD4 count (388 cells/microL vs. 346 cells/microL; P=0.018), and longer duration of response, defined as the time from onset of viral suppression (<500 copies/mL) to the time of treatment failure (the first of 2 consecutive HIV-1 RNA measurements >500 copies/mL never followed by 2 consecutive visits showing suppressible viremia to <500 copies/mL) or discontinuation from the study (144 weeks vs. 104 weeks; P=0.002). Multivariate regression analyses showed that significant predictors for treatment success, defined as a plasma viral load <50 copies/mL at week 144, were asymptomatic clinical status at enrollment, a baseline plasma viral load 相似文献   

Significant differences between plasma HIV-1 RNA assays in HIV-1 subtype E infected patients treated with antiretroviral therapy

A total of 72 HIV-1 infected Thai patients treated with didanosine (ddI) or stavudine (d4T) plus ddI at the time of interim analysis were analyzed. Sixty patients (83%) carried subtype E documented by HIV-1 V3 serotyping. HIV-1 RNA levels were measured using three commercial viral load assays. At baseline (n = 57), Quantiplex 2.0 and NucliSens 2.0 showed mean log10 HIV-1 RNA of 0.7 log10 or 5 fold lower than Amplicor 1.5 (mean 4.29 versus 5.0 log10, respectively, p < 0.001). At week 20 of treatment (n = 29), HIV-1 RNA levels were detected in 55.2%, 31%, and 33.5% of subjects tested by Amplicor 1.5, Quantiplex 2.0, and NucliSens 2.0, respectively. In conclusion: plasma HIV-1 RNA analyses showed comparable values with Quantiplex 2.0 and NucliSens 2.0 assays. In contrast, Amplicor 1.5 resulted in approximately 5 folds higher HIV-1 RNA levels and a 25% higher rate of detection of plasma HIV-1 RNA as compared to the other two assays. As the current goal of therapy is to suppress plasma viral load below the detection limit of the assays, the significant differences between the assays may influence antiretroviral efficacy evaluation and management.     

Evidence for an Association of the Dopamine D5 Receptor Gene on Age at Onset of Attention Deficit Hyperactivity Disorder

The purpose of this study was to determine whether the single nucleotide polymorphisms (SNPs) within candidate genes for attention deficit hyperactivity disorder (ADHD) are associated with the age at onset for ADHD. One hundred and forty-three SNPs were genotyped across five candidate genes ( DRD5 , SLC6A3 , HTR1B , SNAP25 , DRD4 ) for ADHD in 229 families with at least one affected offspring. SNPs with the highest estimated power to detect an association with age at onset were selected for each candidate gene, using a power-based screening procedure that does not compromise the nominal significance level. A time-to-onset analysis for family-based samples was performed on these SNPs to determine if an association exists with age at onset for ADHD. Seven consecutive SNPs surrounding the D5 dopamine receptor gene ( DRD5 ), were associated with the age at onset for ADHD; FDR adjusted q-values ranged from 0.008 to 0.023. This analysis indicates that individuals with the risk genotype develop ADHD earlier than individuals with any other genotype. A haplotype analysis across the 6 significant SNPs that were in linkage disequilibrium with one another, CTCATA , was also found to be significant (p-value = 0.02). We did not observe significant associations with age at onset for the other candidate loci tested. Although definitive conclusions await independent replication, these results suggest that a variant in DRD5 may affect age at onset for ADHD.