Influence of the histamine control on skin reactivity in skin testing

We investigated the effect of the histamine control (1 mg/ml) on the results of skin prick and intradermal testing with bee and wasp venom. Skin tests were done on the patients' forearms: on the right arm the histamine control and the bee venom dilutions, on the left arm the wasp venom dilutions only, at distances of 4-5 cm. In intradermal testing 11 (9%) of 122 patients showed a positive wheal and flare reaction to the bee venom solution positioned next to the histamine control. The subsequent solutions in higher concentrations did not produce any skin reactions. The results of intradermal testing with bee venom did not occur in intradermal testing with wasp venom or in skin prick testing with both allergens. Our results show clearly that in skin prick tests a distance of 4-5 cm is sufficient to avoid false positive skin reactions. However, using the same distance in intradermal testing showed that histamine affects the skin reactions produced by adjacent allergen solutions. Therefore false positive results may occur.     

Superantigen activation and kinetics of cytokines in the Long-Evans rat.

This study was conducted to identify and quantify, over time, selected cytokine responses in Long-Evans rats that were exposed to staphylococcus enterotoxin B (SEB). The kinetics of selected cytokines [interleukin-2 (IL-2), IL-6, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF)] and phenotype and cell cycle analysis of T lymphocytes were determined in Long-Evans rats administered a single intraperitoneal (i.p.) dose of either 50 microg or 500 microg of SEB. Rats injected with 50 microg SEB had significantly elevated levels of IL-2, IL-6 and IFN-gamma in their serum 2 hr post-injection. IL-2 serum levels were significantly elevated at 2 hr and returned to near control values by 12 hr while both IL-6 and IFN-gamma peaked at 6 hr but remained significantly increased at 24 hr post SEB exposure. A 500 microg dose of SEB did not further enhance these cytokine responses. When spleen cells were collected for culture 2 hr after rats were injected i.p. with 50 microg SEB and cocultured with SEB, TNF and IL-6 levels were significantly increased after 2 hr incubation, while IL-2 and IL-6 were significantly elevated at 6 hr. Production of all these cytokines in spleen cell cultures continued to increase over the 24 hr sampled. Peritoneal cells were collected for culture either at 1 hr or 2 hr after injection of either 50 microg or 500 microg of SEB. IL-6 was significantly increased after 1 hr in culture while TNF was significantly increased by 2 hr regardless of whether the cells were harvested 1 or 2 hr after SEB injection. The greatest response for both IL-6 and TNF occurred when cells from animals injected with 50 microg SEB were restimulated in vitro with SEB. The peak levels for IL-6 were at 12 hr post SEB exposure while TNF peaked at 6 hr. The percentage of CD4+ cells was significantly increased at 48 hr and 72 hr post SEB (50 microg) administration while the percentage of CD8+ cells remained similar to control values for the 168-hr test period. A similar pattern was observed in cell cycling where the CD4+ cells proliferated up to 2 days post SEB injection and then were significantly suppressed at day 3. The CD8+ cells were comparable to control values. These studies demonstrate that the cytokine responses in Long-Evans rats exposed to a superantigen are somewhat similar to those that occur in mice and humans, e.g. a rapid short increase in the production of IFN-gamma and TNF that was accompanied by an increase in the production of IL-2. Additional responses noted in this species, however, were a marked increase in IL-6 production, as well as an early increase in the number and cycling of CD4+ cells followed by a down-regulation of these events. These activities occurred in the absence of notable histopathological alteration of lymphoid organs. The results indicate that the Long-Evans rat is an acceptable animal model to investigate the pathogenesis of superantigen-induced disease and that IL-6 may be an active mediator of this process.     

Running training and co-ordination between breathing and running rhythms during aerobic and anaerobic conditions in humans

The study was carried out on ten triathletes, six sprinters and ten subjects not trained in running (controls) to assess the effects of training history on the co-ordination between breathing and running rhythms during running on a treadmill. Three exercise intensities were used: 50%, 80% and 110% of the subject's anaerobic threshold (AT). All three intensities were performed twice: once with spontaneous breathing and once with breathing intentionally co-ordinated to the running rhythm. Heart rate, respiratory parameters and leg movements were continuously recorded. Blood lactate concentrations were measured discontinuously. The degree of co-ordination between running and breathing was quantified as the percentage of inspirations and/or expirations starting during the same phase of step. The results showed that the degree of both spontaneous and intended co-ordination at aerobic exercise intensities was in all three groups the same and increased in all groups with increasing intensity from 50% to 80% of AT; further increase of intensity to 110% of AT was associated with a significant decrease of co-ordination in controls and sprinters, whereas triathletes were able to maintain the same high degree of co-ordination as at 80% of AT. It was concluded that running training of either type at aerobic work loads had no effect on the co-ordination between running and breathing rhythms. At anaerobic intensities, however, the degree of co-ordination between running and breathing rhythms was higher in the endurance trained athletes than in the sprinters or in the untrained subjects. The degree of co-ordination increased with increasing regularity of breathing. The ability to increase intentionally the degree of co-ordination by paced breathing was independent of running training and was lowest at anaerobic exercise intensities.     

Complete genomic screen in Parkinson disease: evidence for multiple genes.

CONTEXT: The relative contribution of genes vs environment in idiopathic Parkinson disease (PD) is controversial. Although genetic studies have identified 2 genes in which mutations cause rare single-gene variants of PD and observational studies have suggested a genetic component, twin studies have suggested that little genetic contribution exists in the common forms of PD. OBJECTIVE: To identify genetic risk factors for idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Genetic linkage study conducted 1995-2000 in which a complete genomic screen (n = 344 markers) was performed in 174 families with multiple individuals diagnosed as having idiopathic PD, identified through probands in 13 clinic populations in the continental United States and Australia. A total of 870 family members were studied: 378 diagnosed as having PD, 379 unaffected by PD, and 113 with unclear status. MAIN OUTCOME MEASURES: Logarithm of odds (lod) scores generated from parametric and nonparametric genetic linkage analysis. RESULTS: Two-point parametric maximum parametric lod score (MLOD) and multipoint nonparametric lod score (LOD) linkage analysis detected significant evidence for linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD = 5.07; LOD = 5.47) in families with at least 1 individual with PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both levodopa-responsive and levodopa-nonresponsive patients. CONCLUSIONS: Our data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.     

Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease.

CONTEXT: The human tau gene, which promotes assembly of neuronal microtubules, has been associated with several rare neurologic diseases that clinically include parkinsonian features. We recently observed linkage in idiopathic Parkinson disease (PD) to a region on chromosome 17q21 that contains the tau gene. These factors make tau a good candidate for investigation as a susceptibility gene for idiopathic PD, the most common form of the disease. OBJECTIVE: To investigate whether the tau gene is involved in idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Among a sample of 1056 individuals from 235 families selected from 13 clinical centers in the United States and Australia and from a family ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs) within the tau gene for association with PD, using family-based tests of association. Both affected (n = 426) and unaffected (n = 579) family members were included; 51 individuals had unclear PD status. Analyses were conducted to test individual SNPs and SNP haplotypes within the tau gene. MAIN OUTCOME MEASURE: Family-based tests of association, calculated using asymptotic distributions. RESULTS: Analysis of association between the SNPs and PD yielded significant evidence of association for 3 of the 5 SNPs tested: SNP 3, P =.03; SNP 9i, P =.04; and SNP 11, P =.04. The 2 other SNPs did not show evidence of significant association (SNP 9ii, P =.11, and SNP 9iii, P =.87). Strong evidence of association was found with haplotype analysis, with a positive association with one haplotype (P =.009) and a negative association with another haplotype (P =.007). Substantial linkage disequilibrium (P<.001) was detected between 4 of the 5 SNPs (SNPs 3, 9i, 9ii, and 11). CONCLUSIONS: This integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD.     

A low molecular weight allergen of white birch (Betula verrucosa) is highly homologous to human profilin

Cloning of allergens has contributed substantially to the understanding of mechanisms in allergic diseases by providing information about the sequence and hence biological functions of allergens. The major birch pollen allergen, Bet v I [Breiteneder H, et al: EMBO J 1989;8:1935-1938] and the white-faced hornet venom allergen (antigen 5) [Si Yun Fang K, et al: Proc. Natl. Acad. Sc. USA 1988;85:895-899] were shown to be highly homologous to pathogenesis-related proteins of plants. In the case of the major allergen of house dust mite, Der p I, homology to proteases was demonstrated. Therefore, the proposed biological function of these IgE-binding proteins might be related to their allergenic potential. In this paper we tentatively identify a ubiquitous family of low molecular weight allergens as profilins. The identification is based on a sequence homology, (b) binding to poly(L-proline), and (c) immunological cross-reactivity. Recombinant birch profilin was purified to homogeneity and showed the same properties as natural profilins.     

The course of extravascular lung water in severely injured patients in intensive care with and without thoracic trauma

In patients with multiple injuries, the development of permeability edema can be assumed. However, no uniform shape of this fluid accumulation can be found even in the presence of severe injuries. Based on the first clinical observations, our aim was to search for correlations between the development of extravascular lung water (EVLW) and the individual injury pattern in severely traumatized ICU patients. PATIENTS and METHODS. Our investigations were performed in 48 artificially ventilated ICU patients. According to the prevailing injury pattern patients were divided into three groups: group A: 18 patients (mean age: 32 years, mean Injury Severity Score (ISS) = 29) with isolated thoracic trauma; group B: 10 patients (mean age: 27 years, mean ISS = 42) with severe multiple trauma but without any thoracic injury; group C: 20 patients (mean age: 33 years, mean ISS = 43) with severe multiple trauma and concomitant thoracic trauma. In all patients (group A, B, C), EVLW was determined by means of a double indicator method on a daily basis from the patient's admission to the ICU (day of trauma) until day 10. Additionally, the hemodynamic parameters (heart rate, mean arterial pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure and cardiac index) were determined at the same time. RESULTS. As shown in Fig 1, EVLW was slightly elevated on day 1. However, on day 2 EVLW decreased within normal values and remained in that range until the end of the observation period. On day 3 a slight and fleeting increase of EVLW, but within normal range, can be seen. In group B (Fig.2), EVLW can be observed within normal range within a period of 4 days. Starting from day 5 until day 7 a marked increase (p greater than 0.01) in EVLW can be seen. From that maximum point EVLW development reverses slightly until day 10--however, without returning to the normal range. In group C, a marked biphasic pattern can be seen due to EVLW maximum values on post-traumatic days 3 and 7. However, in this group the EVLW was in the pathological range during the whole observation period. No statistically significant differences could be seen, when looking at hemodynamic variables. CONCLUSION. Isolated thoracic trauma will not lead to a marked pathological elevation of EVLW within the lungs. Moreover, EVLW decreases rapidly within a short time period. Based on our results, it seems that severe extrathoracic injuries will intensify microvascular injury in the initial period, as shown in our patients in group C. Increase of EVLW at a later time (day 7), as observed in groups B and C, is possibly the expression of a mediator and activator-induced "septiformal" injury of the microvascular endothelium. This may be caused by the underlying massive peripheral soft-tissue trauma. Specific elevations of EVLW subsequent to the individual injury pattern can indicate that that process has begun and is responsible for the origin of the microvascular injuries.     

Eine Skala zur Messung von Beschwerden bei degenerativen Veränderungen der Halswirbelsäule (HWS) Hilfe zur Indikationsstellung und zur Evaluation des Operationserfolgs

A scale for measuring symptoms related to degenerative diseases of the cervical spine is presented. Twenty typical symptoms are listed, e. g., neck pain, dysesthesia, and reduced mobility. Responses are assessed via a 6-point scaling ("did not have symptom" - "had symptom and suffered very strongly".) The cervical spine scale was tested in three samples: patients having undergone cervical spine surgery (n = 70), patients with other orthopedic diagnoses (n = 104), and healthy students (n = 100). The single items of the scale were aggregated into four scores: total number of symptoms, degree of overall symptom distress, functional disability, and pain/psychological distress. Statistical analyses proved the high reliability (Cronbach's alpha = 0.85 to 0.95) and validity (content, convergent, discriminant) of all scores. The scale differs clearly between cervical spine patients, other orthopedic patients and healthy individuals, and between cervical spine patients with different subjective operative outcomes. For applied clinical purposes the cervical spine scale can be included in a quality of life profile (QL-profile); this allows for a readily understandable graphic depiction of individual patients' QL-status.     

A safety and pharmacokinetic study of intravenous natalizumab in patients with MS

A phase 1, randomized, placebo-controlled, five-level dose escalation safety and tolerability and pharmacokinetic study of a single IV dose of natalizumab was performed. Doses of 0.03 to 3.0 mg/kg natalizumab or placebo were studied in 28 stable relapsing-remitting or secondary-progressive MS. All doses were safe and well tolerated in MS. Serum concentrations of natalizumab are detectable for 3 to 8 weeks after a single 1- or 3-mg/kg IV dose and justify controlled efficacy studies.