Identification of human T-cell epitopes on the S4 subunit of pertussis toxin.

Ten adult humans were vaccinated with the Japanese acellular pertussis vaccine JNIH-3, containing detoxified pertussis toxin (PT), formaldehyde, and filamentous hemagglutinin. The vaccination induced a specific antibody response to PT and filamentous hemagglutinin, and a Western blot (immunoblot) analysis of the antibody response to PT revealed antibodies to PT subunits S1, S2, S3, S4 and S5. The response of peripheral lymphocytes to PT was assessed in an in vitro proliferation assay. A proliferative response to detoxified PT and PT dimers S2-S4 and S3-S4 was found, and it was further demonstrated that the proliferative response to detoxified PT and dimer S2-S4 was mediated by T cells of the CD4+ phenotype. The specificity of the proliferative response to subunit S4 was analyzed with a range of synthetic peptides synthesized on the basis of the primary sequence of subunit S4. The proliferative response to the peptides revealed two major and one minor T-cell epitope located in the NH2-terminal end of subunit S4.     

Definition of An Optimal First-line Chemotherapy in Metastatic Breast Cancer

Single-agent chemotherapy of metastatic breast cancer is the treatment of choice in patients with slow tumor progression and asymptomatic disease. In this patient group, the choice of drugs is based more on good tolerability than on efficacy. By contrast, symptomatic or rapidly progressing disease requires the use of highly active regimens where more weight is put on reliable antitumor activity. While anthraycline-based combination regimens have set the standard of effective treatment, the addition of docetaxel (and to a lesser extent paclitaxel) has improved tumor response, but failed to induce a consistent prolongation of survival. Based on retrospective analyses, it is hypothesised that the combined use of anthracyclines and taxanes in first-line therapy may be most beneficial in defined subgroups: after adjuvant chemotherapy, in patients with HER-2 gene amplification, possibly also in patients with rapidly progressing visceral disease.     

Vertebroplasty and Kyphoplasty in Spinal Trauma

Abstract Kyphoplasty and vertebroplasty have become recognized procedures for the treatment of vertebral fractures, especially in patients with osteoporosis. In most cases of osteoporotic spinal vertebral fracture in elderly patients, polymethylmethacrylate (PMMA) cement is used to fill the defect and stabilize the vertebral body. The techniques of vertebroplasty and kyphoplasty differ in the possibility of realignment and reconstruction of the vertebral body and spinal column. Long-term results in terms of integration of the cement and bioreactivity of the vertebral body are still lacking; so, these procedures are still no options in the treatment of younger patients. Vertebroplasty and kyphoplasty show different success in the management of fresh traumatic spine fractures. The acute traumatic vertebral fracture has to be classified sensitively, to find the right indication for cement augmentation. Mild acute compression fractures can be treated by vertebroplasty or kyphoplasty, severe compression and burst fractures by combination of internal fixation and kyphoplasty. The indications for use of biological or osteoinductive cement in spinal fracture management must still be regarded as restricted owing to the lack of basic biomechanical research data. Such cement should not be used except in clinical studies.     

SKIN FERMENTS

That a definite change in the reactivity of the skin takes place during the transition from infancy to childhood has been repeatedly noted. Rolly (5), working with a variety of bacterial toxins, found that infants did not react, but that reactions occurred with advancing age. Similarly Tenner (6), using Witte''s peptone, colon bacilli, and tuberculin observed that at about the period that the skin of children became increasingly sensitive to tuberculin, a corresponding reactivity was manifest toward the other antigens. It seems possible to us that this phenomenon is related to the alteration in the ferments of the skin that takes place during the transition period. Thus while the protease of the adult type of skin causes a definite autolysis, that of the fetal skin does not, the synthetic potential evidently predominating. Of greater significance seems to be the fact that the skin of the young animal contains peptidase to a considerable amount, while the adult skin seems to be without this ferment activity. If we assume that the disintegration of the native protein of the antigen is essential in eliciting certain skin tests, it would seem probable that the splitting would be less apt to take place in the young skin in which the lytic effects of the ferments are relatively suppressed. On the other hand, the young skin, containing peptidase, would be able to digest rapidly any antigen consisting of partially hydrolyzed proteins—as tuberculin—and in this way detoxicate and remove the noxious material. From these considerations the undoubted alteration of the skin reactivity taking place after infancy seems definitely correlated with changes in the proteolytic ferments. In how far they enter into and alter the specific reactions cannot be determined from the limited data so far available. Of the other ferments, the lipases, as pointed out by Porter, are possibly of importance in the resistance of the skin to tuberculous infection. It will be observed from the table that the activity of these skin ferments is less manifest in their action as esterases, on ethyl butyrate, than on the neutral fats used, oleic oil and butter fat, in this way differing from the activity of the serum. The relative resistance of the skin to tuberculous infection can, however, hardly be due to the activity of the lipase alone, for it must be kept in mind that the lepra bacillus, also rich in lipoids, is enabled to proliferate well within the epithelial tissues.     

Sex differences of human trabecular bone microstructure in aging are site-dependent.

In this study, we characterize bone microstructure, specifically sex differences, at multiple skeletal sites in 165 subjects >52 yr of age, using microCT technology in vitro. Significant sex differences are observed at the distal radius, femoral neck, and femoral trochanter, but not at the iliac crest, calcaneus, and lumbar vertebral body. Correlations in BV/TV between sites ranged from r = 0.13 to 0.56. INTRODUCTION: The goals of this study were (1) to assess potential sex differences of bone microstructure and their difference between skeletal sites and (2) to explore the relationship of trabecular microstructural properties between relevant skeletal sites. MATERIALS AND METHODS: Trabecular bone microstructural properties were measured in vitro in 165 subjects 52-99 yr of age using microCT. Defined volumes of interest (cylinders with 6 mm diameter and 6 mm length) were scanned at a resolution of 26 microm (isotropic) in six different anatomical sites: distal radius, femoral neck and trochanter, iliac crest, calcaneus, and second lumbar vertebral body. RESULTS: At the radius and femoral neck, trabecular bone displayed a more plate-like structure, thicker trabeculae, smaller separation/higher trabecular number, higher connectivity, and a higher degree of anisotropy in men than in women (p < 0.05). At the trochanter, men displayed more plate-like structure and thicker trabeculae (p < 0.05), but no differences in trabecular separation or other parameters compared with the women. At the calcaneus, iliac crest, and second lumbar vertebra none of the bone parameters displayed significant differences between sexes. The BV/TV at one site explained a range of only 2-32% of the variability at other sites. CONCLUSIONS: These results suggest that trabecular bone microstructural properties are remarkably heterogeneous throughout the skeleton. Significant differences between men and women are observed at some, but not at all, sites. The magnitude of sex differences in trabecular microstructure coincides with that of fracture incidence observed for some of the sites in epidemiological studies.     

Minimally Invasive Coracoclavicular Ligament Augmentation With a Flip Button/Polydioxanone Repair for Treatment of Total Acromioclavicular Joint Dislocation

Treatment of complete acromioclavicular joint disruption remains controversial and ranges from rehabilitation to extensive surgical reconstruction. However, high-grade injuries (type IV, V, and VI) are typically treated surgically. Most reconstruction techniques addressing these injuries selectively focus on coracoclavicular ligament augmentation because it has been shown to be the primary stabilizer of the acromioclavicular joint. The conventional coracoclavicular polydioxanone (PDS) loop, which is widely performed, has been detected to have some pivotal disadvantages, including anterior subluxation of the clavicle, extensive preparation of the coracoid, and bony avulsion of the clavicle as a result of rotational clavicle movement. Therefore we present an augmentation technique that reduces these complications by replicating the orientation of the native coracoclavicular ligament complex and providing a minimally invasive subcoracoid and clavicular fixation of a double PDS loop by use of 2 flip buttons, typically used for extracortical anterior cruciate ligament graft fixation. The key step of the procedure includes the anatomic, secure, and stable placement of the double PDS cerclage under the coracoid base transferring a flip button through a coracoid bone tunnel. Our clinical experience shows that the presented technique is easy to perform and has a comparable invasiveness to recently presented arthroscopic techniques.