Mediolateral hoof balance in relation to the handedness of apprentice farriers.

Horses that had been trimmed and shod by apprentice farriers were sourced from the Royal School of Military Engineering, Melton Mowbray (37 horses) and from the Household Cavalry, Knightsbridge (54 horses). The lateral and medial hoof wall angles of both forelimbs were measured using a Ruidoso hoof gauge by the same operator. The difference between the lateral and medial hoof wall angles for each horse was calculated and the results were compared between right-handed and left-handed farriers using the Mann-Whitney U test (P<0.05). There was a significant difference in the mediolateral hoof balance obtained between right-handed and left-handed farriers for each forelimb (P<0.001). Right-handed farriers were shown to create an imbalance in 47 per cent of left forelimbs and 46 per cent of right forelimbs assessed, while left-handed farriers created an imbalance in 41 per cent of left forelimbs and 71 per cent of right forelimbs. The tendency was for right-handed farriers to over-trim the medial (inner) aspect of the left forelimb and the lateral (outer) aspect of the right forelimb; the reverse was demonstrated for left-handed farriers. Performing a risk ratio confirmed these findings.

Relevance of the tumor antigen in the validation of three vaccination strategies for melanoma.

Many preclinical studies of cancer immunotherapy are based on the testing of a single vaccination strategy in several tumor models. Moreover, most of those studies used xenogeneic Ags, which, owing to their high immunogenicity, may not represent realistic models for the validation of cancer immunotherapies. To address these issues, we compared the vaccination efficacy of three well established strategies (i.e., naked DNA; peptide-pulsed dendritic cells (DC), or a mixture of peptide and the Escherichia coli toxin LTR72) using the xenogeneic OVA or the naturally expressed tyrosinase-related protein 2 (TRP-2) tumor Ag in the B16 melanoma model. C57BL/6 mice received one to three s.c. injections of peptide-pulsed DC or DNA, or one to four mucosal administrations of peptide-toxin mixture. One to 2 wk later, the animals were challenged s.c. with B16 or B16 cells expressing OVA (B16-OVA). Vaccination of mice with OVA induced in all cases melanoma-specific CTL and protection against B16-OVA. When TRP-2 was used, all three vaccines elicited B16-specific CTL, but only DC pulsed with the immunodominant T cell epitope TRP-2181-188 allowed protection against B16. Even more importantly, a vaccination regimen with TRP-2-pulsed DC, started 24 h after the injection of a lethal number of B16 cells, caused a therapeutic effect in 60% of the challenged animals. Our results strongly emphasize the relevance of the tumor Ag in the definition of immunotherapeutic strategies for cancer, and support the use of peptide-pulsed DC as cancer vaccine in humans.

[Multicenter study on the effectiveness of Tension Vaginal Tape (TVT) in the treatment of stress urinary incontinence]. / Studio multicentrico sull'efficacia del Tension Free Vaginal Tape (TVT) nella terapia della incontinenza urinaria da sforzo.

BACKGROUND: The aim of the study was to evaluate the efficacy of Tension Free Vaginal Tape (TVT) for the surgical treatment of stress urinary incontinence. METHODS: The design was an open multicenter study including six Italian hospitals. Between January 1998 and November 1999, 429 stress incontinent women were enrolled in the study. Before surgery subjects had been studied through their history, urine culture, physical examination, cotton swab test, cough provocation test and urodynamic evaluation including: uroflowmetry, water cystometry and urethral profilometry. Incontinence inconvenience has been quantified through a 10-grade visual analogue scale (VAS). Postoperatively patients were assessed after 6, 12 and 24 months. RESULTS: The mean age of the patients considered was 57 years (range 31-83) and 78 of them had undergone a previous operation for the treatment of stress urinary incontinence or genital prolapse. Out of the 429 patients, 371 were followed for a minimum of 6 months, 11 were lost to follow-up and 47 had been operated recently. After surgery 355 subjects (96%) were subjectively cured and no leakage of urine was observed in 97% of the patients during the postoperative cough provocation test. CONCLUSIONS: This study carried out on a great number of patients demonstrates that TVT is a safe and effective procedure for the treatment of stress urinary incontinence.

Role of antigen-presenting cells in cross-priming of cytotoxic T lymphocytes by apoptotic cells.

Although the mechanisms regulating recognition and phagocytosis of apoptotic cells by scavenger cells are the subject of intense investigation, little is known about the fate of the antigens contained in apoptotic cells and the constraints defining their immunogenicity. We developed a model in C57BL/6 mice to evaluate whether phagocytosis of apoptotic tumor cells yielded antigens able to get access to the MHC class I pathway and activate a specific cytotoxic T lymphocyte response. Our results demonstrate that apoptotic tumor cells are antigenic in vitro and can be immunogenic in vivo. Their immunogenicity depends on the number of cells used for immunization and the antigen-presenting cells involved in processing and presentation of antigens contained in the dying cells. The demonstration of the immunogenicity of apoptotic cells may have direct implications both in autoimmunity and cancer.

Immunogenicity of apoptotic cells in vivo: role of antigen load, antigen-presenting cells, and cytokines.

Apoptosis allows the clearance of unwanted cells from living tissues without causing inflammation. Processing of phagocytosed apoptotic cells yields Ags that access the cytosol and the MHC class I pathway of engulfing cells and are recognized by Ag-specific CTL. We show here that injection of apoptotic RMA cells, a syngeneic T cell lymphoma, into C57BL/6 mice results in priming of a functional and long-lasting tumor-specific immune response. Cross-priming of CTLs by apoptotic cells requires CD4+ T cell help. Apoptotic cells, however, are at least 20-fold less immunogenic than nonreplicating live cells. Immunogenicity of apoptotic cells is proportional to the number of cells injected, correlates with the serum concentration of IL-10 and IL-1beta cytokines, and is enhanced in IL-10 knockout mice. Moreover, immunization with dendritic cells (DCs), but not macrophages (Mphi), pulsed with apoptotic cells primes tumor-specific CTLs and confers protection against a tumor challenge. Our findings demonstrate that tumor cells undergoing apoptosis are, though scarcely, immunogenic in vivo, outline the different roles of Mphi and DCs in the physiologic clearance of unwanted cells, and have implications in designing immunomodulating vaccines.

The immunogenicity of experimental tumors is strongly biased by the expression of dominant viral cytotoxic T-lymphocyte epitopes.

The immunogenic Friend-Moloney-Rauscher (FMR) virus-induced tumors have been used extensively to clarify the cellular and molecular mechanisms responsible for tumor rejection and to develop immunotherapeutic strategies. We characterize here the trimolecular complex MHC class I-antigenic determinant-T cell receptor involved in the induction of a protective CTL response against the RMA thymoma. This complex is mainly composed by the D(b) molecule interacting with a Rauscher virus antigen (Ag) determinant and the Vbeta5+ T cell receptor. We also show that the chemically induced EL-4 thymoma acquires the susceptibility to recognition by anti-RMA CTLs and the ability to elicit a protective anti-RMA CTL response only upon infection by a virus of the FMR family and that RMA and FMR virus infected EL-4 cells share tumor-associated Ag. The data strongly support the hypothesis that the high immunogenicity of virus-induced or infected tumors is determined by the expression of immunodominant virus-encoded Ag. The demonstration of a different outcome in the immune responses elicited in the presence or in the absence of viral Ag further open the contention of the molecular requirements for immunogenicity and should stimulate a more careful revision of unexpected cross-reactivity among tumors.

Processing of engulfed apoptotic bodies yields T cell epitopes.

Programmed death via apoptosis is the metazoan physiologic mode of cell death. Apoptotic cells are recognized by scavenger phagocytes via a number of membrane receptors and engulfed. Thereafter, little is known of their fate, or that of phagocytes. Here, we have traced apoptotic cells upon their engulfment by macrophages. After 3 h, apoptotic cells were contained in discrete well-defined vacuoles. Upon overnight chase, several small vesicles, possibly originating from the fragmentation of original vacuoles, were evident all over the macrophage body. Furthermore, Ags were diffused in the cytosol of some cells, which raises the possibility that epitopes from engulfed apoptotic cells may associate with macrophage MHC class I molecules and be recognized by T lymphocytes. Indeed, Ag-specific CTLs recognize and specifically lyse syngeneic macrophages upon phagocytosis of MHC class I-positive or -negative apoptotic cells, provided that they contain the relevant Ags. Synthesis and membrane expression of class I molecules by macrophages, together with functional transporters associated with Ag presentation, were necessary for recognition and lysis. The indirect presentation of epitopes from engulfed apoptotic cells by scavenger Ag-presenting phagocytes may, in the absence of "danger" signals, have implications for the establishment of central and peripheral self-tolerance.

[FDDF (fast dissolving dosage form) piroxicam for sublingual administration in the treatment of rheumatoid arthritis]. / Il piroxicam FDDF per via sublinguale nel trattamento dell'artrite reumatoide.

Open non-comparative study for the evaluation of the efficacy and tolerance of piroxicam FDDF for sublingual administration in the treatment of rheumatoid arthritis. Thirty patients (6 males and 24 females) suffering from rheumatoid arthritis in the active phase have been treated. All the patients had to fulfil the criteria for the rheumatoid arthritis classification proposed by the American Rheumatism Association (ARA). The efficacy of therapy has been evaluated, after 2, 4 and 6 week of treatment, through the changes in: the number of painful or tender joints on motion, the number of swollen joints, grip strength, ESR. Also day pain, night pain, duration of morning stiffness and functional index have been evaluated. As regards the functional index, activities as dressing, arising, eating, walking, taking care of hygiene, bending, standing and sitting have been considered. The study sample was composed by 30 patients, with a mean age of 59.73 years, suffering from rheumatoid arthritis from 4.76 years. As regards efficacy parameters, day pain, which is recorded on a 21 compartment visual analogue scale, was initially of 8.13 (+/- 3.73), and after 2 weeks of therapy decreased of about 1 point and after 4 weeks was of 6.57 (+/- 3.73). This improvement was already statistically significant at the first control (p = 0.01). At the first control also morning stiffness resulted improved in a statistically significant way (p < 0.0001). As regards functional index a statistically significant improvement was observed in the disability of walking and of picking up objects after 2 weeks; after 4 weeks a significant improvement was observed in the disability of arising and of bending. These changes in functional ability probably depend upon the kind of joint involved and the duration of these lesions. Also the grip strength resulted statistically improved at the 2 control. As regards objective values, there was a statistically significant improvement in tender and swollen joints after only 2 weeks. As regards ESR, which is an index of disease activity, was initially of 40.73 (+/- 16.75) in mean; at the end of the 6th week it was of 34.72 (+/- 15.13): this reduction was statistically significant. No improvement was observed in night pain, normally the pain form which is more difficult to cure. As regards toleration, only 2 patients reported side-effects: the first reported epigastralgia and the second oral burning Both side-effects lasted 1 day and, according to the physician, their relation with the study drug is not sure.(ABSTRACT TRUNCATED AT 400 WORDS)

Frequency and clinical significance of anti-RNP antibodies in Italian SLE patients.

The frequency and clinical significance of anti-RNP antibodies in patients with systemic lupus erythematosus (SLE) are still a matter of debate. In this study we report our experience with a series of 123 unselected Italian patients (93 adults and 30 children) suffering from SLE according to the ARA criteria. Anti-RNP were detected by counterimmunoelectrophoresis in 25 patients (20%), 19 of whom did not show other antibodies to extractable antigens (isolated RNP). Our study shows a striking association between anti-RNP and arthritis as well as between anti-RNP and Raynaud's phenomenon. In addition, we found an association between anti-RNP and lack of renal involvement. This association was limited to those patients with isolated RNP and was independent of the presence of anti-dsDNA antibodies. These data were confirmed by a 50 month follow-up study.