Bulletin et memoires de l'Academie royale de medecine de Belgique最新文献

Female stress urinary incontinence (SUI) is mainly due to an excessive mobility of the cervico-urethral complex. Synthetic tapes placed without tension underneath the urethra to correct this hypermobility have revolutionized the surgical treatment of female SUI for the past fifteen years. The retropubic approach, namely the "tension-free vaginal tape" (TVT), was designed in 1996. It generates high SUI cure rates but is associated with a risk of intrapelvic bleeding and bladder and intestine perforation. The inside-out transobturator approach, which was developed eight years ago in our Institution, has since been used worldwide. The surgical technique is simple and reproducible and the incidence of peri- and post-operative complications is reduced. SUI cure rates are +/- 90% after a 3-5 years follow-up, similar to those obtained after the retropubic route. We have recently improved our original technique by using a shorter tape while, at the same time, minimizing the dissection required for its insertion. After a one year minimum follow-up, this new technique appears as safe and efficient as the traditional transobturator technique but is associated with reduced post-operative groin pain. We introduce for the first time the concept of the transobturator "midi sling".

The evolutionary origin of Man in the African continent has imposed the requirement to resist endemic parasites, in particular African trypanosomes (prototype: Trypanosoma brucei). Therefore, human serum is provided with an efficient system of innate immunity against these parasites, as discovered by A. Laveran in 1902. However, two T. brucei clones, termed T. b. rhodesiense and T. b. gambiense, managed to escape this immunity system, enabling them to grow in humans where they cause sleeping sickness. We have identified the gene allowing T. b. rhodesiense to resist trypanolysis by human serum, which led us to discover that the trypanolytic factor is apolipoprotein L1 (apoL1). ApoL1 is a human-specific serum protein bound to HDL particles that also contain another human-specific protein termed "haptoglobin-related protein " (Hpr). Following the binding of hemoglobin (Hb) to Hpr, the apoL1-bearing HDL particles are avidly taken up by the trypanosome through their binding to a parasite surface receptor for the Hp-Hb complex. After endocytosis apoL1 kills the parasite by generating anionic pores in the lysosomal membrane. In our laboratory, mutant versions of apoL1 have been constructed, which are no longer neutralized by the resistance protein of T. b. rhodesiense and are therefore able to kill this human pathogen. Unexpectedly, we have recently discovered that similar mutants do actually exist in nature : in Africans and Americans of recent African origin, even a single allele of these mutants allows protection against infection by T. b. rhodesiense, but the price to pay is a high frequency of end-stage renal disease when doubly allelic. The evidence of natural selection of these apoL1 mutations despite their deleterious potential for kidneys highlights the importance of the resistance to trypanosomes in the evolution of Man. The mechanism by which mutant apoL1 triggers end-stage renal disease is currently studied.

While the importance of airway inflammation in severe asthma was known from the pathologists for more than one century, the demonstration of an airway inflammatory process in mild asthma dates back to the early nineties. With the advent of bronchoscopy making it possible to sample biopsies and bronchoalveolar lavage, it has become clear that mild to moderate asthma was characterized by a Th2 driven airway eosinophilic inflammation where cytokine like IL-4, IL-5 and IL-13 play a critical role. Soon after, were developed the technique of induced sputum and the measurement of exhaled nitric oxide as non invasive tools to assess airway inflammation. The application of these techniques on large samples of subjects has been instrumental to the development of the concept of inflammatory phenotype in asthma which proved to be pertinent in the drug management of the disease. Therefore, within a 20 year laps, the monitoring of airway inflammation, also called inflammometry, has gone beyond the academic world to become crucial for the appropriate management of asthmatics by the clinician.

Asthma is one of the most common chronic diseases, affecting 5-10% of the population worldwide. It is closely associated with the "atopic" hypersensitivity to environmental antigens ('allergens'), which is mediated by specific IgE driven by a T helper 2-type immune response, also promoting recruitment of eosinophils and mast cells and mucus overproduction. Our first research axis showed that allergen immunotherapy in patients with allergic rhinitis and asthma to grass pollen induces inhibition of the IL-9/ mast cells axis and a selective induction of allergen-specific IgA2 antibodies in serum, which correlated to nasal tissue expression of TGF-beta. We further showed that these IgA antibodies, whilst unable to inhibit IgE-facilitated allergen presentation by B cells as achieved by IgG4 antibodies, could trigger IL-10 expression in monocytes and dendritic cells through activation of p38 MAP-kinase and recruitment of sp1 and NFkappaB transcription factors. In addition, results in a murine model of asthma suggested a protective role of secretory IgA. A second research axis, exploring local immune responses to lung allergen exposure, identified the CCR4 pathway as critically mediating the recruitment of Th2 cells into the lung of atopic asthmatics. In patients with non-atopic (intrinsic) asthma, we recently reported on the local production of specific IgE to mite allergens (Der p), able to activate basophils in vitro, while lung challenge to Der p in vivo did not result into asthmatic responses. Altogether, we showed (1) that allergen immunotherapy triggers production of IgA2, which could be protective through induction of IL-10 in monocytes/dendritic cells and/ or by scavenging allergens within secretions, and (2) that allergen exposure, which triggers the recruitment of Th2 cells through the CCR4 pathway, induces locally the production of specific IgE, irrespectively of systemic atopic features, supporting the concept according which "second signals" condition in vivo the inception and exacerbations of asthma.

Although very effective, some drugs have considerable side effects and are characterized by a relatively narrow therapeutic index. It is therefore sometimes required to regularly check their blood concentration in order to find the best compromise between optimal therapeutic efficacy and reduced toxicity. A therapeutic drug monitoring (TDM) is applied for immunosuppressants used in solid organ transplantation and for antiretrovirals used in the treatment of HIV infections. A first improvement of conventional TDM consists in trying to understand the origin of the inter-individual variability at the pharmacokinetic level in order to anticipate it and to propose individualized dose adjustment according to each patient's genetic characteristics. A complementary improvement consists in measuring the active biological dose of the drug directly in target tissues (lymphocytes for both pharmacological classes considered) and in studying genetic and other factors, influencing this parameter. In complement to conventional TDM, pharmacogenetics therefore allows a better individualization of drug therapy.

A first reason for the psychiatrist to be interested in music, musicians and their artistic work, comes from the strong biographical and scientific evidence linking mood disorders and in particular, bipolar disorder, to artistic creativity. Moreover, a family association between psychopathology and creativity has been found in several studies. Important changes in mood, but also cognition, personality and behaviour can occur during all phases of manic-depressive illness and these changes have potentially important effects on creativity and productivity. Those changes are usually opposite in mania and depression. Many bipolar artists see emotional turmoil as essential to their creativity, which has therapeutical but also ethical consequences. A second area of interest is the impaired emotional recognition in schizophrenic patients, not only for visual material (faces or contextual scenes) but also for auditive material (voice or music) leading to impaired social interactions in this condition.

Reconstruction of long-segment tracheal defects requires a vascularized allograft. We report successful tracheal allotransplantation after indirect revascularization of the graft in a heterotopic position. Immunosuppressive therapy was administered before the operation, and the allograft was wrapped in the recipient's forearm fascia. Once revascularization was achieved, the mucosal lining was replaced progressively with buccal mucosa from the recipient. At four months, the tracheal chimera was fully lined with mucosa, which consisted of respiratory epithelium from the donor and buccal mucosa from the recipient. After withdrawal of immunosuppressive therapy, the tracheal allograft was moved to its correct anatomical position with an intact blood supply. No treatment-limiting adverse effects occurred.

Since the first successful liver transplantation (LT) in 1963 by Starzl, enormous progresses have been made in this field of medicine. The author looks back at the recommendations put forward at the 1983 NIH Consensus conference on liver transplantation in order to show the enormous progresses that have been made in his field during the last four decades. Today almost none of the original indications and contraindications remain in place. Despite the extension of indications, results of LT continuously improved. The attention of the transplant physicians should from now onwards be focused on the achievement of an immunosuppressive free (or tolerant) status in order to further consolidate the excellent obtained long-term results.

The place of bone allograft in contemporary orthopaedic surgery is discussed. Bone allograft can be prepared from retrieved femoral heads for fracture or osteoarthritis and are used as a filling material. Demineralized bone matrix is a cortical bone that has been exposed to a demineralizing solution. Doing so, the growth factors of the bone are exposed and will be able to induce the formation of new bone cells from the host. This osteoinductive capacity makes the graft more active in the process of its incorporation and has been successfully used in the conservative treatment of aneurismal bone cysts. Massive bone allografts can be used as a full segment of a long bone to reconstruct part of the skeleton either alone with fixation or with a prosthetic device. Except demineralized bone, any other types of bone allograft serve as a biologic passive support for the migrating cells from the host. Cellular therapy is another approach that allows, considering the extensive use of in vitro expanded bone, forming cells originating either from the bone marrow or the fat tissue of the patient. However, this approach needs further clinical validation before being fully considered in patient.