Original Koyanagi urethroplasty versus modified Hayashi technique: Outcome in 57 patients

ObjectiveTo compare outcomes of the original Koyanagi technique with the Hayashi modification in severe hypospadias, i.e. hypospadias with a division of the corpus spongiosum located behind the penile midshaft associated with marked hypoplasia of the ventral aspect of the penis and a non-preservable urethral plate. Choice of technique for treating severe hypospadias is discussed.Patients and methodsTwenty-six patients (group I) were operated in Lyon using the original Koyanagi procedure and 31 (group II) underwent a modified Hayashi procedure in Paris. Most patients received preoperative androgenic stimulation. Mean follow up was 25 months (group I) and 34 months (group II).ResultsSixteen patients (61.5%) in group I and 19 (61.3%) in group II developed complications leading to 21 additional procedures in each group. Urethral dehiscence was found in 11/26 patients in group I (42.3%), and in 6/31 patients in group II (19.3%); fistulae were respectively found in 5/26 (19.2%) and 12/31 (38.7%), and stenosis in 9/26 (34.6%) and 5/31 (16.1%) patients. Urethrocele was found in 7/26 (26.9%) and 5/31 (16%) patients, respectively. Twelve (group I) and 7 (group II) patients are awaiting re-operation.ConclusionAlthough the complication rate is quite similar between the original and the modified Koyanagi procedure, the Hayashi technique seems to provide a better distal blood supply to the reconstructed urethra.     

La greffe spongieuse appuyée sur le péroné (GSAP) dans le traitement des fractures ouvertes type III

An alternative to the preceding treatments is to put cancellous graft onto the fibula (14 cases). The first stage is excision and fixation by external fixator and the second stage is filling the tibial/fibula interspace with cancellous graft. The indications for this technique are limited by the quantity of cancellous bone available in the iliac crests and thus a fairly short bony defect, the presence of skin loss over the bony defect and the absence of major vascular lesions. In spite of not using flaps for skin cover healing occurred on average 7.9 months after carrying out several repeated bone grafts and skin grafting.     

Spread of a Klebsiella pneumoniae strain producing a plasmid-mediated ACC-1 AmpC beta-lactamase in a teaching hospital admitting disabled patients

We describe a large outbreak involving a Klebsiella pneumoniae strain producing a plasmid-encoded ACC-1 type AmpC beta-lactamase in a hospital caring for patients with motor impairment. The epidemic strain was isolated from 57 patients in six wards between September 1999 and May 2003 and caused clinical infections in 19 patients.     

Glycosaminoglycans and protein disulfide isomerase-mediated reduction of HIV Env

Conformational changes within the human immunodeficiency virus-1 (HIV-1) surface glycoprotein gp120 result from binding to the lymphocyte surface receptors and trigger gp41-mediated virus/cell membrane fusion. The triggering of fusion requires cleavage of two of the nine disulfide bonds of gp120 by a cell-surface protein disulfide-isomerase (PDI). Soluble glycosaminoglycans such as heparin and heparan sulfate bind gp120 via V3 and, possibly, a CD4-induced domain. They exert anti-HIV activity by interfering with the HIV envelope glycoprotein (Env)/cell-surface interaction. Env also binds cell-surface glycosaminoglycans. Here, using surface plasmon resonance, we observed an inverse relationship between heparin binding by gp120 and its thiol content. In vitro, and in conditions in which gp120 could bind CD4, heparin and heparan sulfate reduced PDI-mediated gp120 reduction by approximately 80%. Interaction of Env with the surface of lymphocytes treated using sodium chlorate, an inhibitor of glycosaminoglycan synthesis, led to gp120 reduction. We conclude that besides their capacity to block Env/cell interaction, soluble glycosaminoglycans can effect anti-HIV activity via interference with PDI-mediated gp120 reduction. In contrast, their presence at the cell surface is dispensable for Env reduction during the course of interaction with the lymphocyte surface. This work suggests that the reduction of exofacial proteins in various diseases can be inhibited by compounds targeting the substrates (not by targeting PDI, as is usually done), and that glycosaminoglycans that primarily protect proteins by preserving them from proteolysis also have a role in preventing reduction.     

Idiopathic male pseudohermaphroditism: variations in presentation and management

Male pseudohermaphroditism (MPH) is the abnormal development of genitalia in an individual with a 46,XY chromosome complement and testicular tissue. The etiology of MPH is unknown in most cases, which are defined as idiopathic. OBJECTIVE: To analyze the data for cases of idiopathic MPH. PATIENTS AND METHODS: A retrospective study of 29 patients with idiopathic MPH and no uterus. Results: Four patients had a family history of abnormal sexual development and five had low birth weight. The initial manifestations were sexual ambiguity (26), microphallus and hypospadias (2), and primary amenorrhea (1). Basal and/or stimulated testosterone concentrations showed insufficient testosterone secretion in three patients. Genitography showed a vagina in 13 patients. Male genitoplasties were performed on 21 out of the 24 patients reared as males and female genitoplasties on five patients. Histological studies of the gonads of these showed streak gonads in one, normal gonads in one and signs of testicular dysgenesis in three others. Molecular studies on the SRY gene (17) showed no mutation. CONCLUSIONS: Idiopathic male pseudohermaphroditism is a heterogeneous condition, even within families with a history of this condition. We propose a set of guidelines for the management of these patients.     

Heparan sulfate proteoglycan mediates the selective attachment and internalization of serotype 3 human adenovirus dodecahedron

During adenovirus type 3 (Ad3) infection cycle, the penton (Pt) of the viral capsid, a noncovalent complex of fiber and penton base proteins, is produced in large excess and self-assembles to form a highly organized dodecahedral structure, termed dodecahedron (Dd). The physiological role of these particles is poorly understood, but we have recently reported that they can penetrate cells with high efficiency and thus may constitute an attractive tool for gene or protein delivery approaches. Surprisingly, Dd displayed the ability to enter cells non-permissive to Ad3, suggesting the existence of additional internalization modes. In this study, we show that Ad3 Dd binds to cell surface heparan sulfate (HS) through high affinity interaction with the penton base. Furthermore, binding to HS was found to be the prerequisite for a novel and Dd specific entry pathway that could not be used by Ad3. Overall, these data provide new insights in the possible role of Dd during viral infection and potential therapeutic applications.     

Heparan sulfate-mediated binding of infectious dengue virus type 2 and yellow fever virus

Dengue virus type 2 and Yellow fever virus are arthropod-borne flaviviruses causing hemorrhagic fever in humans. Identification of virus receptors is important in understanding flavivirus pathogenesis. The aim of this work was to study the role of cellular heparan sulfate in the adsorption of infectious Yellow fever and Dengue type 2 viruses. Virus attachment was assessed by adsorbing virus to cells, washing unbound virus away, releasing cell-bound virus by freezing/thawing, and then titrating the released infectious virus. Treatment of cells by heparin-lyase, desulfation of cellular heparan sulfate, or treatment of the virus with heparin inhibited cell binding of both viruses. Heparin also inhibited Yellow fever virus infection by 97%. Using infectious virus, the present work shows the importance of heparan sulfate in binding and infection of these two flaviviruses.     

Foxl-2 in gonad development and pathology

The Foxl-2 gene is involved in eyelid and ovary development. Mutations can lead to a shortened protein and malformations such as BPES associated or not to POF. Forkhead point mutation C134W is a marker of adult type granulosa cell tumors only. Foxl-2 dysregulation is also present in DSD and DSD associated tumors such as Gonadoblastoma and gonadoblastoma like intratubular undetermined germ cell neoplasia. A similar spectrum of pathology involvement is also found for WT1 and RET and gives a new insight into the relationship between development, malformations and oncogenesis.