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Biomedical subjects

Gérard Benoit

Publications and source records attributed to Gérard Benoit.

At least 19 recordsLinked to original sources
PubMed2006

Candida albicans arteritis transmitted by conservative liquid after renal transplantation: a report of four cases and review of the literature.

BACKGROUND: Mycotic arteritis and/or aneurysms are infrequent complications of renal transplantation. They are mostly secondary to bacterial infection and rarely to Candida albicans. We report four cases of mycotic arteritis due to C. albicans after renal transplantation but which have been inoculated during organ harvesting or conservation. METHODS: In all the four cases corresponding to two independent donors, C. albicans was isolated few days later in the systematic culture of the conservative liquid. We also review the clinical features and outcomes of 13 cases previously reported in the literature. RESULTS: In two cases, the diagnosis of fungal arteritis was confirmed only during autopsy after the patient's death due to massive bleeding. In the other two cases, the diagnosis was made on the arterial section of the anastomotic wall after detransplantation for massive bleeding for arterial leakage although an immediate antifungal treatment with fluconazole and caspofungin was given and was found to be inefficient. CONCLUSION: This is a serious complication of renal transplantation because it leads to graft loss in the majority of the cases and even to death in a few cases despite an efficient and rapid treatment. Routine fungal cultures of preservation media are important for early diagnosis and timely surgical interventions are life-saving.

Adult↗
PubMed2006

Effects of potassium channel modulators on human detrusor smooth muscle myogenic phasic contractile activity: potential therapeutic targets for overactive bladder.

OBJECTIVES: Increased urinary bladder detrusor smooth muscle phasic contractility has been suggested to be associated with idiopathic bladder overactivity (OAB). We examined the role of voltage-dependent L-type calcium channels, adenosine triphosphate-sensitive potassium (K(ATP)) channels, and calcium-activated potassium (BK(Ca) and SK(Ca)) channels in the regulation of human detrusor phasic contractile activity. METHODS: Isolated human bladder strip phasic contractions were measured and quantified as the mean area under the force-time curve, amplitude, and frequency of phasic contractions in 22 bladder samples. RESULTS: Human detrusor strips displayed myogenic phasic contractions in the presence of atropine (10(-6) M), phentolamine (10(-6) M), propranolol (10(-6) M), suramin (10(-5) M), and tetrodotoxin (10(-6) M). The L-type calcium channel inhibitor nifedipine (300 nM) abolished the contractile activity. Blockade of K(ATP) channels by glibenclamide (1 and 10 microM) did not alter myogenic contractions. In contrast, the K(ATP) channel opener pinacidil (10 microM) markedly inhibited phasic contractility. Iberiotoxin (100 nM) and apamin (100 nM), potent and selective inhibitors of BK(Ca) and SK(Ca) channels, respectively, significantly increased the area under the force-time curve and the amplitude of contractions. CONCLUSIONS: Phasic contractions of human detrusor are dependent on calcium entry through L-type calcium channels. BK(Ca) and SK(Ca) channels play a key role in the modulation of human detrusor smooth muscle phasic contractility. Furthermore, these observations support the concept that increasing conductance through K(ATP), BK(Ca), and SK(Ca) channels may represent attractive pharmacologic targets for decreasing phasic contractions of detrusor smooth muscle in OAB.

Calcium Channels, L-Type↗
PubMed2006

Consequences of iliac arterial atheroma on renal transplantation.

PURPOSE: Because recipient age has significantly increased in the last 15 years, surgeons must sometimes deal with atherosclerotic lesions of the iliac arterial system. Arterial restoration during renal transplantation should now be less frequent due to better preoperative screening and the prevention of arteriosclerosis in patients on renal transplantation waiting lists but in some patients EIA atheroma may require an additional surgical vascular procedure during renal transplantation. We describe the role of iliac artery atherosclerosis and the technical aspects of arterial restoration performed in patients who have undergone renal transplantation since 1985. MATERIALS AND METHODS: In a series of 1,110 cadaveric renal transplantations performed between 1985 and 2000, 38 patients required endarterectomy during renal transplantation and 69 were considered not to require any special procedure. RESULTS: In the 38 patients requiring endarterectomy a total of 12 end-to-end arterial anastomoses were performed and 6 ASs (50%) were observed, while 26 side-to-end arterial anastomoses were performed with only 1 AS (4%). Patient and graft survival curves showed a significant negative correlation with the severity of atherosclerosis. CONCLUSIONS: Preoperative assessment of the EIA is mandatory before renal transplantation. Renal transplantation can be performed in patients with an atheromatous EIA if the artery can be clamped for endarterectomy. In our experience side-to-end anastomosis using a donor patch onto the EIA provides better results by avoiding AS after endarterectomy. However, despite vascular repair graft survival is significantly lower in patients with atheromatous lesions requiring endarterectomy.

Adult↗
PubMed2006

International Union of Pharmacology. LXVI. Orphan nuclear receptors.

Half of the members of the nuclear receptors superfamily are so-called "orphan" receptors because the identity of their ligand, if any, is unknown. Because of their important biological roles, the study of orphan receptors has attracted much attention recently and has resulted in rapid advances that have helped in the discovery of novel signaling pathways. In this review we present the main features of orphan receptors, discuss the structure of their ligand-binding domains and their biological functions. The paradoxical existence of a pharmacology of orphan receptors, a rapidly growing and innovative field, is highlighted.

Animals↗
PubMed2006

Expression of epidermal growth factor receptor and proliferative activity of cyst epithelium in human renal cystic diseases.

Pathogenesis of malignancies in patients with polycystic kidney disease (PKD) is not clearly understood. Epidermal growth factor receptor (EGF-r) production by mature kidney plays a role in promotion of epithelial hyperplasia and cyst formation, its involvement in further progression is however not proven. Ki-67 is a marker for cellular proliferation. We assessed immunohistochemical expression of EGF-r and Ki-67 in epithelium of normal kidney, single cysts without PKD, epithelial tubular cells lining simple cysts and cysts with papillary proliferation in PKD patients, and analyzed the relationship with the occurrence of malignant tumors in these cases. 72% of PKD displayed EGF-r staining in epithelium lining cysts versus 33% in normal epithelium and 70% in epithelium of normal kidney. Ki-67 was increased in papillary cystic epithelium (24%) and in cysts lined by flat epithelium (66%). Renal cancers in PKD showed EGF-r staining in 33%, but no Ki-67 expression. EGF-r function and proliferative activity in cyst formation in PKD remains to be explored. EGF-r and Ki-67 expressions are not predictive of development of carcinoma in PKD.

Adult↗
PubMed2006

[A case of ureteroduodenal fistula].

Ureteroduodenal fistulas are rare. The authors present a review of this disease in the light of a clinical case and emphasize the role of conservative management.

Duodenal Diseases↗
PubMed2005

Identification of androgen receptors in the motoneurons of the external urethral sphincter in the spinal cord of female rats.

OBJECTIVES: In women, aging is associated with profound hormonal changes. Menopause has been implicated in the etiology of urinary tract complaints including incontinence, urgency and recurrent urinary tract infections. However, the use of hormone replacement therapy for these conditions has given conflicting and disappointing results. The role of androgen changes on urinary continence in perimenopausal women has not been studied. We studied the presence of androgen receptors in pudendal motoneurons controlling the external urethral sphincter of female rats. MATERIALS AND METHODS: A combination of retrograde labeling of pudendal motoneurons from the external urethral sphincter and immunohistochemistry for the N-terminal portion of androgen receptors on spinal cord sections was performed in adult female rats. RESULTS: Androgen receptors were identified in the nuclei of the ventral horn of the L5-L6 spinal cord. Pudendal motoneurons, retrogradely labeled from the external urethral sphincter, were identified in the dorsolateral nucleus of the ventral horn at the same levels. Confocal microscopy demonstrated the presence of nuclear and cytoplasmic androgen receptors in the cell bodies of these retrogradely labeled pudendal motoneurons. CONCLUSION: Our study demonstrated the presence of androgen receptors in the cell bodies of retrogradely labeled pudendal motoneurons controlling the urethral sphincter of female rats suggesting a role of androgens in the neuromodulation of urethral sphincter function at the spinal level.

Animals↗
PubMed2005

Morphological study of the spinal motoneurons controlling the urethral sphincter of female rats: role of androgens in a menopausal model.

PURPOSE: In this study in a menopausal rat model we describe the effect of androgen withdrawal on motoneurons innervating 2 muscles involved in female urinary continence, namely the intrinsic urethral sphincter and the pubococcygeus muscle. MATERIALS AND METHODS: The 5 groups studied were 2 ovariectomized groups and their sham operated controls plus 1 ovariectomized group with dihydrotestosterone supplementation. Blood testosterone assays were performed. Androgen receptor immunohistochemistry was performed on spinal cord sections, in which specific motoneuron subpopulations were identified. Maximal somal cross-sectional area was compared among the groups. RESULTS: Differences in somal cross-sectional area of motoneurons innervating the pubococcygeus muscle were observed after ovariectomy. Androgen receptor immunopositive nuclei staining disappeared, in line with undetectable blood testosterone levels. DISCUSSION: The modifications of androgen receptor expression and somal morphological appearance in the pudendal motoneurons controlling the external urethral sphincter of ovariectomized female rats suggests that testosterone probably influences neurotransmission and coordination of urinary continence at the spinal level.

Androgens↗
PubMed2004

Defining an N-terminal activation domain of the orphan nuclear receptor Nurr1.

Nurr1 is an orphan nuclear receptor essential for the development of midbrain dopaminergic neurons. Activation of Nurr1 depends on two so-called activation functions (AFs) situated in the N- and C-terminal regions, respectively. The region important for activation within the C-terminal domain has been shown to promote activation in a highly cell-type specific fashion in the absence of added exogenous ligands. In contrast, the region in the N-terminal domain (AF1) has been much less characterized. Here we mutagenized the N-terminal domain of Nurr1 to define essential activation regions. The results identified a short core activation region localized close to the N-terminus of Nurr1. In addition, cell-type specific influences by other signaling pathways were analyzed by mutagenesis of specific conserved phosphorylation sites. The results indicate that mitogen-activated protein kinase activity (MAPK) positively influences Nurr1 AF1-dependent transcriptional activation via a conserved phosphorylation site outside the core activation region.

Amino Acid Sequence↗
PubMed2004

Digging deep into the pockets of orphan nuclear receptors: insights from structural studies.

Nuclear receptors comprise a large family of proteins that shares a common structure and mechanism of action. Members of this family, first cloned 20 years ago, are regulated by small lipophilic signaling molecules such as steroid hormones, retinoids and thyroid hormone. More recently, the characterization of proteins that resemble nuclear receptors (referred to as orphan receptors) has resulted in the determination of novel signaling pathways. However, many orphan-receptor ligands remain unidentified, and recent structural studies of the binding domains for orphan-receptor ligands suggest that not all of these receptors use ligand binding in a classical way. Notably, it is now evident that some orphan receptors lack the capacity for ligand binding, which suggests that they are regulated by alternative, ligand-independent mechanisms.

Animals↗
PubMed2004

[Scrotal angiofibroblastoma].

Angiomyofibroblastoma of the scrotum is a rare and benign tumour which affect old patient. It's treatment is surgical. A case of angiomyofibroblastoma of the scrotum is reported in a 34 years old man. The literature is reviewed with special reference to the ethiopathogenesis, clinical features and treatment of this tumour entity.

Adult↗
PubMed2003

p57(Kip2) cooperates with Nurr1 in developing dopamine cells.

Cyclin-dependent kinase inhibitors of the Cip/Kip family play critical roles in regulating cell proliferation during embryogenesis. However, these proteins also influence cell differentiation by mechanisms that have remained unknown. Here we show that p57Kip2 is expressed in postmitotic differentiating midbrain dopamine cells. Induction of p57Kip2 expression depends on Nurr1, an orphan nuclear receptor that is essential for dopamine neuron development. Moreover, analyses of p57Kip2 gene-targeted mice revealed that p57Kip2 is required for the maturation of midbrain dopamine neuronal cells. Additional experiments in a dopaminergic cell line demonstrated that p57Kip2 can promote maturation by a mechanism that does not require p57Kip2-mediated inhibition of cyclin-dependent kinases. Instead, evidence indicates that p57Kip2 functions by a direct protein-protein interaction with Nurr1. Thus, in addition to its established function in control of proliferation, these results reveal a mechanism whereby p57Kip2 influences postmitotic differentiation of dopamine neurons.

Animals↗
PubMed2003

Structure and function of Nurr1 identifies a class of ligand-independent nuclear receptors.

Members of the nuclear receptor (NR) superfamily of transcription factors modulate gene transcription in response to small lipophilic molecules. Transcriptional activity is regulated by ligands binding to the carboxy-terminal ligand-binding domains (LBDs) of cognate NRs. A subgroup of NRs referred to as 'orphan receptors' lack identified ligands, however, raising issues about the function of their LBDs. Here we report the crystal structure of the LBD of the orphan receptor Nurr1 at 2.2 A resolution. The Nurr1 LBD adopts a canonical protein fold resembling that of agonist-bound, transcriptionally active LBDs in NRs, but the structure has two distinctive features. First, the Nurr1 LBD contains no cavity as a result of the tight packing of side chains from several bulky hydrophobic residues in the region normally occupied by ligands. Second, Nurr1 lacks a 'classical' binding site for coactivators. Despite these differences, the Nurr1 LBD can be regulated in mammalian cells. Notably, transcriptional activity is correlated with the Nurr1 LBD adopting a more stable conformation. Our findings highlight a unique structural class of NRs and define a model for ligand-independent NR function.

Binding Sites↗
PubMed2003

Diagnosis and treatment of prostate cancers in renal-transplant recipients.

BACKGROUND: There is no consensus regarding prostate cancer in renal-transplant recipients (RTR). A questionnaire evaluating prostate cancer screening after transplantation and assessing the number, diagnostic modalities, treatment, and outcome of prostate cancer cases was mailed to 22 French renal-transplant centers. RESULTS: Among 1,680 RTR in 1998, 11 (0.65%) cases of prostate cancer were diagnosed, and among the 2,338 recipients followed up, 28 (1%) cases of prostate cancer have been diagnosed and treated. Median ages at diagnosis and at transplantation were 63 and 58, respectively. Clinical stages were T1 50% and T2 25%. Eighteen patients had a Gleason score under 7. At 18 months of mean follow-up, 2 men had died from prostate cancer, and in the curative treatment group, 16 of 17 men were alive with no evidence of disease. CONCLUSIONS: The incidence of prostate cancer in RTR appeared to be higher than expected. Prostate specific antigen (PSA) testing should be performed routinely each year in renal transplantation centers.

Adult↗
PubMed2003

Urodynamic testing predicts long-term urological complications following simultaneous pancreas-kidney transplantation.

INTRODUCTION: Combined pancreas-kidney transplantation is the treatment of choice for patients with type I diabetes mellitus associated with chronic renal failure. The introduction of the bladder drainage technique constituted a marked improvement of the surgical technique with a reduction of life-threatening complications. However, drainage of pancreatic secretions via the urinary bladder causes urological complications leading, in some cases, to cystoenteric conversion. We retrospectively analysed whether pre-operative urodynamic findings may predict the subsequent development of urological complications and influence the choice of exocrine secretion drainage. PATIENTS AND METHODS: From 1987 to 1997, 39 bladder-drained simultaneous pancreas-kidney transplantations were performed in 16 men and 23 women with a mean age of 38.5 yr. All patients underwent a complete urological assessment prior to surgery, including medical history, physical examination, urethrocystography and urodynamic assessment. RESULTS: Twenty-eight patients are alive with a mean follow-up of 62 +/- 8 months. In 60% of cases, both kidney and pancreas remain functional. Seven patients experienced recurrent lower urinary tract infections. Six patients suffered from chemical urethritis (four men and two women) and six suffered from recurrent haematuria (blood transfusions were required in two patients). One patient had incrusted stones at the site of duodenal staples. Urological complications were mostly observed in the 22 patients (79%) with abnormal urodynamic characteristics (Relative risk: 5.1). Intravenous Somatostatin failed to definitively cure these complications in most cases. Seven patients (17%) (five with urethritis, two with haematuria) required cystoenteric conversion. Two patients developed post-operative ileal fistula, one cutaneous and one into the bladder. All urinary symptoms resolved in these seven patients. CONCLUSION: The frequency of specific urinary complications is high (28%) in bladder-drained simultaneous pancreas-kidney transplantation patients. These complications are statistically more frequent in the case of an abnormal pre-transplant urodynamic assessment.

Adult↗
PubMed2003

Incidence of renal and liver rejection and patient survival rate following combined liver and kidney transplantation.

Multiple organ transplantations are used to treat chronic multiple organ failure. However, long-term mortality and graft tolerance remain to be evaluated. We carried out a retrospective and comparative analysis of 45 patients who underwent a combined liver and kidney (LK) transplantation (LKT) from the same donor. They were compared to 86 matched patients who underwent kidney (K) transplantation (KT). All patients had an organic renal failure associated with cirrhosis (n = 35) or with inherited disease (n = 10). Nineteen (42.9%) had been transplanted previously. The patients' survival rate was 85% at 1 year and 82% at 3 years. Seven patients died within the first 3 months, due to severe polymicrobial infection. Two patients in the LK population (4.2%) developed acute rejection of the kidney graft compared to 24 of the 86 matched renal transplanted patients (32.6%). In parallel, acute liver rejection was observed in 14 cases (31.1%) in the LK population. The occurrence of acute rejection was not associated with panel-reactive lymphocytotoxic antibodies (n = 16), nor with positive cross-matches (n = 3). Four of the 45 patients (8.8%) subsequently developed chronic renal allograft rejection, and 16 cases of chronic hepatic dysfunction were noted (42.2%). In conclusion, the overall survival rate following combined liver kidney transplantation is acceptable, and LKT can be proposed to patients with kidney failure associated with liver dysfunction, primary oxaluria or amyloid neuropathy. The main cause of mortality in this population was severe infectious complications. The frequency of acute kidney rejection was lower than in single transplantation.

Adolescent↗
PubMed2003

[Renal and hepatic metastasis from meningeal hemangiopericytoma].

The authors report the case of a 57-year-old woman operated in 1992 for meningeal haemangiopericytoma. Nine years later, this patient was operated for a liver tumour and then a renal tumour, which were both diagnosed as haemangiopericytoma and therefore corresponded to metastases of the primary tumour. The presence of a renal tumour in a patient previously operated for meningeal haemangiopericytoma should raise the suspicion of renal metastasis. Localized metastases can be treated by surgical resection. The possibility of late recurrence justifies annual thoraco-abdominal CT scan and bone scan for more than ten years.

Female↗