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Biomedical subjects

P Rieu

Publications and source records attributed to P Rieu.

At least 19 recordsLinked to original sources

[Pregnancy after renal transplantation. Obstetrical follow-up and impact on renal graft function].

OBJECTIVE: The aim of this study is to give the results of our experience about pregnancies among the renal transplantation patients and to assess the impact of the pregnancy on renal graft function. PATIENTS AND METHODS: Twenty pregnancies from 17 renal transplant recipients were analysed and long-term outcome of the renal graft was studied. We analysed the outcomes from clinical and biological data before, during and after pregnancy. RESULTS: Mean patient age was 30.3+/-3.5 years and meantime between transplantation and the onset of pregnancy was 62.4+/-34.5 months. There was no significant difference between the biological data before and after pregnancy. We did not observe any acute rejection. The mean maternal complications were preeclampsia in 35%, low birth weight in 39%, prematurity in 45% and cesarean sections in 55%. There is no impact of the pregnancy on the renal graft during the follow-up (3 years). The follow-up revealed 2 cases of chronic rejection. DISCUSSION AND CONCLUSION: A multi-disciplinary approach of pregnancy in renal recipients and an interval of 2 years after kidney transplantation are necessary. There are more complications during pregnancy without increased risks of graft lose.

Adult↗

[Infective lithiasis].

"Infection Lithiasis" refers to calculi that occur with persistent urinary tract infection. Stones composed of magnesium ammonium phosphate (struvite) and carbonate apatite, called "triple phosphate" stones, are the more common type of infection lithiasis. These stones are also called "staghorn" calculi because they may grow rapidly and fill the entire collecting system. They form during urinary infection with urea-splitting micro-organism. They may originate de novo or complicate a lithiasis when pre-existing stones are colonized with urea-splitting bacteria. They represent about 2-3% of stones referred for laboratory analysis. This article reviews the epidemiology, pathogenesis, clinical features, and management of struvite stones. A singular pathologic entity recently described, called "encrusted cystitis or encrusted pyelitis", mainly caused by Corynebacterium urealyticum is also review. Infection lithiases caused by non-urease-producing bacteria may also occur and are examined in this article. Finally, the controversial role of nanobacteria in nephrolithiasis is discussed.

Humans↗

The adenylate cyclase toxin of Bordetella pertussis binds to target cells via the alpha(M)beta(2) integrin (CD11b/CD18).

The adenylate cyclase toxin (CyaA) of Bordetella pertussis is a major virulence factor required for the early phases of lung colonization. It can invade eukaryotic cells where, upon activation by endogenous calmodulin, it catalyzes the formation of unregulated cAMP levels. CyaA intoxication leads to evident toxic effects on macrophages and neutrophils. Here, we demonstrate that CyaA uses the alpha(M)beta(2) integrin (CD11b/CD18) as a cell receptor. Indeed, the saturable binding of CyaA to the surface of various hematopoietic cell lines correlated with the presence of the alpha(M)beta(2) integrin on these cells. Moreover, binding of CyaA to various murine cell lines and human neutrophils was specifically blocked by anti-CD11b monoclonal antibodies. The increase of intracellular cAMP level and cell death triggered by CyaA intoxication was also specifically blocked by anti-CD11b monoclonal antibodies. In addition, CyaA bound efficiently and triggered intracellular cAMP increase and cell death in Chinese hamster ovary cells transfected with alpha(M)beta(2) (CD11b/CD18) but not in cells transfected with the vector alone or with the alpha(X)beta(2) (CD11c/CD18) integrin. Thus, the cellular distribution of CD11b, mostly on neutrophils, macrophages, and dendritic and natural killer cells, supports a role for CyaA in disrupting the early, innate antibacterial immune response.

Adenylate Cyclase Toxin↗

[Medical treatment of cystinuria: evaluation of long-term results in 30 patients].

OBJECTIVE: Because urinary hyper-excretion of cystine is permanent in homozygous cystinuric patients, stone recurrence is frequent and may alter renal function. Identification of factors predictive of success of medical treatment (no further urological procedure required) is therefore needed to improve patient management. PATIENTS AND METHODS: Thirty adult patients with homozygous cystinuria and urolithiasis were referred to the nephrology department of the Necker Hospital from 1963 to 1999, with a mean follow-up of medical therapy of 10.5 +/- 8.4 years. The basal treatment schedule was hyperdiuresis and alkalinization with thiol derivative (D-penicillamine or tiopronine) added when needed. RESULTS: Overall incidence of urological procedures decreased from 0.33/pt-year in the pretherapeutic period to 0.15 on treatment (p < 0.01), a 55% reduction. Sixteen patients (53%) did not require any urological procedure during follow-up. The only significant difference between those patients and the other 14 in whom medical therapy failed was the daily urine volume (3.2 l/day in the former compared with 2.4 l/day in the latter, p < 0.001). CONCLUSION: Regular medical therapy was able to stop stone disease activity in the long term in more than half of the patients. Sustained hyperdiuresis, with a daily urine volume > 3 liters, appears as a major factor of therapeutic success, even in patients treated with thiols.

Adolescent↗

Incidence of surgical site infections in pediatric patients: a 3-month prospective study in an academic pediatric surgical unit.

During a 3-month period 259 pediatric surgical procedures in 236 patients were followed for the development of surgical site infections (SSI): 17 sites became infected, an overall infection rate of 6.6%. The incidence in our study was therefore higher than expected. As expected, the infection rate increased according to wound contamination: dirty sites had a SSI rate of 30%. Emergency procedures, operation duration over 1 h, and inpatients showed a statistically significant higher risk of developing SSI. Although there were differences between males and females, individual surgeons, and the use of antibiotic prophylaxis, these differences were not statistically significant.

Ambulatory Surgical Procedures↗

Medical treatment of cystinuria: critical reappraisal of long-term results.

PURPOSE: We evaluated long-term results of a contemporary medical therapeutic regimen in patients with cystinuria and analyzed factors predictive of therapeutic success. MATERIALS AND METHODS: A total of 27 adults with cystine urolithiasis were treated at our institution for 1.3 to 32 years (mean 11.6, overall 312 patient-years). We obtained data on the pre-referral period for 274 patient-years overall. Basic therapy included hyperdiuresis and alkalization. The thiols D-penicillamine or tiopronin were added when standard therapy failed to prevent new stones and stone growth or dissolve preexisting stones. X-ray and echography were performed every 4 months during the initial 2 years and every 6 months thereafter. RESULTS: In the pre-referral period 256 stone episodes occurred and 81 urological procedures were performed in 24 patients (0.93 and 0. 29 per patient-year, respectively). Nine patients were treated with added thiols. During the therapeutic period the incidence of stone episodes decreased to 66 (0.20 per patient-year, p <0.001), while the need for urological procedures decreased to 44 (0.14 per patient-year, p <0.001). No further urological procedures were required in 15 patients, including 4 treated with thiols. However, the remaining 12 patients, including 5 treated with thiols, underwent 1 to 7 procedures each (mean 0.26 per patient-year). In the 2 groups mean daily cystine excretion plus or minus standard deviation at baseline (863 +/- 253 versus 761 +/- 270 mg. daily) and mean urinary pH of about 7.4 did not differ significantly. However, daily urine volume was significantly higher in patients with arrested stone formation (3,151 +/- 587 versus 2,446 +/- 654 ml./24 hours, p = 0.006). CONCLUSIONS: Our study provides evidence that a regularly followed medical program based on high diuresis and alkalization with second line addition of thiols may arrest or markedly decrease cystine stone formation and preclude the need for urological procedures in more than half of the patients. However, patients poorly compliant with hyperdiuresis remain at risk for recurrence. We suggest that maintaining a daily urine volume of greater than 3 l. is essential for therapeutic success regardless of whether thiol derivatives are administered.

Adolescent↗

Cutis marmorata telangiectatica congenita: report of 18 cases.

We report 18 patients with cutis marmorata telangiectatica congenita (CMTC) who visited the University Hospital Nijmegen between 1982 and 1999. In 11 patients (61%), associated abnormalities of varying severity were observed. Three of these patients had a previously described distinct syndrome comprising CMTC, a naevus flammeus at the upper lip/philtrum, macrocephaly and syndactyly, among other abnormalities. Findings in the other eight patients with associated abnormalities included hydrocephalus, hyperplasia/hypoplasia (body asymmetry), anal atresia, hearing loss, cardiovascular abnormalities, strabismus hypothyroidism, haemangioma, naevus anaemicus, café-au-lait spot, lipoma and an elevation of the right diaphragm. All cases were sporadic.

Abnormalities, Multiple↗

Redox regulation of beta2-integrin CD11b/CD18 activation.

Although the central role of beta2-integrin CD11b / CD18 in neutrophil functions is well recognized, signaling pathway that regulate integrin activation remain to be elucidated. We analyzed the contribution of oxido-reduction mechanisms in this signaling. Exogenously added H(2)O(2) induced CD11b/CD18-dependent neutrophil adhesion and expression of an integrin activation neoepitope recognized by monoclonal antibody (mAb) clone 24. H(2)O(2)-triggered beta2-integrin activation was inhibited by tyrosine kinase inhibitors and by complexing sulfhydryl groups with phenylarsine oxide (PAO). CD11b/CD18-dependent adhesion and mAb 24 antigen expression triggered by physiological agonists such as TNF-alpha were inhibited by diphenylene iodonium (DPI, an inhibitor of flavoprotein oxidoreductase), by free radical scavengers, by tyrosine kinase inhibitors and by PAO. No inhibition was observed when adhesion was induced by the integrin-activating KIM 185 mAb. Taken together, these results emphasize the importance of an oxidative S-thiolation step(s) in the tyrosine kinase-dependent signaling pathway leading to beta2-integrin activation. H(2)O(2) would directly mediate this oxidative reaction and bypass the initial agonist/receptor pathway to promote integrin-dependent adhesion. The putative oxidase(s) involved in this process is not NADPH oxidase, since adhesion of neutrophils from patients with chronic granulomatous disease was normal and inhibited by scavengers and DPI. These data shed a new light on the regulation of integrin activation required for cell migration into inflamed organs.

CD18 Antigens↗

Treatment of cystinuria.

Cystine urolithiasis is the only clinical expression of cystinuria, an autosomal recessive genetic defect of the transepithelial transport of cystine and other dibasic amino acids in the kidney. Stones form due to the increased excretion of cystine, which is poorly soluble at normal urine pH. Cystine stones are often resistant to extracorporeal shock wave lithotripsy, so that percutaneous surgery or ureteroscopy are the preferred techniques of stone extraction. Medical preventative treatment is based on high diuresis (>/=1.5 l/m(2) per day) well distributed throughout the day and night, and urine alkalinization up to pH 7.5 by means of sodium bicarbonate and/or potassium citrate. When these basal measures are ineffective at preventing stone recurrence or dissolving pre-existing stones, sulfhydryl agents such as D-penicillamine or tiopronin, which form highly soluble mixed disulfides with cystine moieties, are to be added to urine dilution and alkalinization, especially when cystine excretion is in excess of 750 mg/day (3 mmol/day). Frequent clinical and ultrasound follow-up is needed to encourage patient compliance and assess efficacy and tolerance of treatment.

Adult↗

Henoch-Schönlein nephritis in children and adults. Morphological features and clinicopathological correlations.

Rheumatoid purpura or Henoch-Schönlein syndrome is an IgA vasculitis affecting small vessels. The acute disease progresses by successive flare-ups of limited duration. Long-term prognosis depends mainly on the degree of initial renal damage. A review of the literature shows that renal involvement occurs in about 33% of children and 63% of adults with rheumatoid purpura. The most typical manifestation is segmentary focal glomerulonephritis, always associated with granulous IgA deposits in the mesangium. When renal signs are severe enough to warrant renal biopsy (generally at urine protein > 1 g/d and/or organic renal failure) the risk of developing chronic renal failure is 18% in children and 28% in adults. The best prognostic features are histological. The percentage of crescents, the presence of interstitial fibrosis and the presence of dense sub-epithelial deposits are correlated with risk of chronic renal failure. This risk is high (47%) in children with crescents in more than half the glomeruli. In adults, the percentage of crescents associated with unfavorable course appears to be lower than 50%. Predictions are only valid if no further renal flare-up occurs. In addition, histology cannot precisely predict the course of persistent renal sequelae. The severity of sequelae determines the risk and the rapidity of developing chronic renal failure. It is thus recommended to follow patients with Henoch-Schönlein nephritis for long periods.

Acute Disease↗

Two functional states of the CD11b A-domain: correlations with key features of two Mn2+-complexed crystal structures.

In the presence of bound Mn2+, the three- dimensional structure of the ligand-binding A-domain from the integrin CR3 (CD11b/CD18) is shown to exist in the "open" conformation previously described only for a crystalline Mg2+ complex. The open conformation is distinguished from the "closed" form by the solvent exposure of F302, a direct T209-Mn2+ bond, and the presence of a glutamate side chain in the MIDAS site. Approximately 10% of wild-type CD11b A-domain is present in an "active" state (binds to activation-dependent ligands, e.g., iC3b and the mAb 7E3). In the isolated domain and in the holoreceptor, the percentage of the active form can be quantitatively increased or abolished in F302W and T209A mutants, respectively. The iC3b-binding site is located on the MIDAS face and includes conformationally sensitive residues that undergo significant shifts in the open versus closed structures. We suggest that stabilization of the open structure is independent of the nature of the metal ligand and that the open conformation may represent the physiologically active form.

Amino Acid Substitution↗

Solvent-accessible residues on the metal ion-dependent adhesion site face of integrin CR3 mediate its binding to the neutrophil inhibitory factor.

Neutrophil adhesion-dependent functions such as chemotaxis, spreading, and phagocytosis are inhibited by neutrophil inhibitory factor (NIF), a glycoprotein produced by the hookworm Ancylostoma caninum. The NIF binding site has been localized to the A-domain of integrin CR3 (CD11b/CD18) and shown to be metal-dependent. The recently solved crystal structure of the A-domain from CD11b revealed a putative metal ion-dependent adhesion site (MIDAS) on the top of the structure. To determine if NIF binds to the A-domain at its MIDAS face, amino acid substitutions involving 24 residues present in surface loops and adjacent helices in the structure were created. The expressed CD11b A-domain and CR3 heterodimers were then tested in a blinded manner for their ability to bind to biotinylated NIF. The solvent-exposed Gly143, Asp149, Glu178-Glu179, and Arg208, all located on the MIDAS face, in close proximity to the metal ion, were involved in CR3-NIF interaction. These data show that the natural integrin antagonist, NIF, binds to CR3 through the MIDAS region and identify putative contact residues in this region that could be targeted therapeutically.

Amino Acid Sequence↗

A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosis: a homeostatic mechanism in inflammation.

In mice selectively deficient in CD11b/CD18, a beta 2 integrin, chemoattractant-induced leukocyte adhesion to microvascular endothelium in vivo was reduced. Paradoxically, thioglycollate-induced neutrophil accumulation in the peritoneal cavity was increased and was associated with a significant delay in apoptosis of extravasated cells. The extravasated cells had a near absence of neutrophil phagocytosis and a reduction in oxygen free radical generation, which may contribute to the observed defect in apoptosis. This is supported by our in vitro studies, in which phagocytosis of opsonized particles by human neutrophils rapidly induced apoptosis that could be blocked with CD11b/ CD18 antibodies. Reactive oxygen species are the intracellular link in this process: phagocytosis-induced apoptosis was blocked both in neutrophils treated with the flavoprotein inhibitor diphenylene iodonium and in neutrophils from patients with chronic granulomatous disease, which lack NADPH oxidase. Thus, CD11b/CD18 plays a novel and unsuspected homeostatic role in inflammation by accelerating the programmed elimination of extravasated neutrophils.

Animals↗