[Training simulation during the announcement of fetal malformation discovered on screening ultrasound: Results of a pilot study]. / Formation par simulation à l'annonce d'une malformation fœtale découverte en échographie de dépistage : résultats d'une étude pilote.

OBJECTIVES: Breaking bad news (BBN) to a pregnant woman with fetal abnormalities (FA) on ultrasound (US) examination is a challenge. Announcement technique influences patient reaction. Physicians receive little training in BBN. The simulation and using a BBN protocol as the English SPIKES protocol which guides the announcement consultation according to 6 steps (Setting Up, Perception, Invitation, Knowledge, Emotions and Empathy, Strategy and Summary) can be used for this teaching. The objective was to assess feasibility simulation scenarii of BBN for FA discovered during US and to evaluate the usefulness of SPIKES protocol in this situation. METHODS: Two scenarios have been created combining US simulator (US Mentor, Symbionix®) with simulated patient (SP). Scenarii objectives were to diagnose FA and break it to SP. Checklist derived from SPIKES was fulfilled by two investigators thanks to video recording, the SP and every participant (residents, physicians, fetal medicine specialists [FMS]). Participants filled out survey about the usefulness of this exercise too. RESULTS: Nine physicians (3 residents, 4 physicians, 2 FMS) produced 18 scenarii. Seventy-eight percent of physicians thought simulation was like real situation of BBN during US examination. Majority of participant (88%) found that this simulation training could help them to increase their ability to BBN and that it can be used to teach residents (89%) or physicians (100%). FMS had better SPIKES checklist than physicians (P<0,05). CONCLUSION: Simulation scenario of BBN for FA discovered during US is feasible by combining US simulator and SP. SPIKES protocol can be useful but a validated checklist should be created.

Consecutive episodes of heart and kidney failure in an "otherwise" healthy young man.

BACKGROUND: Acute renal failure is a rare occurrence in a patient with an unremarkable past medical history and should always lead to an in depth clinical study. The occurrence in the same healthy young subject, of consecutive episodes of heart failure and of acute renal failure is an even rarer event and should prompt diagnostic tests and restrict the diagnostic hypotheses. CASE PRESENTATION: We present the case of a 28 year-old man who, while waiting to undergo assessment for a mild chronic kidney disease, was diagnosed with decompensated dilated cardiomyopathy and placed on diuretics and ß-blockers. After few weeks he developed a non oligoanuric acute renal failure with a slight elevation of serum calcium. Renal biopsy proved suggestive for renal sarcoidosis; thus the hypothesis of systemic sarcoidosis with cardiac and renal involvement was possible avoiding further delay in initiation of therapy. CONCLUSIONS: Cardiac sarcoidosis is usually silent but the majority of cases are diagnosed when cardiac symptoms are present in a patient with systemic sarcoidosis. Renal involvement with granulomatous interstitial nephritis is also quite rare and can be an unexpected finding at kidney biopsy. This case highlights the need to evaluate thoroughly clinical problems that do not fit in a specific scenario and emphasizes the importance of performing a kidney biopsy in case of kidney failure of unknown etiology.

[Contribution of chromosomal microarray analysis by a multidisciplinary prenatal diagnosis center]. / Apport de l'analyse chromosomique par puce à ADN dans un centre de diagnostic prénatal pluridisciplinaire.

OBJECTIVE: Chromosomal analysis by array CGH is a cytogenetic technique that has opened its application to prenatal diagnosis in recent years. The main objective of the study was to analyze the contribution for couples using chromosomal analysis by array CGH in a CPDPN. METHODS: A retrospective cohort study was conducted in 2015 in a CPDPN. All the patients with array CGH analysis were included in the study. The analysis indications were CN≥3.5mm, ultrasound signs, intra-uterine growth retardation and fetal deaths. Data were collected in the prenatal diagnosis and genetic records. RESULTS: In total, 155 patients underwent analysis by array CGH, which corresponds to 36% of patients with invasive sampling indication. Fifteen CGH analysis were positive which represents 9.6% of indications. None of those diagnoses was possible with standard karyotype. These positive results have changed the outcome of pregnancy and what to do for a future pregnancy in 54% of cases. CONCLUSION: Array CGH enables a diagnostic gain despite a delicate interpretation and changes taking care of patients in future pregnancies. These results should be confirmed in a prospective multicenter study.

Pretransplant and protocol biopsies may help in defining short and mid-term kidney transplant outcome.

Although many variables may affect long-term graft survival no biomarker is available to identify donor kidney with poor quality and with inadequate short and long-term outcome. While in marginal donors pre-transplant renal biopsies are commonly performed to establish if donor kidneys are suitable for transplantation they are not performed in standard donors. In this study we assessed the relevance of pre-transplant morphological features on post-transplant renal function and evaluated the association between perioperative parameters with posttransplant histological and clinical findings. Kidney transplant recipients undergone pre-transplant and post transplant protocol biopsies at 1, 6, and 12 months were enrolled in the study. Perioperative and posttransplant clinical and biochemical parameters were recorded. Semiquantitative analysis of PAS stained kidney sections was used to determine the degree of lesions. Glomerular volume was measured by computed morphometry. A strong inverse correlation was found between donor age and renal graft function at 1, 6, and 12 months after transplantation. A prompt functional recovery was associated with a better renal function at 6 months and one year. Kidneys with higher glomerular volume demonstrated a lower serum creatinine at 1 month. Higher tubulo-interstitial grading at protocol biopsies was associated with a poor renal function at 1 month. Our findings confirm the importance of donor age in kidney transplant long-term outcome and demonstrate that pretransplant and protocol biopsies are valid options to determine graft outcome and to define therapeutic strategies and tailor immunosuppressive regimen for each patient.

Effects of continuous erythropoietin receptor activator (CERA) in kidney transplant recipients.

Erythropoietin-stimulating agents (ESAs) are commonly used to treat anemia in kidney transplant recipients (KTRs). Since 2007, continuous erythropoietin receptor activator (CERA) has been one of the newest recombinant ESAs to treat anemia in dialysis and nondialysis patients with chronic kidney disease. The efficacy of CERA to manage anemia has not been extensively evaluated in KTRs. We evaluated safety, efficacy, and satisfaction among KTRs treated with CERA. We enrolled 19 anemic KTRs (60 ± 9.3 y) who were treated with short-acting ESA for ≥24 weeks. They were shifted to the equivalent dose of CERA and followed for 24 weeks. We measured serum hemoglobin, hematocrit, creatinine, iron, ferritin, and transferrin. To investigate tolerance to and satisfaction with short-acting ESA and CERA, questionnaires were administered to the patients before shifting to CERA and at the end of the follow-up. After 6 months, CERA induced an increase in hemoglobin levels (12.3 ± 0.8 vs 11.2 ± 1.1 g/dL; P = .002, CERA vs short-acting ESA, respectively). In 2 patients treatment was discontinued because the hemoglobin increased to >13 g/dL. No significant differences were observed in serum iron and creatinine between short-acting ESA and CERA throughout the study. The questionnaires showed better compliance to CERA treatment with reduced pain at the injection site, which led subjects to prefer CERA to short-acting ESA. In summary, CERA showed better control of anemia compared with short-acting ESA. It was preferred by the majority of patients, mainly because of the reduced number of monthly injections. Our results demonstrated CERA to be effective, safe, and well tolerated in the management of anemia in KTRs.

Sirolimus prevents short-term renal changes induced by ischemia-reperfusion injury in rats.

BACKGROUND: Ischemia-reperfusion (I/R) is present at various degrees in kidney transplants. I/R plays a major role in early function and long-term survival of renal allograft. The purpose of our study was to determine if immunosuppressants modulate I/R in a model that separates I/R from all immune responses. METHODS: Sprague-Dawley rats with monolateral renal I/R received daily cyclosporine (A), tacrolimus (B), sirolimus (C) or saline (D). Sham-operated rats received saline (E). After 30 days, glomerular filtration rate for each kidney was measured by inulin clearance. Kidney injury was examined, and TGF-ß, fibronectin and metalloproteases were evaluated by real-time PCR, Western blot and zymography. RESULTS: Sirolimus, but not cyclosporine and tacrolimus, prevented a glomerular filtration rate decrease in I/R kidneys (403 ± 303 vs. 1,006 ± 484 µl/min, p < 0.05; 126 ± 170 vs. 567 ± 374 µl/min, p < 0.05; 633 ± 293 vs. 786 ± 255; A, B and C group, respectively, I/R vs. contralateral kidneys). Sirolimus reduced ED-1+ cell infiltrate, interstitial fibrosis and intimal thickening of small vessels observed in I/R kidneys of controls and calcineurin inhibitor-treated rats. Tacrolimus and cyclosporine increased fibronectin and TGF-ß expression and matrix deposition. Only sirolimus increased metalloprotease activity. CONCLUSIONS: Sirolimus but not calcineurin inhibitors prevented I/R-induced kidney injury.

Effects of sirolimus on human mesangial cells.

Mesangial cell (MC) proliferation and production of extracellular matrix or loss of MC are both central findings in a number of renal proteinuric diseases. However, the role of MC as components of the glomerular filtration barrier and whether MC alterations induce changes in the glomerular filtration barrier leading to proteinuria are still matters of debate. The effects of Sirolimus (SRL) in proteinuric nephropathies is controversial: some papers have indicated a reduction and others, an increase in proteinuria after sirolimus treatment. Considering the pivotal role of MC in the pathogenesis of many chronic nephropathies, we evaluated the effect of SRL on cultured human MC. We treated primary human MC cultures with SRL, or platelet-derived growth factor (PDGF) or SRL + PDGF, or dimethylsulfoxide, the SRL vehicle, as a control. PDGF was used to activate MC. After 48 hours treatment, MC showed a significant growth increase that was significantly reduced by SRL (P < .01). Apoptosis, determined by the TUNEL assay and flow cytometry, was not modified by the treatments at 24 hours. SRL treatment increased significantly the number of alpha-smooth muscle actin-positive cells compared with controls (P < .05). Cells treated with SRL and SRL + PDGF showed significant changes in morphology with increased mean cell surface, perimeter, and maximum diameter (P < .01) but not protein content. Furthermore, MC treated with SRL showed decreased migration through polycarbonate membranes. The changes induced by SRL may help to explain some of the in vivo effects observed in SRL-treated patients.

Increased asymmetric dimethylarginine serum levels are associated with acute rejection in kidney transplant recipients.

Asymmetric dimethylarginine (ADMA) has been identified as a marker of endothelial dysfunction and an independent risk factor for cardiovascular events in uremic subjects. This study evaluated ADMA plasma levels in kidney transplant recipients. ADMA levels were serially measured during the first year posttransplantation in 41 recipients treated with cyclosporine regimen (CY), sirolimus (SIR), or low-dose cyclosporine plus everolimus (E). Homocysteine, C reactive protein (CRP), nitric oxide (NO), and standard routine laboratory analyses were determined serially. ADMA significantly increased at 6 months posttransplantation, but was significantly lower among patients on SIR or E. NO was only slightly reduced in patients with increased ADMA levels. Interestingly, ADMA was significantly increased during the first 4 days posttransplantation in patients who experienced acute rejection during the first 6 months after transplantation. The same group of patients demonstrated higher levels of CRP and systolic blood pressure before transplantation. Our results demonstrated that ADMA was increased in patients on CY at 6 months. When increased soon after transplantation ADMA may be associated with episodes of acute rejection in kidney transplant recipients. The presence of elevated systolic blood pressure, as well as CRP and ADMA levels, suggested a role for endothelial dysfunction in the development of acute rejection episodes among deceased donor kidney transplant recipients.

The improvement of ischemia/reperfusion injury by erythropoetin is not mediated through bone marrow cell recruitment in rats.

BACKGROUND: Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure in kidney transplantation; however, the mechanisms of kidney damage and repair are not yet clear. So far no treatment has been effective to prevent I/R injury. In the present study we evaluated the effect of erythropoetin (EPO) in I/R injury in rats. We investigated the role of bone marrow cells (BMC) in kidney repair and the effect of EPO on BMC recruitment. MATERIALS AND METHODS: Female Sprague Dawley rats transplanted with male BMCs underwent I/R injury. In the treatment group rats received 5000 IU of EPO 30 minutes before renal ischemia. At 2 and 4 weeks after I/R, rats were humanely killed and we measured creatinine clearance (glomerular filtration rate [GFR]), proteinuria, and body weight (BW). Renal tissue was harvested for histologic and molecular analysis. Fluorescein in situ hybridization (FISH) and TUNEL were used to determined the presence of male cell chimerism and apoptosis in renal tissue. RESULTS: At 4 weeks after I/R, EPO significantly improved GFR (1.8 +/- 0.2 vs 1.2 +/- 0.14 mL/min; P < .05). No significant differences between EPO and control rats were observed in proteinuria, BW, and hemoglobin levels at 2 and 4 weeks. After death, the kidney showed only minimal tubulointerstitial changes, which were more marked in control rats. FISH analysis demonstrated a low degree of microchimerism, not significantly different between EPO and control rats. Apoptosis decreased between 2 and 4 weeks after I/R, in both EPO and control groups. CONCLUSION: EPO improved GFR and injury at 4 weeks after I/R; however, it did not enhance the recruitment of BMC.

Rapamycin reduces proteinuria and renal damage in the rat remnant kidney model.

Rapamycin is an immunosuppressive drug used to prevent acute allograft rejection in solid organ transplantation. It shows less nephrotoxicity than calcineurin inhibitors. We evaluated the effect of rapamycin in rats undergoing 5/6 nephrectomy, a model of proteinuric and progressive renal failure. Fourteen days after surgery rats were randomized either to receive rapamycin or to remain untreated (control). Rats were humanely killed on day 91; serum creatinine, creatinine clearance, and proteinuria were assessed. Renal sections were stained with periodic acid-Schiff to evaluate glomerular volume (Gv), glomerulosclerosis (GS) and tubulointerstitial damage (TIS); we evaluated GS and TIS by Sirius red staining (SR). Epithelial-to-mesenchymal transition (EMT) was assessed by immunohistochemistry. Rapamycin affected neither serum creatinine nor creatinine clearance; it reduced Gv (controls, 5.9 +/- 3.1 x 10(6); rapamycin, 1.3 +/- 0.7 x 10(6) microm(3)) and proteinuria (control, 349 +/- 146; rapamycin, 56 +/- 27 mg/24 h; P < .05); rapamycin ameliorated GS (control, 78 +/- 7; rapamycin, 36 +/- 7%; P < .05; SR: control, 13.2 +/- 3.5; rapamycin, 3.8 +/- 1.0%; P < .05), and TIS (control, 3.25 +/- 0.5; rapamycin, 1.0 +/- 0.1; P < .05; SR: control, 29 +/- 3; rapamycin, 11 +/- 3%; P < .05). Rapamycin reduced alphaSMA (control, 3.25 +/- 0.5; rapamycin, 1.0 +/- 0.1; P < .05), VIM (control, 3.5 +/- 0.6; rapamycin, 1.0 +/- 1.4; P < .05), and CD68(+) cells infiltration (control, 110 +/- 43; rapamycin, 24 +/- 1 cells; P < .05). Rapamycin slows the progression of renal damage in the rat remnant kidney and may represent a novel approach to the treatment of chronic kidney disease.

Effectiveness of mycotoxin sequestration activity of micronized wheat fibres on distribution of ochratoxin A in plasma, liver and kidney of piglets fed a naturally contaminated diet.

A study was carried out to determine the ability of dietary micronized wheat fibres (MWF) to decrease the levels of ochratoxin A (OTA) in plasma, kidney and liver of piglets fed a naturally contaminated diet. A total of 96 piglets (weighting 11.4+/-1.5 kg) were fed one of four different diets for 28 days. Diets included (1) control diet, (2) control diet with MWF (1%), (3) OTA naturally contaminated diet (117.45+/-4.74 ng/g), (4) OTA naturally contaminated diet (118.13+/-2.85 ng/g) with MWF (1%). No difference in feed efficiency (P>0.05) could be observed between the different diets. The absolute weight of kidneys and liver were significantly higher in pigs fed the OTA-contaminated diet (diet 3) as compared to the control diet (diet 1) or to the control diet amended with MWF (diet 2) (P<0.05). However the use of MWF (diet 4) significantly protected against these weight changes. A significant protective effect of MWF was also observed in terms of OTA concentration in plasma (45.6% decrease), kidney (40.8% decrease) and liver (26.5% decrease). These results suggest that the addition of MWF is effective in decreasing the bioavailability of OTA from contaminated diets in piglets.

Chronic toxicity of fumonisins in turkeys.

Fumonisins are mycotoxins that are found worldwide. They are mainly produced by Fusarium verticillioides during its development on corn. The main toxic effects of these molecules have been well characterized in poultry in the case of acute exposure, but the subclinical and economic effects of chronic exposure are less known. Whereas the latest European recommendations suggest that maximal levels of fumonisins in corn could reach 60 mg/kg and the maximal contamination of poultry feeds could reach 20 mg/kg, no study is available at this level in turkeys. The aim of the present work was thus to characterize the effects of exposure to fumonisins (concentrations of 0, 5, 10, and 20 mg of fumonisin B1 + fumonisin B2/kg of feed) on feed consumption and growth in turkeys over a period of 9 wk. Main biochemical parameters of the liver and alteration of sphingolipid metabolism were investigated in plasma, liver, and kidney. The main results showed no effect on feed consumption and growth in exposed turkeys. Moreover, no effect was observed on the weight of tissues and markers of liver injury. By contrast, a disruption of sphingolipid metabolism was clear at a level of exposure of 10 and 20 mg of fumonisin B1 + fumonisin B2 mg/kg of feed. Both hepatic and kidney concentrations of sphinganine increased gradually throughout the exposure period. These results reveal that disruption of sphingolipid metabolism is an early and sensitive biomarker of fumonisins exposure in turkeys; the consequences on these alterations remain to be established.

Ingestion of low doses of deoxynivalenol does not affect hematological, biochemical, or immune responses of piglets.

Deoxynivalenol (DON), a mycotoxin produced by Fusarium spp., is a frequent contaminant of cereals. Because of their rich cereal diet, pigs could be exposed to this mycotoxin. Pigs are among the animal species showing the greatest sensitivity to DON. Effects of intermediate to high levels of DON on pigs are well known and include feed refusal, decreased feed intake, and alteration of the immune response. Effects of low levels of DON, which are commonly detected in contaminated feed, remain unknown. The aim of this study was to investigate the effect of a diet naturally contaminated with a low concentration of DON (0, 280, 560, or 840 microg/kg of feed) on performance of weanling piglets and on 34 hematological, biochemical, and immune variables. Low doses of DON did not alter the animal performances (feed intake and BW gain). Such low levels of DON did not modify the 9 hematological variables measured (including white blood cell, red blood cell, and platelet counts, relative numbers of neutrophils and lymphocytes, and hematocrit and hemoglobin concentrations) or the 18 biochemical variables tested (including cations, glucose, urea, creatinine, bilirubin, cholesterol and triglyceride concentrations, and plasma enzyme activity). Similarly, no effect of low doses of DON was observed on the immune responses of the animals (immunoglobulin subset concentration, lymphocyte proliferation, and cytokine production).

The gender marking effect in spoken word recognition: the case of bilinguals.

It has been known for some time that the recognition of a noun is affected by the gender marking, such as masculine or feminine, that is carried by a preceding word. In this study, we used auditory naming to examine how early and late English-French bilinguals react to gender marking when processing French. The early bilinguals showed clear facilitation and inhibition effects, but the late bilinguals were totally insensitive to gender marking, whether congruent or incongruent. The results are discussed in terms of current accounts of gender processing as well as age of acquisition and regular use of the gender-marking language.

Melanoma prevention: evaluation of a health education campaign for primary schools.

OBJECTIVE: To evaluate the effectiveness of an educational campaign aimed toward limiting children's sun exposure. DESIGN: Prospective, multicenter trial with before-after comparison. A school-based campaign was presented as a game during a 4-week period (May 25 to June 1992) with primary school teachers as game hosts. Children were interviewed with a standardized questionnaire in September before (1991) and after (1992) the campaign. Comparisons between the children's answers before and after the campaign were made using paired chi2 tests and analysis of variance. SETTING: Five French primary schools. SUBJECTS: All children in their fourth year of primary school (228 children aged 9 years). MAIN OUTCOME MEASURES: Changes after the campaign in children's answers concerning their knowledge, attitude, and behavior toward the sun during summer holidays. RESULTS: Compared with the precampaign answers, more children after the campaign claimed to protect themselves from the sun with a hat (33.7% vs 23.8%; P = .01) or sunscreen (34.8% vs 25.4%; P = .03), avoided going outside during the sunniest hours (76.8% vs 66.0%; P = .02), reapplied sunscreens (22.1% vs 10.6%; P<.001), considered that a T-shirt and shade provided better protection than sunscreen (82.7% vs 74.8%; P = .05), considered sunlight as a risk factor for skin cancer (74.9% vs 50.7%; P<.001), and spent significantly less time in the sun with their arms (P = .005), trunk, legs, and head uncovered (P<.001). Children with a fair complexion, who were the target of this campaign, showed the best improvement in their responses. CONCLUSION: Health education campaigns can be effective in terms of improving the knowledge, attitude, and behavior of young children.

Dialect effects in vowel perception: the role of temporal information in French.

The importance of vowel duration for specifying vowel contrasts differs across languages. In English, for example, a number of vowel pairs are acoustically differentiated by both temporal and spectral information, whereas in standard French temporal information plays a much more minor role. Gottfried and Beddor (1988) reported that the effectiveness of vowel duration in perception varies accordingly: For native speakers of English, but not native speakers of standard French, a change in vowel duration affected the perceptual identity of a vowel contrast. We tested the hypothesis that the relative prominence of vowel duration within different dialects of a given language also has perceptual consequences. Vowel duration plays a much more important role in the phonological system of Swiss French than standard French. Given this, we predicted that native speakers of Swiss French, unlike native speakers of standard French, would use temporal information when identifying vowels. Our prediction was confirmed. These findings indicate that just as there are cross-language differences in fundamental aspects of speech perception, so too are there cross-dialect differences, and they support the view that the perceptual mapping between acoustic signal and vowel category is sensitive to global aspects of the listener's phonological system.

The gender-marking effect in spoken word recognition.

In this paper we examine whether the recognition of a spoken noun is affected by the gender marking--masculine or feminine--that is carried by a preceding word. In the first of two experiments, the gating paradigm was used to study the access of French nouns that were preceded by an appropriate gender marking, carried by an article, or preceded by no gender marking. In the second experiment, subjects were asked to make a lexical decision on the same material. A very strong facilitatory effect was found in both cases. The origin of the gender-marking effect is discussed, as well as the level of processing involved--lexical or syntactic.

Base-language effects on word identification in bilingual speech: evidence from categorical perception experiments.

The categorical perception paradigm was used to investigate whether French-English bilinguals categorize a code-switched word as French or English on the basis of its acoustic-phonetic information alone or whether they are influenced by the base-language context in which the word occurs, that is, by the language in which the majority of words are spoken. Subjects identified stimuli from computer-edited series that ranged from an English to a French word as either the English or the French endpoint. The stimuli were preceded by either an English or a French context sentence. In accord with previous studies (Grosjean, 1988), it was found that the base language had a contrastive effect on the perception of a code-switched word when the endpoints of the between-language series were phonetically marked as English and French, respectively. When the endpoints of the series were phonetically unmarked and thus compatible with either language, however, no effect of the base language was found; in particular, we failed to find the assimilative effect that has been observed with other paradigms (Grosjean, 1988; Soares and Grosjean, 1984; Macnamara and Kushnir, 1971). The current results provide confirming evidence that the perception of a code-switched word is influenced by the base-language context in which it occurs and, moreover, that the nature of the effect depends on the acoustic-phonetic characteristics of the code-switched word. In addition, the finding that a contrastive effect occurs across all paradigms used to date, but that an assimilative effect occurs in only some paradigms, suggests that these two context effects may arise at different stages of processing.