Peritoneal Sclerosis in a Patient on Long-term Continuous Ambulatory Peritoneal Dialysis (CAPD). : An Autopsy Case.

若年性ネフロン癆による慢性腎不全でCAPD (continuous ambulatory peritoneal dialysis)導入し, 6年6ヵ月後に死亡した20歳男性の1剖検例を報告した。CAPD導入数カ月後, 腹膜炎による除水能低下を起こしたが, 約5ヵ月後に回復した。CAPD導入1年5ヵ月以降重症な腹膜炎罹患により除水能低下状態が遷延したが, 次第に回復した。しかし, 体液貯留傾向のため, 3年2ヵ月後より高張透析液を使用し除水量の増加を得たが, 3年9ヵ月後に不可逆的な除水能低下状態となった。一方, クレアチニンの透析排液/血漿濃度比(D/P)から見た溶質除去能は, その約半年後まで保たれており, 血清クレアチニン値の上昇は軽度であった。剖検にて腹膜の線維性肥厚と高度の内腔狭窄を伴う動静脈硬化を認め, 腹膜硬化症と診断した。本例の腹膜硬化症は, 頻回の腹膜炎と高張透析液の使用が主な原因と考えられた。腹膜機能を長期に維持するためには, 腹膜炎の予防と高張透析液の使用を最小限にすることが重要と考えられた。A 20-year-old man, treated with continuous ambulatory peritoneal dialysis (CAPD) for 6.5 years because of-end-stage renal disease due to juvenile nephronophthysis, died of ultrafiltration failure, and the morphological examination of peritoneum was carried out at autopsy. Nine episodes of peritonitis developed, and ultrafiltration transiently decreased after each episodes. At 2 years after the start of CAPD, severe peritonitis occurred, and then his body weight and blood pressure gradually increased. At 4 years after the beginning of CAPD, when hyperosmotic dialysate was frequently used, ultrafiltration was irreversively deteriorated. On the other hand, creatinine dialysate/plasma ratio remained within normal limits for about several months, and the increase in the level of serum creatinine was very little. The peritoneum obtained at autopsy revealed marked fibrous thickening as well as the conspicuous luminal narrowing of arteries and veins due to intimal thickening. The development of peritoneal sclerosis seemed to be related with the frequency and severity of peritonitis and the use of hyperosmotic dialysate

L'Auto-vélo : automobilisme, cyclisme, athlétisme, yachting, aérostation, escrime, hippisme / dir. Henri Desgranges

14 septembre 19181918/09/14 (A19,N6445)

Distribution and morphology of knobs on the surface of parasitized RBCs.

<p>Atomic force micrographs (AFMs) of parasitized −α/αα (HE) (<b>a,d</b>) and −α/−α (HO) (<b>b,e</b>) RBCs obtained from naturally-parasitized Malian children with malaria and −/−α (HH) (<b>c,f</b>) RBCs infected with a laboratory-adapted <i>P. falciparum</i> clone showing normal (<b>a,b</b>) or abnormal (<b>c–f</b>) knob distributions and morphologies. AFM images are representative of 32, 10 and 18 images of parasites in −α/αα, −/−αα and −/−α RBCs. Inlays show YOYO-1-stained parasites that correspond to those imaged by AFM. Comparison AFMs of parasitized HbA, HbC and HbS RBCs have been reported previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037214#pone.0037214-Arie1" target="_blank">[22]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037214#pone.0037214-Cholera1" target="_blank">[37]</a>.</p

Relative cytoadherence and surface PfEMP1 levels of parasitized RBCs. a,

<p>Adherence of parasitized RBCs to MVECs. The numbers of parasitized −α/αα (HE), −α/−α (HO) and −/−α (HH) RBCs adhering to MVECs were normalized to those of parasitized αα/αα RBCs tested in parallel. The mean (± SEM) number of parasitized αα/αα RBCs per 100 MVECs was 260±40, <i>N</i> = 19. Results were obtained from 19 naturally-circulating parasite isolates and 2 laboratory-adapted parasite clones (A4tres and FCR-3), multiple blood donors (5 αα/αα, 2−α/αα, 2 −α/−α and 2−/−α), and 4 MVEC donors (not all combinations tested). This resulted in −α/αα, −α/−α and −/−α samples being compared to αα/αα samples 12, 5 and 4 times. <b>b,</b> Adherence of parasitized RBCs to monocytes. The numbers of parasitized −α/αα, −α/−α and −/−α RBCs adhering to monocytes were normalized to those of αα/αα RBCs tested in parallel. The mean (± SEM) number of parasitized αα/αα RBCs per 100 monocytes was 136±10, <i>N</i> = 12. Results were obtained from 3 naturally-circulating parasite isolates and 3 laboratory-adapted parasite clones (3D7, A4tres and FCR-3), multiple blood donors (5 αα/αα, 3 −α/αα, 2 −α/−α and 2−/−α) and 4 monocyte donors (not all combinations tested). This resulted in −α/αα, −α/−α and −/−α samples being compared to αα/αα samples 20, 3 and 4 times. The αα/αα and −α/αα RBCs were different from those used in endothelial cell adherence assays. <b>c,</b> PfEMP1 expression levels (median fluorescence intensities, MFI) on the surface of parasitized RBCs. The mean (± SEM) MFI of parasitized αα/αα RBCs was 556±153, <i>N</i> = 6. Results were obtained from 2 laboratory-adapted parasite clones (A4tres, FVO and FCR3^CSA), multiple blood donors (4 αα/αα, 6 −α/αα and 2−/−α), and various concentrations of 2 antisera (not all combinations tested). This resulted in −α/αα, and −/−α samples being compared to αα/αα samples 10 and 6 times. The αα/αα and −α/αα RBCs were different from those used in endothelial cell and monocyte adherence assays.</p

Effects of Age, Hemoglobin Type and Parasite Strain on IgG Recognition of <i>Plasmodium falciparum</i>–Infected Erythrocytes in Malian Children

<div><p>Background</p><p>Naturally-acquired antibody responses to antigens on the surface of <i>Plasmodium falciparum</i>-infected red blood cells (iRBCs) have been implicated in antimalarial immunity. To profile the development of this immunity, we have been studying a cohort of Malian children living in an area with intense seasonal malaria transmission.</p> <p>Methodology/Principal Findings</p><p>We collected plasma from a sub-cohort of 176 Malian children aged 3-11 years, before (May) and after (December) the 2009 transmission season. To measure the effect of hemoglobin (Hb) type on antibody responses, we enrolled age-matched HbAA, HbAS and HbAC children. To quantify antibody recognition of iRBCs, we designed a high-throughput flow cytometry assay to rapidly test numerous plasma samples against multiple parasite strains. We evaluated antibody reactivity of each plasma sample to 3 laboratory-adapted parasite lines (FCR3, D10, PC26) and 4 short-term-cultured parasite isolates (2 Malian and 2 Cambodian). 97% of children recognized ≥1 parasite strain and the proportion of IgG responders increased significantly during the transmission season for most parasite strains. Both strain-specific and strain-transcending IgG responses were detected, and varied by age, Hb type and parasite strain. In addition, the breadth of IgG responses to parasite strains increased with age in HbAA, but not in HbAS or HbAC, children.</p> <p>Conclusions/Significance</p><p>Our assay detects both strain-specific and strain-transcending IgG responses to iRBCs. The magnitude and breadth of these responses varied not only by age, but also by Hb type and parasite strain used. These findings indicate that studies of acquired humoral immunity should account for Hb type and test large numbers of diverse parasite strains.</p> </div

Increasing age and HbAS significantly protect Malian children against malaria.

<p>(A & B) The proportion of children who experienced at least one episode of malaria (malaria+) in the 2009 transmission season is shown. The children are categorized by age (A) or Hb type (B). (C & D) Survival analyses of the time to first malaria episode. Kaplan-Meier plots are shown for children grouped by age (C) or Hb type (D). Increasing age and HbAS were significantly associated with reduced malaria risk as measured by whether or not malaria was experienced (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060182#pone-0060182-g001" target="_blank">Figure 1A</a>, p<0.0001; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060182#pone-0060182-g001" target="_blank">Figure 1B</a>, p = 0.0203; chi-squared tests), or time to first malaria episode (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060182#pone-0060182-g001" target="_blank">Figure 1C</a>, p = 0.0002; <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060182#pone-0060182-g001" target="_blank">Figure 1D</a>, p = 0.0013; by log-rank tests).</p

Increases in merozoite antigen-specific IgG levels during a transmission season do not differ by Hb type.

<p>For each child, the change in IgG level from May to December 2009 was calculated for each antigen (A, AMA1-3D7; B, MSP1-3D7; C, EBA175-3D7; D, MSP2-3D7). All responses below the limit of detection (44 ELISA units) were assigned a value of 22 ELISA units. Median and interquartile range are shown. Positive values represent increases in IgG levels at the end of the transmission season. Changes in IgG levels were not significantly different among the three Hb types for any antigen (p>0.05 by Kruskal-Wallis tests).</p

Merozoite antigen-specific IgG levels do not decay during a dry season, regardless of Hb type.

<p>For each child, the change in IgG level from December 2009 to May 2010 was calculated for each antigen (A, AMA1-3D7; B, MSP1-3D7; C, EBA175-3D7; D, MSP2-3D7). All responses below the limit of detection (44 ELISA units) were assigned a value of 22 ELISA units. Median and interquartile range are shown. Positive values represent increases in IgG levels at the end of the dry season. Changes in IgG levels were not significantly different among the three Hb types for any antigen (p>0.05 by Kruskal-Wallis tests).</p

The breadth of IgG responses to parasite strains correlates with increased IgG titers to merozoite antigens.

<p>IgG titers to 4 merozoite antigens (AMA-1, EBA-175, MSP-1, MSP-2) were measured in plasma obtained before the transmission season, and stratified by the total number of parasite strains recognized by IgG. Tukey whisker plots are shown. IgG titers were compared using Kruskal-Wallis test followed by Dunn’s multiple comparison test. *p<0.05. The numbers of children recognizing 0-2, 3, 4, 5 and 6-7 parasite strains were 45, 34, 32, 36 and 30.</p

Breadth of IgG responses to parasite strains stratified by season, Hb type and age.

<p>The number of parasite strains (range, 0-7) recognized by IgG were counted and stratified by season, Hb type and age. <b>a</b>, Tukey whisker plots showing the total number of parasite strains recognized by IgG in paired plasma samples taken before and after the 2009 transmission season. p-values were calculated using Wilcoxon matched-pairs signed rank test. **p<0.01. <b>b</b>, <b>c</b>, Tukey whisker plots showing the total number of parasite strains recognized by IgG before (<b>b</b>) and after (<b>c</b>) the 2009 transmission season, stratified by age and Hb type. p-values were calculated using Kruskal-Wallis test followed by Dunn’s multiple comparison test. *p<0.05, **p<0.01, ***p<0.001.</p