The osmotic effectiveness of a large molecular weight glucose polymer fraction (Icodextrin) as a novel "colloid" osmotic agent in peritoneal dialysis was established, but the long-term safety remained undetermined. A randomized, controlled multicenter investigation of Icodextrin in ambulatory peritoneal dialysis (MIDAS) was undertaken to evaluate the long-term safety and efficacy by comparing daily overnight (8 to 12 hr dwell) use of isosmolar Icodextrin (282 mOsm/kg) with conventional 1.36% (346 mOsm/kg) and 3.86% (484 mOsm/kg) glucose exchanges over six months. Two hundred and nine patients were randomized from 11 centers, with 106 allocated to receive Icodextrin (D) and 103 to remain on glucose (control group; C); 138 patients completed the six month study (71 C, 67 D). All patients were divided into weak (1.36%) or strong (3.86%) subgroups based on their use of glucose solutions overnight during the pretreatment baseline period. The mean (+/- SEM) overnight ultrafiltration (UF) with D was 3.5 times greater than 1.36% glucose at eight hours [527 +/- 36 vs. 150 +/- 47 ml; 95% confidence interval (CI) for the difference +257 to +497 ml; P < 0.0001] and 5.5 times greater at 12 hours (561 +/- 44 vs. 101 +/- 48 ml, 95% CI for the difference +329 to +590; P < 0.0001) and no different from that of 3.86% glucose at eight hours (510 +/- 48 vs. 448 +/- 60 ml, 95% CI for the difference -102 to +226 ml; P = 0.44) and at 12 hours (552 +/- 44 vs. 414 +/- 78 ml, 95% CI for the difference -47 to +325 ml; P = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Background and objectives: Encapsulating peritoneal sclerosis (EPS) is a severe peritoneal fibrotic reaction in patients on long-term peritoneal dialysis (PD). The early clinical features may be nonspecific. The purpose of the study is to assess the reliability and diagnostic utility of abdominal CT scanning in the diagnosis of EPS.Design, setting, participants, & measurements: Abdominopelvic CT scans of 27 patients diagnosed with EPS on clinical and radiologic grounds in our unit from 1997 to 2006 were retrospectively analyzed. In addition, 35 control CT scans were scored: 15 from hemodialysis patients (HD controls) and 20 from patients on PD (PD controls). Scans were anonymized and scored independently by three radiologists.Results: Inter-rater agreement was moderate to very good (kappa ‫؍‬ 0.40 to 0.75) for peritoneal calcification, bowel distribution, bowel wall thickening, and bowel dilation but poorer for loculation of ascites and peritoneal thickening. There was a strongly significant difference between the total CT scan scores at EPS diagnosis and controls (P < 0.00001). Each individual parameter also showed significant differences between EPS and controls (P < 0.006). Bowel tethering and peritoneal calcification were the most specific parameters, and. loculation was the least discriminatory parameter. Interestingly, prediagnostic scans a median of 1.5 yr before EPS diagnosis were normal or near-normal in 9 of 13 EPS patients.Conclusions: CT scanning is a valid and reliable adjunct to the diagnosis of EPS but may not be useful as a screening tool, as the prediagnostic scans did not show abnormalities in many patients who subsequently developed EPS.

The human eosinophil differentiation factor (EDF) gene was cloned from a genomic library in A phage EMBL3A by using a murine EDF cDNA clone as a probe. The DNA sequence of a 3.2-kilobase BamHI fragment spanning the gene was determined. The gene contains three introns. The predicted amino acid sequence of 134 amino acids is identical with that recently reported for human interleukin 5 but shows no significant homology with other known hemopoietic growth regulators. The amino acid sequence shows strong homology (-70% identity) with that of murine EDF. Recombinant

Recombinant human interleukin-5 (rhIL-5), in either liquid or semi- solid cultures, selectively induced eosinophil production from normal human bone marrow, with no activity on other cell lineages. The time course of eosinophil production induced by murine IL-5, rhIL-3, and rh granulocyte-macrophage colony stimulating factor (GMCSF) was similar to rhIL-5. The rate of eosinophil maturation in vitro was independent of the stimulating cytokine, mature eosinophils being produced after 4 to 5 weeks in liquid culture with each of these cytokines. The eosinophils produced in response to each cytokine were morphologically indistinguishable, and had the ultrastructural features of maturity except that the electron-dense material in the granules had not formed into crystalline cores. Neither rhIL-1 nor rhIL-6 alone, or in combination with rhIL-5 or rhIL-3, induced eosinophil differentiation or proliferation under the conditions used. rhIL-3 and rhGMCSF induced more eosinophil colonies than rhIL-5, rhIL-5 had an additive, not synergistic, effect on eosinophil colony production when combined with either rhIL-3 or rhGMCSF, suggesting that rhIL-5 stimulates a smaller and possibly different population of eosinophil progenitors. However, rhIL-5 induced the greatest eosinophil production in liquid cultures, suggesting that although it may act on a smaller population of precursors, it is able to stimulate more proliferative steps than either rhIL-3 or rhGMCSF.

Following the observation that mouse interleukin 5 (IL5) is active as a B cell growth factor (BCGF) as well as an eosinophil differentiation factor, this work was carried out to test recombinant human IL5 for BCGF activity. A highly active, partially purified batch of recombinant human IL5 was prepared and tested for BCGF activity in four laboratories. This batch gave a 50% endpoint of 1:77,450 in the human eosinophil differentiation assay, 1:983 in the mouse eosinophil differentiation assay and 1:42 in the mouse BCL1 assay, thus demonstrating that, like mouse IL5, human IL5 has cross-species activity. By comparison with the assays in the mouse this batch would be expected to have 50% maximal human BCGF activity of about 1:4000. In each assay a known positive factor was used as a positive control, and there was no inhibitory activity in the preparation. However, despite the activity towards the mouse B cell lymphoma, the results showed no detectable activity in a panel of assays used to identify human BCGF and B cell differentiation factors. These assays included (a) proliferation assays with tonsillar or splenic B cells in the presence of the co-stimulators anti-mu or phorbol myristate acetate; (b) a restimulation assay in which tonsillar B cells are first activated with either Staphylococcus aureus Cowan 1 or a mixture of phorbol dibutyrate and ionomycin, or splenic B cells are first activated with anti-mu; (c) production of immunoglobulin by B cells in a restimulation assay with Staphylococcus aureus Cowan 1; (d) production of immunoglobulin by the Epstein-Barr virus-transformed B lymphoblastoid CESS cell line; (e) the ability to stimulate proliferation of chronic lymphocytic leukemia (B-CLL) cells freshly explanted from three different patients; (f) the ability to stimulate the B lymphoma (L4) cell line and the mature B cell (HBF1) line, and (g) the ability to replace T cells in specific antibody responses. It therefore seems unlikely that recombinant human IL5 is either a growth or a differentiation factor for human B cells, and raises the interesting question of the biological significance of the BCGF activity of this factor in the mouse.