Selection of an optimal culture medium and the most responsive viability assay to assess AgNPs toxicity with primary cultures of Eisenia fetida coelomocytes.

Earthworm immune cells (coelomocytes) have become a target system in ecotoxicology due to their sensitivity against a wide range of pollutants, including silver nanoparticles (AgNPs). Presently, in vitro approaches (viability assays in microplate, flow cytometry, cell sorting) with primary cultures of Eisenia fetida coelomocytes have been successfully used to test the toxicity and the dissimilar response of cell subpopulations (amoebocytes and eleocytes) after PVP-PEI coated AgNPs and AgNO3 exposures. In order to obtain reliable data and to accurately assess toxicity with coelomocytes, first an optimal culture medium and the most responsive assay were determined. AgNPs posed a gradual decrease in coelomocytes viability, establishing the LC50 value in RPMI-1640 medium at 6 mg/l and discarding that the observed cytotoxicity was attributable to its coating agent PVP-PEI. Exposure to AgNPs caused selective cytotoxicity in amoebocytes, which correlated with the Ag concentrations measured in sorted amoebocytes and reinforced the idea of dissimilar sensitivities among amoebocytes and eleocytes. Silver nano and ionic forms exerted similar toxicity in coelomocytes. The in vitro approaches with coelomocytes of E. fetida performed in this study have the capacity to predict impairments caused by pollutants at longer exposure levels and thus, provide rapid and valuable information for eco(nano)toxicology.

Innovative in vivo and in vitro bioassays for the establishment of toxicity thresholds of pollutants in sediment quality assessment using polychaetes and their immune cells.

Sediment toxicity testing has become a crucial component for assessing the risks posed by contaminated sediments and for the development of sediment quality assessment strategies. Commonly used organisms for bioassays with estuarine sediments include amphipods, Arenicola marina polychaetes and echinoids. Among the latter, the Sea Urchin Embryo test (SET) is the most widely used. However, one relevant limitation of this bioassay is the unavailability of gametes all year-round, particularly outside the natural spawning seasons. Consequently, the establishment of an appropriate and complementary model organism for a continuous assessment of sediment quality is recommended. A reliable assessment of the hazards resulting from pollutants in sediments or pore water, can be achieved with ecologically relevant species of sediment such as the polychaete Hediste diversicolor, which is widespread in estuaries and has the capacity to accumulate pollutants. The aim of this work was to develop reliable in vivo and in vitro bioassays with H. diversicolor and its coelomocytes (immune cells) to determine the toxicity thresholds of different contaminants bounded to sediments or resuspended into water. Polychaetes were exposed to sublethal concentrations of CuCl2 (in vivo) and a non-invasive method for collection of polychaetes coelomocytes was applied for the in vitro bioassay, exposing cells to a series of CuCl2 and AgNPs concentrations. Same reference toxicants were used to expose Paracentrotus lividus following the SET (ICES Nº 51; Beiras et al., 2012) and obtained toxicity thresholds were compared between the two species. In vivo exposure of polychaetes to high concentrations of Cu produced weight loss and histopathological alterations. After in vitro approaches, a significant decrease in coelomocytes viability was recorded for both toxicants, in a monotonic dose-response curve, at very short-exposure times (2 h). The toxicity thresholds obtained with polychaetes were in line with the ones obtained with the SET, concluding that their sensitivity is similar. In conclusion, in vivo and in vitro bioassays developed with H. diversicolor are accurate toxicity screenings of pollutants that could be bounded to sediments or dissolved in the pore water, and may complement the SET outside the spawning period of the echinoderms. The bioassays herein developed could be applied not only to establish the toxicity thresholds of individual compounds or mixtures, but also to assess the toxicity of field collected sediments.

Mail and Telephone Outreach from Electronic Health Records for Research Participation on Cognitive Health and Aging.

OBJECTIVES: This report describes the efficacy and utility of recruiting older individuals by mail to participate in research on cognitive health and aging using Electronic Health Records (EHR). METHODS: Individuals age 65 or older identified by EHR in the Mount Sinai Health System as likely to have Mild Cognitive Impairment (MCI) were sent a general recruitment letter (N=12,951). A comparison group of individuals with comparable age and matched for gender also received the letter (N=3,001). RESULTS: Of the 15,952 individuals who received the mailing, 953 (6.0%) responded. 215 (1.3%) declined further contact. Overall rate of expression of interest was 4.6%. Of the 738 individuals who responded positively to further contact, 321 indicated preference for further contact by telephone. Follow-up of these individuals yielded 30 enrollments (0.2% of 15,952). No differences in response rate were noted between MCI and comparison groups, but the comparison group yielded higher enrollment. 6 individuals who were not the intended recipients of mailing but nevertheless contacted our study were also enrolled. CONCLUSIONS: Mailings to individuals identified through a trusted source, such as a medical center from which they have received clinical care, may be a viable means of reaching individuals within this age group as this effort yielded a low rejection rate. However, EHR information did not enhance study enrollment. Implications for improving recruitment are discussed.

Chronic hepatitis C infection: An independent risk factor for subclinical atheromatosis. / Infección crónica por el virus de la hepatitis C: un factor de riesgo independiente para la ateromatosis subclínica.

BACKGROUND: The association between subclinical atheromatosis and chronic hepatitis C virus (HCV) infection is unknown but is relevant now that antivirals are improving the survival of patients with the infection. OBJECTIVES: To determine whether HCV is an independent risk factor for subclinical atheromatosis and to analyse the changes in lipid profiles according to viral RNA levels and hepatic fibrosis. PATIENTS AND METHODS: We conducted an observational, cross-sectional study that included 102 HCV-positive patients and 102 HCV-negative patients with parity in terms of sex and age, with no history of cardiovascular or kidney disease or diabetes. Atheromatosis (the presence of atheromatous plaques) and the carotid intima-media thickness (CIMT) were assessed using ultrasonography of the carotid and femoral arteries. RESULTS: There was a greater presence of atheromatosis in any vascular territory in HCV-positive patients than in the patients without infection (58.8% vs. 28.4%, p<.0001). In the multivariate analysis, the factors significantly associated with atheromatosis included HCV infection (OR, 14.37 [5.5-37.3]; p<.001), age (OR, 1.12 [1.1-1.2]; p<.001), male sex (OR, 4.32 [1.9-9.5]; p<.001) and the triglyceride/HDL cholesterol coefficient (TG/HDL-indirect indicator of insulin resistance) (OR, 1.34 [1.1-1.6]; p=.007). The HCV-positive patients with atheromatous plaques had a higher TG/HDL coefficient but no significant differences in terms of the viral load or degree of hepatic fibrosis and with a 'low risk' lipid profile. CONCLUSIONS: HCV infection is an independent risk factor for subclinical atheromatosis. Systemic arterial ultrasonography for this population improves the cardiovascular risk assessment beyond lipid profile abnormalities and the risk calculation using SCORE tables.

GLIM criteria for the diagnosis of malnutrition - A consensus report from the global clinical nutrition community.

RATIONALE: This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. METHODS: In January 2016, the Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. GLIM appointed a core leadership committee and a supporting working group with representatives bringing additional global diversity and expertise. Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications. RESULTS: A two-step approach for the malnutrition diagnosis was selected, i.e., first screening to identify "at risk" status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among the GLIM core and supporting working group members. The top five ranked criteria included three phenotypic criteria (non-volitional weight loss, low body mass index, and reduced muscle mass) and two etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least one phenotypic criterion and one etiologic criterion should be present. Phenotypic metrics for grading severity as Stage 1 (moderate) and Stage 2 (severe) malnutrition are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories. CONCLUSION: A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure further collaboration and endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The diagnostic construct should be re-considered every 3-5 years.

GLIM criteria for the diagnosis of malnutrition - A consensus report from the global clinical nutrition community.

RATIONALE: This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. METHODS: In January 2016, the Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. GLIM appointed a core leadership committee and a supporting working group with representatives bringing additional global diversity and expertise. Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications. RESULTS: A two-step approach for the malnutrition diagnosis was selected, i.e., first screening to identify "at risk" status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among the GLIM core and supporting working group members. The top five ranked criteria included three phenotypic criteria (weight loss, low body mass index, and reduced muscle mass) and two etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least one phenotypic criterion and one etiologic criterion should be present. Phenotypic metrics for grading severity as Stage 1 (moderate) and Stage 2 (severe) malnutrition are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories. CONCLUSION: A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure further collaboration and endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The diagnostic construct should be re-considered every 3-5 years.

Integrative assessment of the effects produced by Ag nanoparticles at different levels of biological complexity in Eisenia fetida maintained in two standard soils (OECD and LUFA 2.3).

There is a potential risk to increase the release of silver nanoparticles (Ag NPs) into the environment: For instance. in soils receiving sludge models estimate 0.007 mg Ag NPs kg-1 that will annually increase due to sludge or sludge incineration residues land-disposal. Thus, the concern about the hazards of nanosilver to soils and soil invertebrates is growing. Studies performed up to now have been focused in traditional endpoints, used limit range concentrations and employed different soil types that differ in physico-chemical characteristics. Presently, effects of Ag NPs have been measured at different levels of biological complexity in Eisenia fetida, exposed for 3 and 14 d to high but sublethal (50 mg Ag NPs kg-1) and close to modeled environmental concentrations (0.05 mg Ag NPs kg-1). Since characteristics of the exposure matrix may limit the response of the organisms to these concentrations, experiments were carried out in OECD and LUFA soils, the most used standard soils. High concentrations of Ag NPs increased catalase activity and DNA damage in OECD soils after 14 d while in LUFA 2.3 soils produced earlier effects (weight loss, decrease in cell viability and increase in catalase activity at day 3). At day 14, LUFA 2.3 (low clay and organic matter-OM-) could have provoked starvation of earthworms, masking Ag NPs toxicity. The concentration close to modeled environmental concentrations produced effects uniquely in LUFA 2.3 soil. Accurate physico-chemical characteristics of the standard soils are crucial to assess the toxicity exerted by Ag NPs in E. fetida since low clay and OM contents can be considered toxicity enhancers.

[Magnetic resonance imaging without sedation in neonates]. / Resonancia magnética sin sedación en recién nacidos.

INTRODUCTION: The ability to perform magnetic resonance imaging (MRI) without sedation in the neonatal period increases patient safety, availability and profitability of the diagnostic tool. The aim in this study was to evaluate a new protocol of MRI without sedation during a 20-month period. In the protocol, the patients are prepared in the neonatal unit. PATIENTS AND METHOD: Prospective descriptive study, from May 2012 to December 2013. Patients included were neonates requiring MRI, clinically stable and not requiring ventilatory support. The method was based on the application of developmental centered care and the use of a vacuum matress to immobilize the baby. The principal outcome parameter of interest was the percentage of succesfully completed MRIs. The duration of the MRI and the number of interruptions, was also studied from October 2012. RESULTS: A total of 43 MRIs without sedation were carried out on 42 patients: 41 cerebral and 2 spinal. The success rate was 97.7% (42/43). The mean MRI time was 26.3 minutes (95% CI 23.3-29.3 mins; range 16-50 mins). MRIs were completed without interruption in 20 of the 34 cases (58%) in which the duration was recorded. The number of interruptions per procedure varied from 0 to 3, with a mean of 0.6 (95% CI 0.3-0.8) and a median of 0. CONCLUSION: The protocol had a success rate of over 90%. Thus MRI without sedation seems applicable in Spanish hospitals, with most of the preparation being performed in the neonatal unit, in order to reduce the occupation of the MRI unit, as well as minimizing stress to the baby.

Role of two conserved glycine residues in the beta-propeller domain of the integrin alpha4 subunit in VLA-4 conformation and function.

The N-terminal region of the alpha integrin subunits is predicted to fold into a beta-propeller domain. Using K562 alpha4 transfectants we show that mutations at alpha4 subunit residues Gly130 and Gly190 affect the conformation of this domain causing a reduction in the recognition of alpha4 by anti-alpha4 antibodies which map to the beta-propeller. The improper alpha4 conformation also led to an altered association with the beta1 subunit, and to a lack of alpha4beta1 adhesion to VCAM-1 and CS-1/fibronectin, as well as an abolishment of anti-alpha4- and anti-beta1-dependent homotypic aggregation. The total conservation of Gly130 and Gly190 among integrin alpha subunits suggests their importance in the correct folding of their respective beta-propeller domains, and thus, in the adhesive activity of the integrins.

Localization of the lipid receptors CD36 and CLA-1/SR-BI in the human gastrointestinal tract: towards the identification of receptors mediating the intestinal absorption of dietary lipids.

The scavenger receptors CLA-1/SR-BI and CD36 interact with native and modified lipoproteins and with some anionic phospholipids. In addition, CD36 binds/transports long-chain free fatty acids. Recent biochemical evidences indicates that the rabbit CLA-1/SR-BI receptor can be detected in enterocytes, and previous studies showed the presence of mRNA for both CLA-1/SR-BI and CD36 in some segments of the intestinal tract. These findings prompted us to study their respective localization and distribution from the human stomach to the colorectal segments, using immunohistochemical methods. Their expression in the colorectal carcinoma-derived cell line Caco-2 was analyzed by Northern blotting. In the human intestinal tract, CLA-1/SR-BI was found in the brush-border membrane of enterocytes from the duodenum to the rectum. However, CD36 was found only in the duodenal and jejunal epithelium, whereas enterocytes from other intestinal segments were not stained. In the duodenum and jejunum, CD36 co-localized with CLA-1/SR-BI in the apical membrane of enterocytes. The gastric epithelium was immunonegative for both glycoproteins. We also found that CLA-1/SR-BI mRNA was expressed in Caco-2 cells and that its expression levels increased concomitantly with their differentiation. In contrast, the CD36 transcript was not found in this colon cell line, in agreement with the absence of this protein in colon epithelium. The specific localization of CLA-1/SR-BI and CD36 along the human gastrointestinal tract and their ability to interact with a large variety of lipids strongly support a physiological role for them in absorption of dietary lipids.

Surgical treatment of high gastric ulcer.

The purpose of this study has been to review the late results of surgical treatment of 244 patients with endoscopically proved benign chronic gastric ulcer located 5 cm or less from the cardia. In five patients, a total gastrectomy with esophagojejunostomy was performed. Proximal gastrectomy was used in 3 patients, mesogastrectomy in 5 patients, a partial Schoemaker's procedure in 73 patients, Pauchet's procedure in 70 patients, and Csendes' procedure in 23 patients. Nonresective procedures were employed in 67 patients and included the Kelling-Madlener procedure in 23 patients, pyloroplasty alone in 10 patients, gastrojejunostomy alone in 4 patients, local or wedge excision of the ulcer in 9 patients, and vagotomy and pyloroplasty in 21 patients. The follow-up evaluation was performed in 91 percent of the patients (mean 9 years postoperatively, range 5 to 15 years), with emptying endoscopy in all nonresected patients. A high mortality was observed after total or proximal gastrectomy, as well as after nonresective procedures. After the other resective techniques, low postoperative morbidity and mortality were observed. No recurrent ulcer was seen after the resective procedures. Based on these results, we propose that when the ulcer is located 5 cm below the cardia, Schoemaker's or Pauchet's procedure should be performed; if the ulcer is located 2 cm or less from the cardia, Csendes' procedure or the Kelling-Madlener procedure should be employed.

The effect of the dosage of steroids on the incidence of cytomegalovirus infections in renal transplant recipients.

In a retrospective survey of 92 cadaver renal transplant recipients, cytomegalovirus (CMV) infections were detected in 23 of 34 (68 per cent) patients treated with high doses of steroids but in only 27 of 58 (47 per cent) patients given low doses. Pretransplant blood transfusions were associated with both an improvement in one-year allograft survival-rates (P less than 0.05) and an increase in the incidence of CMV infections. When standardised for any transfusion effect, the incidence of CMV infections was significantly higher in those patients given high doses of steroids (P less than 0.05). In the same group of patients, moreover, CMV infections were associated with a statistically significant increase in the renal allograft survival-rate (P = 0.03).

Whole-body protein kinetics in elective surgical patients receiving peptide or amino acid solutions.

We compared the efficacy of two enteral solutions that were isonitrogenous and of identical amino acid composition but differed in that one solution contained only free amino acids whereas the other contained a mixture of free amino acids and peptides. Protein kinetics and nitrogen balance were evaluated in a group of six elective surgical patients. Primed-constant infusion with 15N-glycine was started 24h after gynecologic surgery and sustained over 3 days. During the first postoperative day, patients received enteral 0.45% saline. During postoperative days two and three, the patients received either the free amino acid solution or the mixture of peptides and free amino acids in a crossover design. There were no differences in protein kinetics or nitrogen balance with the two treatments.

Influence of polymeric enteral nutrition supplemented with different doses of glutamine on gut permeability in critically ill patients.

OBJECTIVES: To evaluate the effect of glutamine-supplemented polymeric enteral formulas on the recovery of gut-permeability abnormalities in critically ill patients. METHODS: Twenty-three patients were randomized to receive a conventional casein-based enteral formula (ADN), ADN plus glutamine in a dose of 0.15 g x kg(-1) x d(-1) or ADN plus 0.30 g x kg(-1) x d(-1) of glutamine for 8 d. The lactulose mannitol permeability test (L/M) was performed at baseline and at the end of the study. Nineteen healthy volunteers served as controls for the L/M test. RESULTS: An increase in permeability compared with control subjects was observed in patients at baseline (mean +/- standard error of the mean; L/M ratio: 0.11 +/- 0.03 and 0.025 +/- 0.004, respectively; P < 0.02). The L/M ratio improved after the period of enteral nutrition as a whole (initial L/M: 0.11 +/- 0.03, final L/M: 0.061 +/- 0.01; P < 0.03), but no difference was found between groups. CONCLUSIONS: Even though polymeric enteral nutrition was associated with a significant improvement in the L/M ratio, glutamine supplementation did not show a specific influence in improving recovery of gut permeability in critically ill patients.

Comparison of three methods for the estimation of total nitrogen losses in hospitalized patients.

Since the measurement of total nitrogen output (TNO) is not routinely determined in the clinical setting, its level is frequently estimated using formulas based on the urinary urea nitrogen excretion (UUN). We measured TNO in 124 surgical patients over 990 days (TNO, 19.22 +/- 8.72 g N/day; total urinary nitrogen (TUN) 18.17 +/- 8.70 g N/day; UUN, 15.17 +/- 7.70 g N/day; mean gastrointestinal nitrogen (MGIN) 0.68 +/- 0.49 g N/day; integumental nitrogen (ITGN), 0.34 +/- 0.08 g N/day) and compared the results with the daily estimations using three different formulas: formula A, UUN + 4; formula B, UUN x 1.20 + 1.05, where 1.20 is the reciprocal of the mean ratio UUN/TUN and 1.05 the mean extraurinary nitrogen losses; and formula C, UUN x 1.0986 + 2.55, derived from the regression analysis of UUN vs TNO. TNO estimated by these formulas were 19.17 +/- 7.70, 19.26 +/- 9.24, and 19.22 +/- 8.70 g N/day, respectively. The regression analyses of the estimated TNO from the three formulas versus the measured TNO indicated that formulas A, B and C were equally accurate in estimating TNO over the entire range of UUN. However, when only values of UUN greater than or equal to 30 g N were considered, a modified formula A (UUN + 6) was the best predictor of TNO. Daily audits of the differences between the estimated and measured TNO showed comparable results for the three formulas. In 28.4 to 31.1% of the observed days the differences were higher than +/- 2 g N/day, an error which is not acceptable when estimating the protein requirements in many clinical conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Gut mucosal atrophy after a short enteral fasting period in critically ill patients.

PURPOSE: The purpose of this study was to evaluate the presence of gut mucosal atrophy and changes in mucosal permeability in critically ill patients after a short fasting period. MATERIALS AND METHODS: Fifteen critically ill patients underwent a period of enteral fasting of at least 4 days (mean 7.8 days). We took the following measurements the day before initiating enteral nutrition: indirect calorimetry, serum albumin, prealbumin, and lymphocyte count. We also performed a duodenal endoscopic biopsy with histopathological and mucosal morphometric analysis including villus height and crypt depth. The lactulose-mannitol test was performed to assess gut permeability. A total of 28 healthy volunteers served as controls for duodenal biopsy or lactulose-mannitol test. Clinical data, such as length of fasting, severity score, and previous parenteral nutritional support, were recorded. RESULTS: We found gut mucosal atrophy, expressed as a decrease in villus height and crypt depth, in patients compared with controls. The patients also exhibited an abnormal lactulose-mannitol test. Morphometric changes did not correlate with permeability. Further, we found no correlation between the results of the lactulose-mannitol test and of mucosal morphometry with clinical data. CONCLUSIONS: We found that a short period of enteral fasting was associated with significant duodenal mucosal atrophy and abnormal gut permeability in critically ill patients.

Antineutrophil cytoplasmic antibody-associated necrotizing crescentic glomerulonephritis in a patient receiving treatment with etanercept for severe rheumatoid arthritis.

Etanercept is a tumor necrosis factor inhibitor used in the treatment of rheumatoid arthritis and, increasingly, in a range of other diseases. We report a case of necrotizing crescentic glomerulonephritis, associated with a positive antineutrophil cytoplasmic antibody, causing acute renal failure in a woman receiving treatment with etanercept for severe rheumatoid arthritis. Our patient was treated with steroids and cyclophosphamide following withdrawal of etanercept, with a good clinical response. Although reports of vasculitis in patients receiving treatment with etanercept are rare, this drug has been shown to up-regulate some aspects of immune function, and the possibility that this agent may precipitate or exacerbate vasculitis in some individuals has to be considered.

The effect of hemodialysis, vitamin D metabolites and renal transplantation on the skeletal demineralization associated with renal osteodystrophy: a computerized histomorphometric analysis.

Twenty-three patients with end-stage renal failure treated by hemodialysis or transplantation were followed for up to 10 years. Sequential full thickness iliac crest bone biopsies were obtained to assess the effects on bone disease of hemodialysis, treatment with 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and 24,25-dihydroxycholecalciferol [24,25-(OH)2D3] and renal transplantation. The biopsies were analyzed by a computerized histomorphometric technique which allowed accurate measurements of calcified bone and osteoid areas. Serum aluminum and parathyroid hormone concentrations were also monitored. Hemodialysis was associated with a loss of calcified bone and an increase in osteoid areas. The progressive bone loss was arrested but not reversed following treatment with either 1,25-(OH)2D3 or 24,25-(OH)2D3. Osteoid area was unchanged or reduced following treatment with 1,25-(OH)2D3 in all but three patients who had serum aluminum concentrations in excess of 5 mumol/l. 24,25-(OH)2D3 was not effective in reducing osteoid area, and combined treatment with 1,25 and 24,25-(OH)2D3 had no effect beyond that expected with 1,25-(OH)2D3 alone. Bone biopsies showed loss of calcified bone and an increase in osteoid areas one year and more after successful renal transplantation in five patients. Nineteen of the 23 patients developed serum aluminum concentrations greater than 3 mumol/l, probably because of the use of oral aluminum hydroxide as a phosphate binding agent. In these patients serum parathyroid hormone concentrations greater than 600 pg/ml appeared to prevent the development of osteopenia.