https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.22759

Diagnosis, management, and treatment of hepatitis C: An update

Background Cardiovascular disease is common in older adults with end-stage renal disease who are undergoing regular dialysis, but little is known about the prevalence and extent of cardiovascular disease in children and young adults with end-stage renal disease. Methods We used electron-beam computed tomography (CT) to screen for coronary-artery calcification in 39 young patients with end-stage renal disease who were undergoing dialysis (mean [±SD] age, 19±7 years; range, 7 to 30) and 60 normal subjects 20 to 30 years of age. In those with evidence of calcification on CT scanning, we determined its extent. The results were correlated with the patients' clinical characteristics, serum calcium and phosphorus concentrations, and other biochemical variables. Results None of the 23 patients who were younger than 20 years of age had evidence of coronary-artery calcification, but it was present in 14 of the 16 patients who were 20 to 30 years old. Among those with calcification, the mean calcification score was ...

Coronary-Artery Calcification in Young Adults with End-Stage Renal Disease Who Are Undergoing Dialysis

Mortality rates in ESRD are unacceptably high. Disorders of mineral metabolism (hyperphosphatemia, hypercalcemia, and secondary hyperparathyroidism) are potentially modifiable. For determining associations among disorders of mineral metabolism, mortality, and morbidity in hemodialysis patients, data on 40,538 hemodialysis patients with at least one determination of serum phosphorus and calcium during the last 3 mo of 1997 were analyzed. Unadjusted, case mix-adjusted, and multivariable-adjusted relative risks of death were calculated for categories of serum phosphorus, calcium, calcium x phosphorus product, and intact parathyroid hormone (PTH) using proportional hazards regression. Also determined was whether disorders of mineral metabolism were associated with all-cause, cardiovascular, infection-related, fracture-related, and vascular access-related hospitalization. After adjustment for case mix and laboratory variables, serum phosphorus concentrations >5.0 mg/dl were associated with an increased relative risk of death (1.07, 1.25, 1.43, 1.67, and 2.02 for serum phosphorus 5.0 to 6.0, 6.0 to 7.0, 7.0 to 8.0, 8.0 to 9.0, and >/=9.0 mg/dl). Higher adjusted serum calcium concentrations were also associated with an increased risk of death, even when examined within narrow ranges of serum phosphorus. Moderate to severe hyperparathyroidism (PTH concentrations >/=600 pg/ml) was associated with an increase in the relative risk of death, whereas more modest increases in PTH were not. When examined collectively, the population attributable risk percentage for disorders of mineral metabolism was 17.5%, owing largely to the high prevalence of hyperphosphatemia. Hyperphosphatemia and hyperparathyroidism were significantly associated with all-cause, cardiovascular, and fracture-related hospitalization. Disorders of mineral metabolism are independently associated with mortality and morbidity associated with cardiovascular disease and fracture in hemodialysis patients.

Mineral Metabolism, Mortality, and Morbidity in Maintenance Hemodialysis

Background Anemia, a common complication of chronic kidney disease, usually develops as a consequence of erythropoietin deficiency. Recombinant human erythropoietin (epoetin alfa) is indicated for the correction of anemia associated with this condition. However, the optimal level of hemoglobin correction is not defined. Methods In this open-label trial, we studied 1432 patients with chronic kidney disease, 715 of whom were randomly assigned to receive a dose of epoetin alfa targeted to achieve a hemoglobin level of 13.5 g per deciliter and 717 of whom were assigned to receive a dose targeted to achieve a level of 11.3 g per deciliter. The median study duration was 16 months. The primary end point was a composite of death, myocardial infarction, hospitalization for congestive heart failure (without renal replacement therapy), and stroke. Results A total of 222 composite events occurred: 125 events in the high-hemoglobin group, as compared with 97 events in the low-hemoglobin group (hazard ratio, 1.34; 95% confidence interval, 1.03 to 1.74; P = 0.03). There were 65 deaths (29.3%), 101 hospitalizations for congestive heart failure (45.5%), 25 myocardial infarctions (11.3%), and 23 strokes (10.4%). Seven patients (3.2%) were hospitalized for congestive heart failure and myocardial infarction combined, and one patient (0.5%) died after having a stroke. Improvements in the quality of life were similar in the two groups. More patients in the high-hemoglobin group had at least one serious adverse event. Conclusions The use of a target hemoglobin level of 13.5 g per deciliter (as compared with 11.3 g per deciliter) was associated with increased risk and no incremental improvement in the quality of life. (ClinicalTrials.gov number, NCT00211120.)

https://www.nejm.org/doi/pdf/10.1056/NEJMoa065485

Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease

Background Cardiovascular disease is common in older adults with end-stage renal disease who are undergoing regular dialysis, but little is known about the prevalence and extent of cardiovascular disease in children and young adults with end-stage renal disease. Methods We used electron-beam computed tomography (CT) to screen for coronary-artery calcification in 39 young patients with end-stage renal disease who were undergoing dialysis (mean [±SD] age, 19±7 years; range, 7 to 30) and 60 normal subjects 20 to 30 years of age. In those with evidence of calcification on CT scanning, we determined its extent. The results were correlated with the patients’ clinical characteristics, serum calcium and phosphorus concentrations, and other biochemical variables. Results None of the 23 patients who were younger than 20 years of age had evidence of coronary-artery calcification, but it was present in 14 of the 16 patients who were 20 to 30 years old. Among those with calcification, the mean calcification score was 1157± 1996, and the median score was 297. By contrast, only 3 of the 60 normal subjects had calcification. As compared with the patients without coronary-artery calcification, those with calcification were older (26±3 vs. 15±5 years, P<0.001) and had been undergoing dialysis for a longer period (14±5 vs. 4±4 years, P< 0.001). The mean serum phosphorus concentration, the mean calcium–phosphorus ion product in serum, and the daily intake of calcium were higher among the patients with coronary-artery calcification. Among 10 patients with calcification who underwent followup CT scanning, the calcification score nearly doubled (from 125±104 to 249±216, P=0.02) over a mean period of 20±3 months. Conclusions Coronary-artery calcification is common and progressive in young adults with end-stage renal disease who are undergoing dialysis. (N Engl J Med 2000;342:1478-83.)

/pdf/coronary-artery-calcification-in-young-adults-with-end-stage-4clow3rb3g.pdf

Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis

An adult recipient of an HLA-DR, DQ-mismatched, T cell-depleted bone marrow graft, who remains without graft versus host disease and who is not maintained on immunosuppressive therapy, was studied at 23 months posttransplantation for in vitro reactivity against the mismatched antigens of the host. The donor's PBMC's proliferated vigorously against the recipient's stimulators in the pretransplant mixed lymphocyte cultures (MLC). After transplant reconstitution, MLCs demonstrated that the in vitro response of engrafted donor T cells against host MHC class II antigens was equivalent to control allogeneic responses, while there was no detectable response against the donor's antigens. Posttransplantation limiting dilution analysis showed no difference between the precursor frequencies of antihost responders among populations of fresh donor PBMCs and among the engrafted cells of donor origin that are found circulating in the patient. This result suggests that clonal deletion is, at best, incomplete and that peripheral tolerance is essential in protecting this patient from GVHD. These findings also support the conclusion that bone marrow-derived thymic elements may be important for clonal deletion in human chimeras.

In Vitro Alloreactivity Against Host Antigens In An Adult Hla-mismatched Bone Marrow Transplant Recipient Despite In Vivo Host Tolerance

It has been thought that the dermatitis caused by pollen and experimentally reproducible by cutaneous testing with pollen oil, is due to the presence in the oil of the atopic excitant. We have been able to show that the dermatitis is not due to the atopic excitant but to the oil itself. Hypersensitiveness to the pollen oil occurs in 15 per cent of hay fever subjects, in 15 per cent of atopic persons not subject to hay fever and in 15 per cent of nonatopic persons. It is thus to be classified as a contact dermatitis similar in its nature to dermatitis due to poison ivy, sumac and primrose. The results of this investigation naturally suggest a similar differentiation of the excitant of atopy and of dermatitis in other materials, and it is obvious that this principle must be important to the diagnosis and also to the treatment of dermatitis caused by materials containing atopic excitants.

Studies in Contact Dermatitis: I. The Nature and Etiology of Pollen Dermatitis Preliminary Report

https://www.gastrojournal.org/article/S0016-5085(14)60289-4/pdf

Edgar L. Milford

Papers

In Vitro Alloreactivity Against Host Antigens In An Adult Hla-mismatched Bone Marrow Transplant Recipient Despite In Vivo Host Tolerance

Studies in Contact Dermatitis: I. The Nature and Etiology of Pollen Dermatitis Preliminary Report

363 Human Hematopoietic Stem Cells With a Defined Immunodeficiency and Enteropathy Transfer Clinical Phenotype to a Novel Humanized Mouse Strain

MLR-reactive thymocytes in the rat: Ia-positive stimulator and Ia-negative responder cells.

AbstractDegalon bead columns for rapid B and T cell separation