The impact of sickle cell trait on glycated haemoglobin in diabetes mellitus.

AIMS: To determine the effect of sickle cell trait on measurement of glycated haemoglobin (HbA(1c)) in African American patients with diabetes mellitus. METHODS: This is a retrospective study including 885 outpatients who underwent HbA(1c) testing. Medical record review and sickle cell trait determinations based on the HbA(1c) assay were performed in African American participants. The relationship between HbA(1c) and serum glucose measurements was analysed. RESULTS: Data were obtained from 385 AA (109 with SCT, 22 with haemoglobin C trait and 254 without haemoglobinopathy) and 500 European American patients. In a model created through multivariate repeated-effects regression, the relationship between HbA(1c) and simultaneous serum glucose did not differ between African American subjects with and without the sickle cell trait, but differed between African American subjects without the sickle cell trait and European Americans (P = 0.0002). CONCLUSIONS: Sickle cell trait does not impact the relationship between HbA(1c) and serum glucose concentration. In addition, it does not appear to account for ethnic difference in this relationship between African Americans and whites.

Comparison of glycated albumin and hemoglobin A(1c) levels in diabetic subjects on hemodialysis.

Glycated albumin is thought to more accurately reflect glycemic control in diabetic hemodialysis patients than hemoglobin A(1c) because of shortened red cell survival. To test this, glycated hemoglobin and albumin levels were measured in blood samples collected from 307 diabetic subjects of whom 258 were on hemodialysis and 49 were without overt renal disease. In diabetic subjects with renal disease, relative to those without, the mean serum glucose and glycated albumin concentrations were significantly higher while hemoglobin A(1c) tended to be lower. The glycated albumin to hemoglobin A(1c) ratio was significantly increased in dialysis patients compared with the controls. Hemoglobin A(1c) was positively associated with hemoglobin and negatively associated with the erythropoietin dose in hemodialysis patients, whereas these factors and serum albumin did not significantly impact glycated albumin levels. Using best-fit multivariate models, dialysis status significantly impacted hemoglobin A(1c) levels without a significant effect on glycated albumin. Our results show that in diabetic hemodialysis patients, hemoglobin A(1c) levels significantly underestimate glycemic control while those of glycated albumin more accurately reflect this control.

Efficacy and safety of gemtuzumab ozogamicin in patients with poor-prognosis acute myeloid leukemia.

The objective of this work was to determine the safety and efficacy of gemtuzumab ozogamicin in patients with poor prognosis acute myeloid leukemia (AML). Patients with the following diagnoses/characteristics were treated with 1-3 infusions of gemtuzumab ozogamicin at a dose of 9 mg/m2: (1) relapse of AML < or = 6 months of first complete remission (CR); (2) AML refractory to chemotherapy at initial induction or at first relapse; (3) AML in second or greater relapse; (4) myeloid blast crisis of chronic myeloid leukemia (CML); (5) untreated patients > or = 70 years or > or = 55 years with abnormal cytogenetics (excluding inv 16, t(15;17) and t(8;21)) and/or an antecedent hematologic disorder; (6) refractory anemia with excess blasts in transformation (RAEBT). Forty-three patients, ages 19-84 (mean 62), were treated, including 7 patients with untreated AML age > 70 years, 2 with untreated RAEBT, 14 with AML first salvage (first remission 0-6 months), 15 with AML > or = second salvage and 14 with myeloid blast phase of CML. The overall response rate was 14%, with 4/43 (9%) patients achieving CR and 2/43 (5%) achieving CR without platelet recovery. The most significant toxicity was neutropenic fever, which occurred in 84% of patients. In conclusion, in patients with relapsed/refractory AML, gemtuzumab ozogamicin has a comparable response rate to single-agent chemotherapy and may offer a more favorable toxicity profile.

T lymphocytes mediate immunologic control of C3 gene expression.

Immunologic control of C3 gene expression by tissue macrophages can be accomplished by treatment of spleen fragments with anti-C3 antibody. We now demonstrate that suppression of C3 requires participation of T lymphocytes of both the CD4+ and CD8+ phenotypes. Pretreatment of splenic tissue with anti-Thy-1.2 monoclonal antibody blocks the ability of the anti-C3 antibody to induce C3 suppression. Reduction in either the CD4+ or CD8+ subpopulations of T lymphocytes also abrogates C3 suppression demonstrating that both T cell subsets are required in addition to the inducing antibody. Artificially elevating intracellular levels of cAMP with cholera toxin can partially substitute for the effects mediated by T cells in this reaction. Therefore, normal expression of the C3 gene can be suppressed by a regulatory network that requires the presence of a specific inducing antibody and T lymphocytes of both the CD4+ and CD8+ subsets. This regulatory network has many similarities to regulatory networks that have been well documented in suppression of specific murine immunoglobulin allotypes.

Immunologic control of C3 gene expression in tissue macrophages.

Antigenic suppression of individual complement components can be induced when newborn animals or cells in tissue culture are treated for a period of time with antibody directed against that component. The initial exposure to antibody induces a network involving regulatory lymphocytes and soluble factors. Antigenic suppression has been accomplished either in vivo or in vitro with all three members of the evolutionarily related family C3, C4, and C5. In this report we have demonstrated that antigenic suppression is mainly the result of posttranscriptional regulation. After antibody treatment is terminated, during a period in which C3 protein is undetectable by sensitive assays, C3 mRNA is often briefly increased, after which it is modestly reduced. Therefore, the major mechanisms mediating immunologic control of C3 synthesis and secretion are not directly related to steady-state levels of C3 mRNA. The initially increased levels of C3 mRNA prove that there is no simple direct quantitative relationship between C3 mRNA and C3 synthesis and secretion. The later decreases in C3 mRNA levels are not sufficient to explain the quantitatively greater decreases in C3 synthesis. Therefore, the rate determining step in immune regulation of C3 production occurs after transcription. Regulation could be mediated by altered stability of C3 mRNA in the presence of antibody, formation of a defective primary transcript, defective processing of the transcript resulting in an abnormal mRNA, or a defective C3 translational apparatus. Although regulation is multifactorial, interference with translation is most likely to predominate.