A NOTE ON THE FATE OF TARTRATES IN THE BODY

Under the experimental conditions outlined, sodium tartrate subcutaneously introduced into rabbits fails to reappear in the urine. It is concluded that the disintegrative influence of the salt upon the convoluted tubules is sufficient to account for the failure of the salt to be eliminated. No evidence of a vicarious function on the part of the glomerulus was observed.     

Tregs utilize β-galactoside-binding protein to transiently inhibit PI3K/p21 activity of human CD8 T cells to block their TCR-mediated ERK activity and proliferation

Regulatory T cells (Tregs) and beta-galactoside-binding protein (βGBP), a regulatory protein often found expressed at sites of immunological privilege, have similar functions. Their presence affects the outcome of harmful autoimmunity and cancers, including experimental autoimmune encephalomyelitis and malignant gliomas. Here we report a novel pathway by which Tregs express and utilize βGBP to control CD8⁺ T cell responses partially activating TCR signaling but blocking PI3K activity. As a result, this leads to a loss of p21^ras, ERK and Akt activities despite activation of TCR proximal signals, such as phosphorylation of CD3ζ, Zap70, Lat and PKCθ. Although non-processive TCR signaling often leads to cell anergy, Tregs/βGBP did not affect cell viability. Instead, βGBP/Tregs transiently prevented activation of CD8⁺ T cells with self-antigens, while keeping their responses to xenogeneic antigens unaffected.     

The MTA at 8 Years: Prospective Follow-up of Children Treated for Combined-Type ADHD in a Multisite Study

ObjectivesTo determine any long-term effects, 6 and 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA; N = 436); to test whether attention-deficit/hyperactivity disorder (ADHD) symptom trajectory through 3 years predicts outcome in subsequent years; and to examine functioning level of the MTA adolescents relative to their non-ADHD peers (local normative comparison group; N = 261).MethodMixed-effects regression models with planned contrasts at 6 and 8 years tested a wide range of symptom and impairment variables assessed by parent, teacher, and youth report.ResultsIn nearly every analysis, the originally randomized treatment groups did not differ significantly on repeated measures or newly analyzed variables (e.g., grades earned in school, arrests, psychiatric hospitalizations, other clinically relevant outcomes). Medication use decreased by 62% after the 14-month controlled trial, but adjusting for this did not change the results. ADHD symptom trajectory in the first 3 years predicted 55% of the outcomes. The MTA participants fared worse than the local normative comparison group on 91% of the variables tested.ConclusionsType or intensity of 14 months of treatment for ADHD in childhood (at age 7.0–9.9 years) does not predict functioning 6 to 8 years later. Rather, early ADHD symptom trajectory regardless of treatment type is prognostic. This finding implies that children with behavioral and sociodemographic advantage, with the best response to any treatment, will have the best long-term prognosis. As a group, however, despite initial symptom improvement during treatment that is largely maintained after treatment, children with combined-type ADHD exhibit significant impairment in adolescence. Innovative treatment approaches targeting specific areas of adolescent impairment are needed.     

Race as an Independent Risk Factor for Breast Cancer Survival: Breast Cancer Outcomes From the Medical College of Georgia Tumor Registry

BackgroundCauses of racial disparities in breast cancer survival remain unclear. This study assesses overall survival (OS) after diagnosis between black and white women and examines factors that might correlate with this disparity.Patients and MethodsData were obtained from the Medical College of Georgia Tumor Registry. Cases included those diagnosed between 1990 and 2005. We analyzed race, stage, age of diagnosis, and treatment received: chemotherapy, radiation, surgery, and hormonal therapy. A Cox proportional hazards model was used to determine differences in OS.ResultsCompared with 670 white women, 489 black women were more likely to be younger, have later-stage disease at diagnosis, and were less likely to have received hormonal therapy. Both groups received similar rates of radiation, surgery, and chemotherapy. Black women had significantly poorer OS (adjusted hazard ratio, 1.35; 95% CI, 1.12–1.63). White women had a 5-year OS of 54% compared with 45% in black women (P = .0031). Having received radiation, surgery, or chemotherapy was not associated with OS. White women were more likely to have received hormonal therapy, which had a significant protective effect. However, a stratified analysis (between those who received hormonal therapy and those who did not) showed similar results, whereas black women experienced poorer OS in both strata.ConclusionBlack women with breast cancer had a significantly poorer OS compared with white women. White women received more hormonal therapy, which had a protective effect. There were no differences in treatment received regarding radiation, surgery, or chemotherapy, and these treatments were not associated with OS. The reasons for racial disparities in breast cancer OS remain complex.     

Precocious expression of T cell functional response genes in vivo in primitive thymocytes before T lineage commitment

The genes encoding effector molecules of mature T cells, IL-2, perforin and IL-4, were found to be expressed in vivo in the most primitive subsets of thymocytes of adult mice. These subsets have previously been identified by their cell surface markers and by their expression of other T lineage-associated genes. While IL-2, perforin and IL-4 are expressed in distinct patterns, all three are expressed before the induction of RAG-1 and pre-TCR alpha mRNA expression, and are confined to subsets of cells that apparently have not yet undergone commitment to the T lineage. Thus, expression of T cell response genes appears to be one of the earliest markers of lymphocyte differentiation. Activation events marked by CD69 induction occur in these early cell types, but the response gene expression by these cells is separable from CD69 expression. IL-2 and perforin are induced again much later in thymocyte development, during TCR-dependent repertoire selection. At those stages, IL-2 protein and RNA levels per cell are higher, but the fraction of cells expressing IL-2 appears to be much lower than in the most immature stages. In addition, a striking feature of the immature populations is the robust IL-2 expression by presumptive immature NK cells. These findings are discussed in terms of the developmental origins of lineage specificity in T cell response gene regulation.      

Cost-effectiveness of low-molecular-weight heparin and unfractionated heparin in treatment of deep vein thrombosis

BACKGROUND: Acute deep vein thrombosis has traditionally been treated with unfractionated heparin (UFH), administered intravenously, but low-molecular-weight heparins (LMWH), administered subcutaneously, have recently become available. The authors sought to determine which therapy was more cost-effective for inpatient and outpatient treatment of deep vein thrombosis. METHODS: An incremental cost-effectiveness analysis based on a decision tree was performed for 4 treatment strategies for deep vein thrombosis. Rate of major hemorrhage while receiving heparin, rate of recurrence of venous thromboembolism 3 months after treatment and mortality rate 3 months after treatment were determined by meta-analysis. Costs for the UFH therapy were prospectively collected by a case-costing accounting system for 105 patients with deep vein thrombosis treated in fiscal year 1995/96. The costs for LMWH therapy were modelled, and cost-effectiveness was determined by decision analysis. RESULTS: Meta-analysis revealed a mean difference in risk of hemorrhage of -1.1% (95% confidence interval [CI] -2.4% to 0.3%), a mean difference in risk of recurrence of venous thromboembolism of -2.6% (95% CI -4.5% to -0.7%) and a mean difference in risk of death of -1.9% (95% CI -3.6% to -0.4%), all in favour of subcutaneous unmonitored administration of LMWH. The cost to treat one inpatient was $2993 for LMWH and $3048 for UFH. Even more would be saved if LMWH was delivered on an outpatient basis (cost of $1641 per patient). The cost-effectiveness analysis showed that LMWH in any treatment setting is more cost effective than UFH. A sensitivity analysis demonstrated the robustness of this conclusion. INTERPRETATION: Treatment of deep vein thrombosis with LMWH is more cost effective than treatment with UFH in both inpatient and outpatient settings.     

Outcome of mid-urethral sling procedures in Korean women with stress urinary incontinence according to body mass index

BACKGROUND: The objective of this study was to determine whether the outcome of mid-urethral sling procedures is influenced by the body mass index of Korean women suffering from stress urinary incontinence (SUI). METHODS: A total of 285 women, ranging in age from 28 to 80 years (mean 55.4), all of whom were followed up for at least 6 months, were ultimately included in this study. The patients were classified as follows: normal weight, 18.5-23 kg/m2; overweight, 23-27.5 kg/m2; obesity, 27.5 kg/m2 or higher. RESULTS: We noted bladder perforations in 11 cases (4.9%, 3.8% and 2.2% in the normal weight, overweight, and obesity groups, respectively; P = 0.449). We determined there to be no significant differences among the three groups with regard to cure rate (P = 0.173). The rates of postoperative urinary retention were 9.9% in the normal weight group, 10.1% in the overweight group, and 15.6% in the obesity group (P = 0.396). We determined there to be no significant differences among the three groups with regard to the persistence of urgency (P = 0.312). Seventy-nine patients (27.7%) exhibited symptoms indicative of voiding disorder (hesitancy, poor flow, or sensations of incomplete emptying). The postoperative development of these voiding symptoms was not significantly different among the three groups (P = 0.106). CONCLUSION: Our results demonstrate both the feasibility and the safety of mid-urethral sling procedures for obese Korean women who suffer from SUI. Additional studies, including prospective randomized trials with longer follow-up periods, will be required in order to confirm these findings.