Apoptosis of peripheral CD4(+) T-lymphocytes in end-stage renal disease patients under hemodialysis and rhEPO therapies

End-stage renal disease (ESRD) under hemodialyses (HD) is related with a higher propensity to infections, essentially due to T-cell lymphopenia. We postulated that HD procedure affects CD4(+) T cells, especially by inducing apoptotic death and that recombinant human erythropoietin (rhEPO) therapy may also play an important role in the modulation of the immune system in these patients. T-cell phenotype and apoptosis of HD patients and healthy controls were evaluated by flow cytometry using anticoagulated whole-blood samples. In 12 HD patients, these parameters were also analyzed before and immediately after HD procedure. HD patients showed a decrease in total circulating CD3(+) lymphocytes, especially in CD4(+) T cells (0.747 ± 0.410 vs. 0.941 ± 0.216 × 10(9)/L, p < 0.05), which could be a consequence of the higher proportion of CD3(+) and CD4(+) lymphocytes in the latest stage of apoptosis (or death) and of the higher proportion of apoptotic CD4(+) T cells observed in the patients immediately after HD procedure (2.91 ± 0.780 vs. 3.90 ± 1.96, p < 0.05). A positive and statistically significant correlation between CD3(+) and CD4(+) lymphocytes in latest stage of apoptosis (or death) with HD time was found (CD3(+): r = 0.592, p < 0.01; CD4(+): r = 0.501, p < 0.01). We also found a negative and significant correlation between weekly rhEPO doses and the number of CD4(+) T cells (r = -0.358, p < 0.05). In conclusion, HD procedure still contributes to the development of T-cell lymphopenia, at least in part, by apoptosis induction. It was also shown that rhEPO therapy is associated with the CD4(+) T-cell decline, possibly by immune modulation, eliminating atypical cells and helping to restore the CD4(+) T-cell subset.     

[18F]Fluoride labelling of macromolecules in aqueous conditions: silicon and boroaryl‐based [18F]fluorine acceptors, [18F]FDG conjugation and Al18F chelation

[¹⁸F]Fluorination is usually carried out by nucleophilic substitution reactions entailing the use of stringent conditions. A number of novel techniques including silicon and boron‐based fluoride acceptor molecules, [¹⁸F]fluoro‐2‐deoxy‐ d ‐glucose and chelation of the Al¹⁸F complex have been employed recently to achieve [¹⁸F]radiolabelling of macromolecules. These approaches are reviewed herein. Copyright © 2012 John Wiley & Sons, Ltd.     

Real-world comorbidities and treatment patterns of patients with acromegaly in two large US health plan databases

Acromegaly is a rare, chronic, and debilitating disease that results from excessive growth hormone production. Clinically, this disease is associated with enlargement of soft tissue, excessive skeletal growth, and increased risk of cardiovascular disease. Acromegaly is often diagnosed late, when a wide range of comorbidities may already be present. First-line therapy for acromegaly is typically surgery; but a number of highly-specific pharmacological agents have recently enabled a more aggressive medical management of acromegaly. Since surgical cure of acromegaly is low for macroadenomas, medical control of active acromegaly is an important component of treatment. There are no published US data currently available regarding real-world rates of comorbidities and treatment patterns among patients with acromegaly. This retrospective study examined the comorbidities and treatment patterns of 949 health plan enrollees, who had acromegaly diagnosis and/or procedure codes in an administrative claims database from July 1, 2002 through June 30, 2010. Acromegaly was associated with high rates of hypertension and diabetes along with a number of other comorbidities. The incidence of comorbidities was highest among patients with acromegaly-related treatment, which may have resulted, in part, from inadequate disease management and/or poor disease control. Unexpectedly, 55 % of patients identified with acromegaly received no treatment for acromegaly (i.e., surgery, radiotherapy, and medication) and only 28 % received a medication treatment during the observation period. However, some patients may have received a curative surgery prior to the observation period, which may have reduced the use of other acromegaly-related treatments during the study period. Of those treated with medications, the most common first medications were octreotide, cabergoline, and bromocriptine. Given the high incidence of serious comorbidities associated with active acromegaly, earlier diagnosis and treatment, along with appropriate follow-up care, may potentially avoid the life-long consequences of uncontrolled disease.     

Redistributional consequences of early childhood intervention

Recently, early investment in the human capital of children from socially disadvantaged environments has attracted a great deal of attention. Programs of such early intervention, aimed at children’s health and well-being, are spreading considerably in the US and are currently being tested in several European countries. In a discrete version of the Mirrlees model with a parents’ and a children’s generation, we model the intra-generational and the inter-generational redistributional consequences of such intervention programs. It turns out that the parents’ generation loses whenever such intervention programs are implemented. Furthermore, the rich part of the children’s generation always benefits. Despite the expectation that early intervention puts the poor descendants in a better position, our analysis reveals that the poor among the children’s generation may even be worse off, if the effect of early intervention on their productivity is not large enough.