Antiplatelet therapies in diabetes

Cardiovascular complications remain the main cause of mortality and morbidity in diabetes. This is related to advanced vascular pathology in this population, together with an enhanced thrombotic environment. The increased risk in thrombosis is secondary to platelet hyper-reactivity and increased levels and/or altered activity of coagulation factors. The current review is focused on the role of antiplatelet agents in modulating the thrombotic milieu in diabetes and improving vascular outcome in this high-risk population. We review the latest evidence for the use of aspirin in primary vascular prevention together with long-term treatment with this agent for secondary prevention. We also discuss the effects of the various P2Y₁₂ inhibitors, including clopidogrel, prasugrel and ticagrelor, on both short- and long-term secondary vascular prevention. Moreover, we briefly review antiplatelet therapies in special groups of people including those intolerant to aspirin, individuals with peripheral vascular disease and those with cerebrovascular pathology. The overall aim of this review is to provide the healthcare professional with a pragmatic guide for the management of thrombotic risk using established antiplatelet therapies to improve vascular outcome in persons with diabetes.     

Short-term high-dose folic acid does not alter markers of endothelial cell damage in patients with coronary heart disease

BACKGROUND AND OBJECTIVE: Endothelial dysfunction is an early, pre-clinical manifestation of coronary heart disease and is associated with increased plasma levels of von Willebrand factor (vWF), soluble E-selectin, and thrombomodulin, markers of endothelial cell damage/activation and reduced nitric oxide bioavailability. Homocysteine is associated with an increased risk of cardiovascular disease and mortality. High-dose folic acid treatment lowers plasma homocysteine by 25% and improves nitric oxide bioavailability; however, the effects on other indices of endothelial cell activation/damage has not been examined in patients with coronary heart disease and normal renal function. DESIGN AND METHODS: In a randomised, double-blind, cross-over study in 50 patients with coronary heart disease and normal serum creatinine, folic acid (5 mg/daily) was administered for 6 weeks and blood was analysed for von Willebrand factor, soluble E-selectin, and thrombomodulin. Endothelial nitric oxide bioavailability was assessed by flow-mediated dilatation. RESULTS: Plasma folate levels increased (9.1+/-3.4 vs. 310+/-235 microg/l; p<0.001) and nitric oxide bioavailability improved (47+/-35 vs. 110+/-43 microm; p<0.001) following active treatment. However, markers of endothelial cell injury were not significantly influenced (von Willebrand factor 118+/-33 vs. 119+/-34%; E-selectin 52+/-17 vs. 51+/-16 microg/l; thrombomodulin 3.94+/-1.81 vs. 3.94+/-1.51 microg/l; p=NS comparing post-placebo with post-folate). No correlation was observed between improvement in flow-mediated dilatation and change in endothelial marker proteins. INTERPRETATION AND CONCLUSION: These data suggest that endothelial markers are not useful surrogates of endothelial nitric oxide bioavailability in coronary heart disease and may be a less sensitive marker of endothelial function than nitric oxide.     

Specialty training in child and adolescent psychiatry in India

European Child & Adolescent Psychiatry - India has a considerable skilled manpower deficit in the area of child and adolescent mental health, given its population and their needs. To address...     

DA-EPOCH-R in Aggressive CD 20 Positive B Cell Lymphomas: Real-World Experience

Recent reports have shown that excellent survival outcomes can be achieved in adult Burkitt’s lymphoma with the use of DA-EPOCH-R regimen. When compared to earlier intense pediatric-type protocols, this regimen is less toxic. There are limited reports available on the use of this regimen outside the context of clinical trials. We analyzed the outcomes of patients who were treated with the DA-EPOCH-R regimen [Burkitt’s lymphoma (BL), primary mediastinal B cell lymphoma (PMBCL) and HIV-positive patients with diffuse large B cell lymphoma (DLBCL)] at our center over a 3 year period. Baseline characters, responses, and toxicity data was captured from records. Event-free survival (EFS—from therapy initiation till occurrence of event (non-achievement of complete response or relapse) and overall survival (OS—from therapy initiation till death due to any cause) were estimated using Kaplan–Meier method. Among 41 patients [median age 40 years (18–76)], the following diagnoses were included-HIV negative patients (N = 29): BL (N = 24), PMBCL (N = 5); HIV positive patients (N = 12): BL (N = 8), and DLBCL (N = 4). Among those with BL, majority had stage III/IV disease (N = 21/32, 65%). At the completion of planned therapy, 33 had achieved CR (81%). One patient died due to toxicity. The actuarial EFS and OS at 2 years were 80 and 77% respectively for all patients. The OS at 2 years was 100% for PMBCL, 80% for BL and 50% for HIV-positive DLBCL. Majority of the failures in BL were in patients with advanced disease. DA-EPOCH-R can be used in real-world setting and allows treatment of older patients with BL.     

Delayed activation of quiescent donor hematopoietic stem cells in the host marrow cavity by anti-host monoclonal antibody

To understand the mechanisms controlling hematopoietic engraftment in untreated, normal recipients, we investigated the fate of parental, donor hematopoietic stem cells after apparent graft failures in unconditioned F1 hybrid recipient mice. By administering an anti-host H- 2K monoclonal antibody, which targets host cells but spares the donor, we found that chimerism could be induced by delayed conditioning in animals with apparent graft failure. Engraftment kinetics in the host were followed by typing individual colony forming unit-- granulocyte/macrophage (CFU-GM) colonies for their origin and showed that parental cells, which were otherwise virtually absent, become promptly detectable within the marrow cavity after antibody administration. Marrow transfers to secondary hosts suggested that parental stem cells were present in the marrow of the untreated recipients. These findings establish that the elimination of all parental cells cannot account for the absence of peripheral blood chimerism in the unconditioned F1 hybrid recipient. Thus, viable and functional donor stem cells, which remain quiescent in the host marrow, can be activated by a selective conditioning regimen and can rescue an apparent graft failure. The selective activation in vivo of marked stem cells in an unirradiated microenvironment may be a useful system to study the regulation of cellular proliferation within the marrow cavity.     

Lung tumor-associated derepressed alloantigen coded for by the K region of the H-2 major histocompatibility complex

Transplacental induction of lung tumors in C3HfeB/HeN (C3Hf) strain mice can be readily achieved with the carcinogen 1-ethyl-1-nitrosourea. Several of these tumors express, as a tumor-associated transplantation antigen (TATA), a normal tissue alloantigen present in strain A and C3H/HeN (C3H) mice. In the present study it was shown that the tumor-associated alloantigen on the C3Hf-derived lung tumor 85 was present in all mice of H-2(a) and H-2(k) haplotypes tested and in CBA (532) strain mice (H-2(ka) haplotype). Studies using congenic-resistant and recombinant strains of mice indicated that the genetic locus controlling the expression of this antigen was either within or to the left of the H-2K region of the major histocompatibility complex (MHC). Thus the antigen was expressed in B10.A (4R) mice (kkbbbb MHC haplotype) but not in B10 (bbbbbb) or B10.AQR mice (qkkddd). The antigen was expressed in all tissues tested of C3H and A strain mice. It was not detected on any tissue tested including embryo tissue of C3Hf mice or mice of MHC haplotype other than H-2(k) or H-2(a). Because C3Hf strain mice were originally derived from C3H strain mice (H-2(k)), the MHC haplotype of C3Hf mice has been provisionally designated H-2(kb). The finding of a tumor-associated change in the expression of a H-2K region-coded antigen is consistent with the concept that MHC-coded antigens may act as targets for immunological surveillance of tumors.     

Circannual variation in lymphocyte subsets, revisited

BACKGROUND: Circadian and circannual variations in lymphocyte subsets, especially CD8+ T-lymphocytes, have been reported. This study focuses on CD4+ T-lymphocyte seasonal variation over a 6-year 8-month period. STUDY DESIGN AND METHODS: Lymphocyte subsets were quantitated monthly for four healthy individuals from 1986 through 1992 as part of a flow cytometry quality-control program. RESULTS: In general, there were no significant seasonal changes in the total number of white cells or in total lymphocyte counts. The absolute numbers of CD4+ T-lymphocytes were lowest in summer when the CD8+ T-lymphocytes were highest. Mean CD4+ T-lymphocyte counts were 846, 967, 618, and 695 per microL for Subjects 1 through 4, respectively, in winter and 432, 670, 355, and 766 per microL, respectively, in summer. Two healthy subjects had CD4+ T-lymphocyte counts lower than 300 per microL on one or more occasions during the study period. In three of the four subjects, the percentage of B-lymphocytes in winter was almost double that in summer. In one of the four subjects, no circannual rhythm was observed in these lymphocyte subpopulations. CONCLUSION: The seasonal variation in CD4+ T- lymphocyte counts demonstrated in three healthy individuals over almost 7 years is again of interest in light of renewed consideration of using surrogate tests, such as CD4+ T-lymphocyte counts, to screen for AIDS- like diseases that may be in the blood supply.     

Evaluation of antimotility effect of <Emphasis Type="Italic">Lantana camara L.</Emphasis> var. acuelata constituents on neostigmine induced gastrointestinal transit in mice

Background  

Lantana camara L. (Verbenaceae), a widely growing shrub which is toxic to some animal species, has been used in the traditional medicine for treating many ailments. The purpose of the present study was to evaluate the antimotility effects of Lantana camara leaf constituents in mice intestine.     

Prevalence, risk factors and virological profile of chronic hepatitis B virus infection in pregnant women in India

A large program was conducted by the Government of India to study the prevalence and profile of chronic hepatitis B virus (HBV) infection and its risk factors in pregnant women attending a tertiary care hospital in India. From September 2004 to December 2008 consecutive pregnant women attending the antenatal clinic were screened and those found positive for HBsAg were enrolled. Healthy non‐pregnant women of child‐bearing age, who presented for blood donation during the same period, served as controls. Women with symptoms of liver disease or those aware of their HBsAg status were excluded. Of the 20,104 pregnant women screened, 224 (1.1%) and of the 658 controls, 8 (1.2%) were HBsAg positive (P = ns). Previous blood transfusions and surgery were significant risk factors for infection with HBV. Of the women who were HBsAg positive, the ALT levels were normal in 54% of the women and HBV DNA levels were above 2,000 IU/ml in 71% of women. The median HBV DNA levels were higher in women who were HBeAg positive compared to the HBeAg negative group. The most common HBV genotype was D (84%) followed by A + D and A (8% each). In conclusion, the prevalence of HBsAg positivity among asymptomatic pregnant women in North India is 1.1% with 71% having high HBV DNA levels. These women may have a high risk of transmitting infection to their newborns. J. Med. Virol. 83:962–967, 2011. © 2011 Wiley‐Liss, Inc.     

3‐year follow‐up of 100 consecutive coronary bifurcation lesions treated with Taxus stents and the crush technique

Objectives : To determine the 3 year safety and efficacy of crush‐stenting with paclitaxel‐eluting stents. Background : The optimum two‐stent strategy for treatment of coronary bifurcation lesions is undetermined. Crush‐stenting is advocated to minimize restenosis through complete circumferential stent coverage; long‐term follow‐up data are lacking. Methods and Results : In a single center prospective registry, 100 consecutive patients with bifurcation lesions were treated with the Crush technique. The vast majority (93%) were true bifurcations, predominantly involving the left anterior descending and diagonal arteries. Technical success was 98%. Final kissing balloon dilatation, which became standard practice during the study, was attempted in 68 patients and successful in 51. Abciximab was used in all cases. There were no peri‐procedural stent thromboses. Follow‐up was 100% at 3 years. Symptom‐driven target lesion revascularisation was 8% at 3 years. Cumulative 3‐year major adverse cardiac events was 28% (7 cardiac deaths, 15 myocardial infarctions, 11 target vessel revascularisations). Absence of a final kissing inflation predicted repeat revascularisation but not death, infarction or stent thrombosis. Three probable stent thromboses occurred, of which two were very late. Conclusion : Where a two‐stent bifurcation strategy is required, Crush‐stenting with paclitaxel‐eluting stents is safe and effective in the long‐term. Failure to perform a final kissing dilatation increases the likelihood of revascularisation but not other adverse events. © 2009 Wiley‐Liss, Inc.