Evaluation of accessory cell heterogeneity. I. Differential accessory cell requirement for T helper cell activation and for T-B cooperation

Several Ia+ tumor cell lines and peritoneal exudate macrophages were tested as accessory cells (AC) for the activation of antigen-specific T cells and for T-B cooperation. The macrophages and all the Ia+ tumor lines tested induced the release of lymphokines from T cells in a major histocompatibility complex (MHC)-restricted fashion and reconstituted the antibody responses of AC-depleted spleen cells or of purified T and B cells. However, only the normal macrophages but none of the tumor lines induced carrier-specific T helper (Th) cells which help B cells for specific antihapten antibody responses by linked recognition. For T-B cooperation accessory cells were also required, but in contrast to Th cell activation any type of Ia+ AC (e.g. macrophage or tumor line) was effective. Strong MHC-restriction between the lymphocytes and the AC was seen if antigen-pulsed AC were added into the AC-depleted T-B cooperation cultures. If the AC and antigen were concomitantly added to the AC-depleted T-B cultures, MHC-restriction was less obvious. Concanavalin A supernatant reconstituted the response of AC-depleted T-B cultures provided antigen-specific Th cells and the hapten-carrier conjugate were present. If, however, tumor line-activated T cells were added instead of macrophage-induced Th cells, no cooperation with B cells took place even in the presence of Con A supernatant. The results obtained demonstrate a differential AC requirement for the induction of Th cells depending on the differentiation stage of the Th cells.     

Are myocardial infarction and venous thromboembolism associated? Population-based case–control and cohort studies

Introduction

Because the association of myocardial infarction (MI) and venous thromboembolism (VTE) is uncertain, we tested MI as a VTE risk factor and VTE as a predictor of MI.

Materials and Methods

Using Rochester Epidemiology Project resources, we identified all Olmsted County, MN residents with objectively-diagnosed incident VTE over the 13-year period, 1988–2000 (n = 1311), one to two resident controls per VTE case (n = 1511), and all residents with incident MI over the 31-year period, 1979–2010. For VTE cases and controls, we reviewed their complete medical records in the community for VTE and MI risk factors. Using conditional logistic regression we tested MI as a potential VTE risk factor, both unadjusted and after adjusting for VTE risk factors. We also followed VTE cases and controls without prior MI forward in time for incident MI through 12/31/2010, and using Cox proportional hazards modeling, tested VTE as a predictor of MI, both unadjusted and after adjusting for MI risk factors.

Results

The number (%) of MI prior to VTE among cases and controls were 75 (5.7) and 51 (3.4), respectively, and the number (%) of MI after VTE among cases and controls were 58 (4.4) and 77 (5.1), respectively. In univariate analyses, MI was significantly associated with VTE but not after adjusting for VTE risk factors. In both univariate and multivariate analyses, VTE (overall or idiopathic) was not a predictor of MI.

Conclusions

MI is not an independent risk factor for VTE, and VTE is not a predictor of MI.     

Serum HBsAg quantification in treatment-naïve Indian patients with chronic hepatitis B

Background and Aims

There is paucity of Indian data regarding serum HBsAg levels (qHBsAg) in treatment-naïve chronic hepatitis B (CHB). This study was done to determine correlation of qHBsAg with hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels and its ability to independently categorize subgroups of CHB.

Methods

We studied 131 treatment-naive CHB patients and initially classified them based on HBeAg status. The HBeAg-positive group was further classified into immune tolerance (IT) and immune clearance (IC) phases based on serum alanine aminotransferase. HBeAg-negative patients were classified into low replicators (LR) and HBeAg-negative chronic hepatitis (ENH) based on DNA levels. HBsAg quantification was performed using the Architect chemiluminescence system.

Results

HBeAg-positive patients had higher DNA (7.89 vs. 2.69 log₁₀?IU/mL) and higher qHBsAg (4.60 vs. 3.85 log₁₀?IU/mL) compared to the HBeAg-negative group. Good correlation between qHBsAg and DNA was seen in HBeAg-positive (ρ?=?0.6, p?<?0.001) but not in HBeAg-negative CHB (ρ?=?0.2). A qHBsAg level greater than 4.39 log₁₀?IU/mL predicted HBeAg-positive state with 81 % sensitivity and 85 % specificity. However, among HBeAg-negative CHB, qHBsAg failed to discriminate between LR and ENH.

Conclusions

A single point estimation of qHBsAg in treatment-naïve patients could predict replicative HBeAg-positive CHB, but was not helpful in defining replicative status in the HBeAg-negative CHB.     

Long-Term Clinical Outcomes of Underdosed Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Atrial Flutter

BackgroundAlthough direct oral anticoagulants (DOACs) have been shown to be effective at reducing the risk of stroke in patients with atrial fibrillation/flutter (AF), they are sometimes underdosed off-label to mitigate their associated higher bleeding risk. We sought to evaluate frequency and clinical outcomes of inappropriate underdosing of DOACS in patients with AF.MethodsWe conducted a study of subjects with AF who had a clinical indication for stroke prophylaxis (with a congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 47 years, sex category [CHA₂DS₂-VASc] of 2 or greater) and were prescribed 1 of the 4 clinically approved DOACs (apixaban, rivaroxaban, dabigatran, or edoxaban). We compared all-cause mortality, composite of stroke and systemic embolism, composite of myocardial infarction (MI), acute coronary syndromes (ACS), and coronary revascularization, and major bleeding between patients appropriately dosed and inappropriately underdosed.ResultsA total of 8125 patients met inclusion criteria, with a mean follow up of 2.2 ± 2 years. Of those, 1724 patients (21.2%) were inappropriately dosed. After adjusting for baseline variables, there was no difference in all-cause mortality, risk of stroke or systemic embolism, International Society on Thrombosis and Haemostasis (ISTH) major bleeding, or composite of myocardial infarction, acute coronary syndromes, or coronary revascularization between patients appropriately dosed and inappropriately underdosed. In subgroup analysis, only apixaban demonstrated an increased incidence all-cause mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.03-1.49) with inappropriate underdosing. There was no difference in the remaining clinical outcomes noted on subgroup analysis.ConclusionUnderdosing of DOACs did not minimize risk of bleeding, systemic embolization or all-cause mortality in patients with AF. Inappropriate underdosing with apixaban in particular was associated with increased all-cause mortality.     

Gene therapy in surgery

Summary Background With the increasing body of knowledge in molecular biology, gene transfer respectively gene therapy becomes more and more a valid therapeutic option. Methods This is a critical review of gene therapy protocols for treatment of different types of cancer. Furthermore, the pathophysiological mechanism, therapeutically strategies as well as experimental approaches toward gene transfer in septic shock and organ transplantation are critically elucidated. Results Gene transfer as a therapeutic option was first successfully applied in children with severe combined immunodeficiency (SCID) in 1990. The majority of gene marking or gene therapy protocols approved for human clinical trials to date are related to the treatment of cancer. Besides viral vectors for brain tumors, non-viral vectors, liposomes particularly, with almost no side effects are increasingly used. Conclusions Different approaches of gene transfer in cancer patients are under investigation. Experimental data of septic shock treatment and rejection therapy of the allograft in organ recipients with gene transfer are encouraging for future applications in clinical trials. Part II: “Application to septic shock and to organ transplantation” will be published in Acta Chir Austriaca 1997; 29: Issue 1. References are listed at the end of part. II.     

Performance characteristics and comparison of Abbott and artus real-time systems for hepatitis B virus DNA quantification

Virological monitoring of hepatitis B virus (HBV) DNA is critical to the management of HBV infection. With several HBV DNA quantification assays available, it is important to use the most efficient testing system for virological monitoring. In this study, we evaluated the performance characteristics and comparability of three HBV DNA quantification systems: Abbott HBV real-time PCR (Abbott PCR), artus HBV real-time PCR with QIAamp DNA blood kit purification (artus-DB), and artus HBV real-time PCR with the QIAamp DSP virus kit purification (artus-DSP). The lower limits of detection of these systems were established against the WHO international standards for HBV DNA and were found to be 1.43, 82, and 9 IU/ml, respectively. The intra-assay and interassay coefficients of variation of plasma samples (1 to 6 log(10) IU/ml) ranged between 0.05 to 8.34% and 0.16 to 3.48% for the Abbott PCR, 1.53 to 26.85% and 0.50 to 12.89% for artus-DB, and 0.29 to 7.42% and 0.94 to 3.01% for artus-DSP, respectively. Ninety HBV clinical samples were used for comparison of assays, and paired quantitative results showed strong correlation by linear regression analysis (artus-DB with Abbott PCR, r = 0.95; Abbott PCR with artus-DSP, r = 0.97; and artus-DSP with artus-DB, r = 0.94). Bland-Altman analysis showed a good level of agreement for Abbott PCR and artus-DSP, with a mean difference of 0.10 log(10) IU/ml and limits of agreement of -0.91 to 1.11 log(10) IU/ml. No genotype-specific bias was seen in all three systems for HBV genotypes A, C, and D, which are predominant in this region. This finding illustrates that the Abbott real-time HBV and artus-DSP systems show more comparable performance than the artus-DB system, meeting the current guidelines for assays to be used in the management of hepatitis B.     

Long-term experience with implanted intrathecal drug administration systems for failed back syndrome and chronic mechanical low back pain

Background  

Continuous intrathecal drug delivery has been shown in open studies to improve pain and quality of life in those with intractable back pain who have had spinal surgery. There is limited data on long term effects and and even less for patients with mechanical back pain without prior spinal surgery.     

MHC-restricted presentation of a single repeat of MUC1 mucin

Major histocompatibility complex (MHC) restriction of antigen presentation of a single mucin1 (MUC1) variable number of tandem repeats peptide (VNTR1) was examined by generating cytotoxic T lymphocytes (CTL) derived from peripheral blood mononuclear cells (PBMC) stimulated with a single repeat MUC1 peptide presented by allogeneic (MHC-independent) or autologous (MHC-dependent) Epstein-Barr Virus (EBV) immortalized B lymphocytes. The ability to generate greater CTL activity against MUC1-expressing tumor cells by stimulation with autologous versus allogeneic EBV-B supports the hypothesis that presentation of a single repeat of MUC1 peptide is MHC-restricted (MHC-dependent).     

Understanding health systems, health economies and globalization: the need for social science perspectives

ABSTRACT: The complex relationship between globalization and health calls for research from many disciplinary and methodological perspectives. This editorial gives an overview of the content trajectory of the interdisciplinary journal 'Globalization and Health' over the first six years of production, 2005 to 2010. The findings show that bio-medical and population health perspectives have been dominant but that social science perspectives have become more evident in recent years. The types of paper published have also changed, with a growing proportion of empirical studies. A special issue on 'Health systems, health economies and globalization: social science perspectives' is introduced, a collection of contributions written from the vantage points of economics, political science, psychology, sociology, business studies, social policy and research policy. The papers concern a range of issues pertaining to the globalisation of healthcare markets and governance and regulation issues. They highlight the important contribution that can be made by the social sciences to this field, and also the practical and methodological challenges implicit in the study of globalization and health.     

The use of bioabsorbable staple line reinforcement for circular stapler (BSG "Seamguard") in colorectal surgery: initial experience

Of all the complications associated with colorectal surgery, the most devastating and constant, despite all techniques being performed properly is anastomotic leakage, especially in left colon and rectal resections with rates as high as 50% when the rectum is involved. In 2005, our center published the preliminary experience with the use of linear staple line reinforcement for colon surgery. The purpose of this paper is to present a series of cases using a new conformation of bioabsorbable reinforcement for circular staplers in 5 patients, 2 patients with rectal cancer, 2 patients with diverticular disease, and 1 patient with sigmoid cancer. These initial data are very promising and has encouraged us to continue using this device on further patients.