Outcomes of coronary artery bypass grafting versus percutaneous coronary intervention and medical therapy for multivessel disease with and without left ventricular dysfunction

Multiple randomized trials support the treatment of patients with multivessel coronary artery disease (CAD) and relatively normal left ventricular (LV) ejection fraction (EF) by either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). However, there has been a paucity of trials in the recent literature that have compared the outcomes of patients with multivessel CAD and low EF who undergo PCI or CABG. This review examines some of the clinical trials and series in this subgroup of patients and also compares the outcome of patients undergoing either procedure in the absence and presence of LV dysfunction. These trials and series support the notion that PCI can be successfully performed in patients with low EF with relatively low mortality, but that CABG is associated with greater freedom from repeat revascularization and from angina or congestive heart failure symptoms. In addition, most of the data published thus far indicate a long-term survival advantage among patients with ventricular dysfunction who have undergone CABG. Further studies, including randomized trials incorporating the evolving techniques of CABG and the recent advances in PCI, will be needed to assess the proper role and outcome of these two interventions.     

Hyperbaric oxygen therapy improves angiogenesis and bone formation in critical sized diaphyseal defects

Besides the use of autologous bone grafting several osteoconductive and osteoinductive methods have been reported to improve bone healing. However, persistent non‐union occurs in a considerable number of cases and compromised angiogenesis is suspected to impede bone regeneration. Hyperbaric oxygen therapy (HBO) improves angiogenesis. This study evaluates the effects of HBO on bone defects treated with autologous bone grafting in a bone defect model in rabbits. Twenty‐four New‐Zealand White Rabbits were subjected to a unilateral critical sized diaphyseal radius bone defect and treated with autologous cancellous bone transplantation. The study groups were exposed to an additional HBO treatment regimen. Bone regeneration was evaluated radiologically and histologically at 3 and 6 weeks, angiogenesis was assessed by immunohistochemistry at three and six weeks. The additional administration of HBO resulted in a significantly increased new bone formation and angiogenesis compared to the sole treatment with autologous bone grafting. These results were apparent after three and six weeks of treatment. The addition of HBO therapy to autologous bone grafts leads to significantly improved bone regeneration. The increase in angiogenesis observed could play a crucial role for the results observed. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:513–520, 2015.     

Proline at the P2 position in protein C is important for calcium- mediated regulation of protein C activation and secretion

Protein C is a vitamin K-dependent plasma serine protease zymogen, which upon activation, functions as an anticoagulant. Protein C activation is catalyzed by a complex of thrombin (T) with thrombomodulin (TM). This activation is Ca(2+)-dependent, but Ca2+ inhibits protein C activation by thrombin alone. In most proteases, specificity is determined primarily by the residues that lie near the scissile bond. In protein C, the P2 position is Pro, whereas in the fibrinogen A chain, P2 is Val. We have expressed a Pro-->Val mutant of protein C (P168V) in mammalian cells. At saturating Ca2+, the P168V and wild-type proteins were activated by the T-TM complex equivalently, but half maximal rates of activation were obtained at 50 mumol/L Ca2+ for wild type and approximately 5 mmol/L Ca2+ for the P168V mutant. In the absence of TM, Ca2+ no longer inhibited the activation of the P168V mutant. These results indicate that Pro168 influences the Ca(2+)- dependent conformational changes in protein C that control activation. Recently, a patient with thrombotic complications has been identified with a Pro168-->Leu substitution. Both the P168V and the P168L mutation lead to impaired secretion caused by retention within the cell.     

Existence of a pool of T-lymphocyte colony-forming cells (T-CFC) in human bone marrow and their place in the differentiation of the T- lymphocyte lineage

The existence and characteristics of bone marrow T-cell progenitors have not yet been established in man. Several pieces of evidence such as the reconstitution of certain immunodeficiencies by bone marrow graft suggest that T-cell precursors are present in the bone marrow. We report the growth of T-cell colonies from bone marrow populations using PHA-stimulated lymphocyte-conditioned medium containing T-cell growth factor (TCGF). Rosetting experiments and complement-dependent cytotoxicity assays with monoclonal antibodies indicate that the bone marrow T colony-forming cells (T-CFC) are E- OKT 3- and la+, i.e., immature progenitors. The colonies derived from these cells have the phenotype of mature T cells: E + OKT 3 + la- with either helper (OKT 4+) and suppressor (OKT 8 +) antigens. These results suggest that a thymic microenvironment may not be necessary for the in vitro proliferation and differentiation of the T-cell lineage in adult humans. These methodologies may permit direct investigation of early phenomena concerning the T-cell lineage, such as the acquisition of self-tolerance, the formation of a repertoire of specificities, and the HLA restriction phenomena that we believe takes place before the thymic maturation.     

Molecular therapy in gastroenterology and hepatology

During recent years, molecular techniques have significantly impacted our understanding and therapeutic concepts in gastrointestinal and liver disease. In a number of diseases, diagnostic work-up includes molecular data that supplements the phenotypical evaluation. This includes monogenic diseases as well as the identification of genetic risk factors (e. g. NOD2/CARD15 mutation in Crohn's disease) and viral disease. Attempts to replace liver transplantation in hereditary liver disease by targeted molecular interventions (e. g. via viral vectors) are still experimental, but the associated techniques have improved considerably. The molecular identification of therapeutic targets was followed by the development of specifically tailored therapeutics. These agents are mainly used in the treatment of chronic inflammatory bowel disease and gastrointestinal tumors.     

Isfahan Healthy Heart Programme: a comprehensive integrated community-based programme for cardiovascular disease prevention and control. Design,methods and initial experience

The Isfahan Healthy Heart Programme (IHHP) is a five to six year comprehensive integrated community-based programme for cardiovascular diseases (CVD) prevention and control via reducing CVD risk factors and improvement of cardiovascular healthy behaviour in a target population. IHHP started late in 1999 and will be finished in 2005-2006. A primary survey was done to collect baseline data from interventional (Isfahan and Najaf-Abad) and reference (Arak) communities. In a two-stage sampling method, we randomly selected 5 to 10 percent of households from randomly selected clusters. Then individuals aged > or = 19 years were selected for the survey. This way, data from 12,600 individuals (6300 in interventional counties and 6300 in the reference county) was collected and stratified according to living area (urban vs. rural) and different age and sex groups. The samples underwent a 30-minute interview to complete validated questionnaires containing questions on demography, socioeconomic status, smoking behaviour, physical activity, nutritional habits and other behaviour regarding CVD. Blood pressure and body mass index (BMI) measurements were done and fasting blood samples were taken for two hours post load plasma glucose (2 hpp), serum (total, HDL and LDL) cholesterol and triglyceride levels. A twelve-lead electrocardiogram was recorded in all persons above 35 years of age. Community-wide surveillance of deaths, hospital discharges, myocardial infarction and stroke registry was carried out in the intervention and control areas. Four to five years of interventions based on different categories such as mass media, community partnerships, health system involvement and policy and legislation have started in the intervention area while Arak will be followed without intervention. Considering the results of the baseline surveys, (assessments needed, the objectives, existing resources and the possibility of national implementation) the interventions were planned. They were set based on specific target groups like school children, women, work-site, health personnel, high-risk persons, and community leaders were actively engaged as decision makers. A series of teams was arranged for planning and implementation of the intervention strategies. Monitoring will be done on small samples to assess the effect of different interventions in the intervention area. While four periodic surveys will be conducted on independent samples to assess health behaviours related to CVD risk factors in the intervention and reference areas, the original pre-intervention subjects aged more than 35 years will be followed in both areas to assess the individual effect of interventions and outcomes like sudden death, fatal and nonfatal MI and stroke. The whole baseline survey will be repeated on the original and an independent sample in both communities at the end of the study.     

Howell‐Jolly bodies on peripheral smear leading to the diagnosis of congenital hyposplenism in a patient with septic shock

We present a case of isolated congenital hyposplenism that was discovered after the peripheral smear revealed Howell‐Jolly bodies. This case serves as the basis for a review of hyposplenism for the general practitioner.     

Efficacy and safety of telaprevir (TVR) triple therapy in a ‘real‐life’ cohort of 102 patients with HCV genotype 1: interim analysis after 24 weeks of treatment

Since 2011, telaprevir (TVR)‐based triple therapy is the new treatment standard for hepatitis C genotype 1 virus infection. The aim of our retrospective interim analysis encompassing the first 24 weeks on TVR‐based triple therapy was to assess ‘real‐life’ antiviral efficacy and side effects in a large single‐centre cohort, both in comparison with the data obtained in large prospective clinical trials. In total, we treated 102 patients: 24 treatment‐naïve patients, 58 patients pretreated with PEG‐IFN/RBV (thereof: 28 with nonresponse, 25 with relapse, five unknown) and 20 patients who previously had received nonpegylated interferon. 74 of 102 patients were assigned with HCV genotype 1b; 34 of 102 patients were treated in the context of liver cirrhosis. 72 of 102 patients have reached treatment week 24 (mean treatment duration 31 weeks). In the ITT analysis, overall response rates were at: week 4: 66%; week 12: 85%; and week 24: 78%. So far, 24 patients discontinued treatment prematurely, of those, 10 patients were due to virological failure. Haematological side effects were frequent (40% anaemia), as were ‘flu‐like’ symptoms (94%), rash (65%) and pruritus (79%). According to our interim ITT analysis encompassing up to 24 weeks of TVR‐based triple therapy, our ‘real‐life’ antiviral effects are comparable to the results of large multicentric clinical trials. However, TVR‐based triple therapy exhibited a high frequency of side effects requiring multiple therapeutic interventions. Notably, in our ‘real‐life’ cohort, no lethal case was observed so far.