Sympathetic neural responses to coronary occlusion during balloon angioplasty

OBJECTIVE: The sympathetic nervous system is a key modulator of prognosis and outcome in cardiac ischaemia and infarction. The effects of acute cardiac ischaemia on sympathetic neural traffic in humans are unknown. We tested the hypothesis that angioplasty, and associated transient myocardial ischaemia, elicits changes in neural circulatory control, including direct intraneural measures of sympathetic traffic. METHODS: We measured muscle sympathetic nerve activity (MSNA), blood pressure and heart rate in 12 patients (11 men, one woman) undergoing clinically indicated elective coronary angioplasty of the left anterior descending (n = 7) or circumflex (n = 5) coronary artery. Baseline data were obtained for 2 min before occlusion. Each balloon inflation was designed to last up to 120 s. RESULTS: Coronary occlusion had no significant effect on blood pressure or heart rate. In contrast, occlusion resulted in a significant increase in MSNA, in 10 of the 12 patients, and in all seven of those patients undergoing angioplasty of the left anterior descending artery. The group mean increase in MSNA during occlusion was 36 +/- 11% (P = 0.008 versus preocclusion). MSNA increased within 60 s of occlusion (129 +/- 12% of baseline; n = 12; P = 0.04), and increased further during the next 60 s to 141 +/- 12% of baseline levels (n = 10; P < 0.001). Increases in MSNA were similar in patients with and without significant chest pain (39 +/- 9% versus 34 +/- 13%, respectively; P = 0.84). CONCLUSION: Acute coronary occlusion during angioplasty increases central sympathetic outflow, but there is no systematic change in heart rate. The increase in sympathetic nerve traffic cannot be explained by blood pressure changes or occlusion-related chest pain.     

Differential proteomic profiling of mitochondria from Podospora anserina, rat and human reveals distinct patterns of age-related oxidative changes

According to the 'free radical theory of ageing', the generation and accumulation of reactive oxygen species are key events during ageing of biological systems. Mitochondria are a major source of ROS and prominent targets for ROS-induced damage. Whereas mitochondrial DNA and membranes were shown to be oxidatively modified with ageing, mitochondrial protein oxidation is not well understood. The purpose of this study was an unbiased investigation of age-related changes in mitochondrial proteins and the molecular pathways by which ROS-induced protein oxidation may disturb cellular homeostasis. In a differential comparison of mitochondrial proteins from young and senescent strains of the fungal ageing model Podospora anserina, from brains of young (5 months) vs. older rats (17 and 31 months), and human cells, with normal and chemically accelerated in vitro ageing, we found certain redundant posttranslationally modified isoforms of subunits of ATP synthase affected across all three species. These appear to represent general susceptible hot spot targets for oxidative chemical changes of proteins accumulating during ageing, and potentially initiating various age-related pathologies and processes. This type of modification is discussed using the example of SAM-dependent O-methyltransferase from P. anserina (PaMTH1), which surprisingly was found to be enriched in mitochondrial preparations of senescent cultures.     

Interleukin-18 as a mediator of systemic juvenile idiopathic arthritis

The objective of this report is to explore the balance between serum and synovial fluid levels of interleukin (IL)-18 in children with juvenile idiopathic arthritis (JIA). Blood samples were obtained from 81 children with JIA and 18 control children. Synovial fluid samples were collected from 16 children with oligoarticular JIA. Concentrations of IL-18 were determined using commercial kit. Patients with systemic JIA had higher serum levels of IL-18 than patients with other forms of JIA or control children, both during the active (median, range: 6,240, 1,600–78,750 pg/ml) and inactive (1,615, 513–3,270 pg/ml) phase of disease [analysis of variance (ANOVA), P < 0.05). Levels of IL-18 in sera of children with oligoarticular JIA (255, 89–4,342 pg/ml) were similar to the respective synovial fluid levels (217, 89–1,245 pg/ml). Serum levels of IL-18 were proportional to the erythrocyte sedimentation rate and levels of C-reactive protein, but inversely proportional to the haemoglobin levels. IL-18 appears to be an important mediator of systemic JIA, while it seems of a lesser relevance in pathogenesis of other JIA forms. Therefore, inhibition of IL-18 might be a base for a successful biological therapy for systemic JIA.     

Primary cardiac lymphoma presenting as atrial flutter and total heart block

Primary cardiac lymphoma is extremely rare. We present the case of a 70-year-old man with primary cardiac lymphoma involving interatrial septum, presenting as atrial flutter and total heart block. The diagnosis was obtained by echocardiography-guided transvenous endocardial biopsy which revealed diffuse large B-cell non-Hodgkin's lymphoma, CD 20+. After six courses of immunochemotherapy the patient achieved complete remission. After 2 months he developed a series of epileptic attacks. Intracerebral lymphoma extension was diagnosed. Two cycles of high-dose methotrexate and cranial irradiation were applied, resulting in a second complete remission.     

Reticulocyte haemoglobin content vs. soluble transferrin receptor and ferritin index in iron deficiency anaemia accompanied with inflammation

Ferritin concentration, as a parameter of iron status that is commonly used in the diagnosis of iron deficiency anaemia (IDA), often has limited values if the iron deficiency is accompanied by inflammatory disease. This study evaluated the value of reticulocyte haemoglobin content (CHr) and soluble transferrin receptor-ferritin index (sTfR/F) in the diagnosis of IDA and differential diagnosis of IDA and anaemia of chronic disease. The study included 66 nonanaemic individuals as controls, 86 patients with IDA divided into noninflammatory and inflammatory subgroups, and 32 patients with anaemia of chronic disease. Blood count, iron, transferrin saturation, total iron binding capacity, ferritin, C-reactive protein, sTfR and CHr were determined. Receiver operator characteristic curve analysis showed very high discriminating power for CHr, soluble transferrin receptor (sTfR) and sTfR/F in the diagnosis of IDA. In patients with anaemia of chronic disease these parameters showed no significant difference from the control. CHr and sTfR enabled recognition of iron deficiency and were not affected by acute phase reaction. They are sensitive markers of body iron status with additional value to conventional tests for the detection of iron deficiency.     

Clinical care of patients with amyotrophic lateral sclerosis

Although amyotrophic lateral sclerosis and its variants are readily recognised by neurologists, about 10% of patients are misdiagnosed, and delays in diagnosis are common. Prompt diagnosis, sensitive communication of the diagnosis, the involvement of the patient and their family, and a positive care plan are prerequisites for good clinical management. A multidisciplinary, palliative approach can prolong survival and maintain quality of life. Treatment with riluzole improves survival but has a marginal effect on the rate of functional deterioration, whereas non-invasive ventilation prolongs survival and improves or maintains quality of life. In this Review, we discuss the diagnosis, management, and how to cope with impaired function and end of life on the basis of our experience, the opinions of experts, existing guidelines, and clinical trials. We highlight the need for research on the effectiveness of gastrostomy, access to non-invasive ventilation and palliative care, communication between the care team, the patient and his or her family, and recognition of the clinical and social effects of cognitive impairment. We recommend that the plethora of evidence-based guidelines should be compiled into an internationally agreed guideline of best practice.