[Vomiting and collapse of a 28-year-old male long distance runner in middle European Summer]. / Erbrechen und Kollaps bei einem 28-jährigen Langstreckenläufer im mitteleuropäischen Sommer.

BACKGROUND: Hyperthermia often ends fatally and must therefore be promptly recognized and adequately treated. CASE: A 28-year-old man participated in a long-distance race (3 km) on a hot summer day (28 °C). The runner collapsed, had to vomit but continued the run and reached the finish. Neurologically, the patient presented with intermittent cerebral seizures. External cooling batteries were immediately applied and cold infusions were started. The patient was admitted to the intensive care unit of the university hospital (body temperature 40.2 °C). After a few hours, a manifest disseminated intravascular coagulopathy developed with multiple organ failure. It took 12 l of volume replacement, 8 units of fresh frozen plasma and 2 units of erythrocyte concentrates in the first 12 h to stabilize the patient. Although with the help of forced external cooling and application of cold infusions, the body temperature could be lowered to 38 °C by the next morning, the overall situation of the patient continued to deteriorate. Despite dialysis and massive substitution of coagulation factors, the patient could not be sufficiently stabilized and died of brain edema. CONCLUSION: Not only the old or young children are subject to the potential danger of a fatal heat stroke but also young athletic persons after normal sports activities (3 km run). Cooling must be started immediately and the patient must be hospitalized as a vital emergency. If hemostasis fails due to the heat-related loss of hepatogenic protein synthesis, a viscious circle begins, which, as in the reported case, is irreversible despite maximum therapy and substitution.

[Recurrent pain and swelling of the left leg in a 49-year-old male patient]. / Rezidivierende Beinschwellungen und Schmerzen im linken Bein bei einem 49-jährigen Patienten.

A 49-year-old male patient presented due to recurrent pain and swelling in the left leg. The patient had had deep venous thrombosis with pulmonary embolism 5 years previously. Since then, he had been treated with Vit-k-antagonists. Pronounced paraumbilical collateral circulation of unknown origin was striking. Doppler sonographic evaluation pointed to May-Thurner syndrome. This was confirmed by phlebography. Venous stenting of the stenosis in the left iliac vein achieved long-term symptom improvement. This case report is intended to draw attention to the rare May-Thurner syndrome as an important differential diagnosis of deep vein thrombosis and, at the same time, identify diagnostic and therapeutic treatment strategies.

Role of exercise cardiogoniometry in coronary artery disease diagnostics.

BACKGROUND: The use of noninvasive diagnostics in coronary artery disease remains underdeveloped. To date, there is no simple and inexpensive method that can lead to a reliable diagnosis. Aside from costly and elaborate imaging techniques, exercise ECG, with its rather moderate sensitivity and specificity, is the main diagnostic method available. METHODS: In this prospective study of 109 patients, the diagnostic value of cardiogoniometry (CGM), a three-dimensional, computer-analyzed vector cardiogram, was determined before and after physical stress, and the results were compared with those obtained from a stress test. We also investigated whether the sensitivity and specificity of the classical bicycle stress test could be increased with the addition of measurements obtained by CGM. Coronary angiography was used as a reference method. RESULTS: CGM had a sensitivity of 39% at rest and 42% after physical stress and a specificity of 63% at rest and 57% after stress. This method was found to be markedly inferior to pre-test probability (sensitivity 53%, specificity 81%), stress ECG (sensitivity 52%, specificity 81%), and resting ECG (sensitivity 50%, specificity 64%). The efficiency of exercise ECG testing was not improved by use of CGM results. CONCLUSION: If CGM is to be established as a viable diagnostic method in daily clinical practice, it must undergo further development.

[Rendu-Osler-Weber disease : More than just a nosebleed]. / Morbus Osler : Mehr als nur Nasenbluten.

A 72-year-old female patient presented with increasing dyspnea of unclear origin classified as New York Heart Association stage III (NYHA III). Using transesophageal echocardiography a patent foramen ovale (PFO) and right heart failure could be diagnosed. Right heart catheterization revealed a large left to right shunt due to an arteriovenous malformation in the liver. Because of additional telangiectasia of the lips the presumptive diagnosis was Rendu-Osler-Weber disease. Typical nosebleeds and other symptoms of the disease were lacking and only two out of four Curaçao criteria were positive; therefore, genetic testing was performed, which verified the clinical diagnosis. Off-label use of the angiogenesis inhibitor bevacizumab was initiated as the therapeutic strategy and led to an improvement in the symptomatic dyspnea.

Vascular hippocampal plasticity after aerobic exercise in older adults.

Aerobic exercise in young adults can induce vascular plasticity in the hippocampus, a critical region for recall and recognition memory. In a mechanistic proof-of-concept intervention over 3 months, we investigated whether healthy older adults (60-77 years) also show such plasticity. Regional cerebral blood flow (rCBF) and volume (rCBV) were measured with gadolinium-based perfusion imaging (3 Tesla magnetic resonance image (MRI)). Hippocampal volumes were assessed by high-resolution 7 Tesla MRI. Fitness improvement correlated with changes in hippocampal perfusion and hippocampal head volume. Perfusion tended to increase in younger, but to decrease in older individuals. The changes in fitness, hippocampal perfusion and volume were positively related to changes in recognition memory and early recall for complex spatial objects. Path analyses indicated that fitness-related changes in complex object recognition were modulated by hippocampal perfusion. These findings indicate a preserved capacity of the aging human hippocampus for functionally relevant vascular plasticity, which decreases with progressing age.

Relation of impaired interorgan communication and parasympathetic activity in chronic heart failure and multiple-organ dysfunction syndrome.

BACKGROUND: We investigated the relationship of impaired autonomic function and severity of illness in chronic heart failure (CHF) and multiple-organ dysfunction syndrome (MODS) as an end stage of CHF. Furthermore, we assessed the link of parasympathetic modulation of the heart rate and inflammatory activation in CHF and MODS. METHODS: Sixty-five patients admitted for worsening of CHF were retrospectively enrolled in this study. In addition, 65 age- and sex-matched patients with pronounced MODS were assigned for comparison of autonomic function and C-reactive protein in patients with CHF or MODS, respectively. Heart rate variability (HRV) parameters of the time and frequency domain as markers of autonomic function were analyzed from 24-hour Holter electrocardiograms. RESULTS: The more pronounced the severity of illness as expressed by the Acute Physiology and Chronic Health Evaluation score, the more the HRV was impaired. This effect was particularly seen for overall variability (SD of RR intervals) and HRV parameters characterizing the parasympathetic modulations of the heart rate (high, very low frequency power). C-reactive protein levels as markers of inflammation were inversely related to high and very low frequencies. CONCLUSION: Our results allow for speculation that autonomic dysfunction in CHF indicates a beginning of uncoupled interorgan communication potentially leading to MODS as characterized by disruption of communication between the organs.

Isolation and intravenous injection of murine bone marrow derived monocytes.

As a subtype of leukocytes and progenitors of macrophages, monocytes are involved in many important processes of organisms and are often the subject of various fields in biomedical science. The method described below is a simple and effective way to isolate murine monocytes from heterogeneous bone marrow. Bone marrow from the femur and tibia of Balb/c mice is harvested by flushing with phosphate buffered saline (PBS). Cell suspension is supplemented with macrophage-colony stimulating factor (M-CSF) and cultured on ultra-low attachment surfaces to avoid adhesion-triggered differentiation of monocytes. The properties and differentiation of monocytes are characterized at various intervals. Fluorescence activated cell sorting (FACS), with markers like CD11b, CD115, and F4/80, is used for phenotyping. At the end of cultivation, the suspension consists of 45%± 12% monocytes. By removing adhesive macrophages, the purity can be raised up to 86%± 6%. After the isolation, monocytes can be utilized in various ways, and one of the most effective and common methods for in vivo delivery is intravenous tail vein injection. This technique of isolation and application is important for mouse model studies, especially in the fields of inflammation or immunology. Monocytes can also be used therapeutically in mouse disease models.

[The molecular bypass: an established method for revascularisation of non-operable PAD patients or merely a future vision]. / Der molekulare Bypass: eine etablierte Methode zur Revaskularisation von inoperablen pAVK-Patienten oder nur eine Zukunftsvision?

Collateral vessel growth is a physiological process that is not equally pronounced in all people. After the development of a haemodynamically relevant stenosis in vascular systems, blood flow is directed through a collateral circulation to supply ischaemic tissue. This collateral circulation exists on the capillary level and by definition, is not composed of real new vessels. Postnatal vasculogenesis (true neovascularisation) occurs in the adult organism in tumour vascularisation, wound healing, in the endometrium, and in the context of chronic diseases such as rheumatoid arthritis and psoriasis. Reopening of the occluded vessel or use of artificial bypass grafts are the most attractive therapeutic approaches for treating peripheral arterial and coronary artery disease. These strategies have been exhausted in many patients; therefore augmentation of arteriogenesis can be more useful. Arteriogenesis, the promotion of natural collateral growth, is a hot topic in vascular research. Monocytes play a key role in arteriogenesis by "homing" to areas of collateral vessel growth and locally secrete multiple essential growth factors. Furthermore, stem cells of different origins, endothelial progenitor cells or mononuclear cells are currently being used to promote vessel growth. Also, the application of growth factors such as VEGF, MCP-1, GM-CSF have been already used in clinical trials. This review article describes the physiology and pathophysiology of vascular stenoses and their compensation mechanisms. The review also gives an overview of current treatment approaches and new strategies for non-operable PAD patients. The article presents the current cell and growth factor-related studies, as well as results of balloon dilatation and stent implantation or bypass surgery studies for improvement of revascularisation.

[What the surgeon needs to know about basic new concepts of inflammation and their therapeutic consequences: sanitation of inflammation is not a passive but rather an active process regulated by lipid mediators]. / Was der Chirurg über grundlegend neue Konzepte zur Entzündung und deren therapeutische Konsequenzen wissen sollte: Die Ausheilung der Entzündung ist kein passiver, sondern ein durch Lipidmediatoren regulierter aktiver Prozess.

The acute inflammatory response as a physiological programme that protects the organism against injurious pathogens is characterised by highly regulated actions of pro- and anti-inflammatory mediators. Intensive investigations during the last decades have led to the identification of these mediators and their complex interplay as well as the design and development of anti-inflammatory therapies. However, the resolution of acute inflammation has long been considered to be a passive process. In consequence, little was known about the mechanisms which guide acute inflammation either to complete resolution, repair of inflamed tissue and restoration of normal function or to a chronic inflammatory process characterised by persistent signs of inflammation, tissue damage and impaired function. Predominantly during the last decade the so-called specialised proresolving mediators (SPM) have been identified. These essential fatty acid-derived mediators - lipoxins, resolvins, protectins, and maresins - terminate the acute inflammatory responses and stimulate their complete resolution. SPM possess both anti-inflammatory and proresolving activities in that they inhibit pro-inflammatory cytokines, limit infiltration of neutrophils, enhance macrophage uptake, and finally stimulate their non-phlogistic activation and clearance of apoptotic neutrophils and microbial particles. It has been demonstrated in multiple animal models of human inflammatory diseases that, e.g., atherosclerosis, diabetes, and inflammatory bowel diseases are caused by a decreased synthesis and/or an impaired signal transduction of the proresolving mediators. Future studies are warranted to clarify whether these proresolving lipid mediators will participate in healing human inflammatory diseases and their complications.

Treatment with aliskiren/amlodipine combination in patients with moderate-to-severe hypertension: a randomised, double-blind, active comparator trial.

AIMS: To assess the extent of reduction in blood pressure (BP) of aliskiren/amlodipine combination therapy compared with amlodipine monotherapy in moderate-to-severe hypertensive patients. METHODS: This was an 8-week multicentre, randomised, double-blind study. After a 1-to 4-week washout period, eligible patients [mean sitting systolic blood pressure (msSBP) ≥ 160 to < 200 mmHg] were randomised to receive a once-daily dose of aliskiren/amlodipine 150/5mg (n = 244) or amlodipine 5 mg (n = 241) for 1 week, followed by up-titration to aliskiren/amlodipine 300/10 mg or amlodipine 10 mg for 7 weeks. Efficacy outcome measures included change from baseline to week 8 endpoint in msSBP (primary endpoint), mean sitting diastolic blood pressure (msDBP), and BP control rate (< 140/90 mmHg). Safety was assessed by monitoring and recording all adverse events (AEs) and laboratory abnormalities. RESULTS: Patients' demographic characteristics were balanced between the two groups, mean baseline BP being 171.0/94.3 mmHg for aliskiren/amlodipine and 171.8/95.6 mmHg for amlodipine. Of 485 randomised patients, 433 (89.3%) completed the study. At week 8 endpoint, combination therapy resulted in significantly greater msSBP/msDBP reductions and BP control rate, compared with monotherapy (all: p ≤ 0.0001). The overall incidence of AEs was similar between the two groups. The most commonly reported AE was peripheral oedema with the incidence lower for combination therapy (14.4%) than for monotherapy (18.3%). CONCLUSION: In this population with considerably elevated BP, use of aliskiren/amlodipine combination showed significantly greater BP reductions and allowed more patients to achieve BP control compared with amlodipine monotherapy, with no additional safety concerns.

[19-year-old asthma patient with pronounced eosinophilia and acute coronary syndrome]. / 19-jähriger Asthmatiker mit ausgeprägter Eosinophilie und akutem Koronarsyndrom.

Diagnosis of Churg-Strauss syndrome should be considered in young asthmatics with fatigue and eosinophilia. On the base of the etiopathology of a 19-year old man, who was initially admitted because of dyspnoea, fever and acute chest pain, we show that eosinophilia gives an important hint for further diagnostic and is the key trend parameter. Histologically an eosinophilic myocarditis could be shown in the myocardial biopsy. High dose prednisolone induced a clear improvement in symptoms, with decrease of the inflammatory signs and the eosinophilia and a clear improvement of the left ventricular function.

Ultrasound guided thrombin injection of pseudoaneurysm of the radial artery after percutaneous coronary intervention.

Thrombin injection is frequently used to occlude iatrogenic pseudoaneurysms in larger vessels, but has never successfully been used in the radial artery location. Here we report the use of this treatment in a patient with radial artery pseudoaneurysm following coronary intervention. After Doppler sonographic visualization of the pseudoaneurysm cavity and its neck, an ultrasound-guided transcutaneous injection of thrombin was carried out. Immediately after the injection, the pseudoaneurysm was completely clotted and Doppler measurement confirmed the stop of blood flow. The result suggests that ultrasound-guided injection of thrombin into a radial artery pseudoaneurysm following coronary intervention is a feasible alternative to surgical intervention.

Deazaadenosine prevents leukozyte evasion during acute cardiac allograft rejection by suppression of adhesion molecule expression.

BACKGROUND: In the initial phase after cardiac transplantation, mononuclear cells infiltrate the graft initiating a relevant impulse for rejection. 3-Deazaadenosin (c3Ado), an analog of adenosine, has demonstrated in vitro anti-inflammatory properties. Furthermore, in vivo studies on arteriosclerosis development and septic myocardial dysfunction c3Ado revealed reduced cellular infiltration. In addition ischemia and reperfusion injury could be diminished in a pulmonary animal model. The aim of our study was to investigate the properties of c3Ado to reduce adhesion molecule expression and cellular infiltration in a fully allogeneic cardiac transplant model. METHODS AND RESULTS: Lewis rats were challenged with Wistar-Furth cardiac allografts. Untreated grafts were rejected within 7 days (group 1). In group 2, animals received 2 x 5 mg c3Ado SC per day. Grafts were harvested on days 1, 3, and 6 after transplantation for further examination (n = 4 per group and time point). Immunohistochemical examination revealed significant reduction of graft-infiltrating MHC II positive cells, T-cell receptor positive cells (R73), as well as ED1-positive monocytes and macrophages (P < .01) at days 3 and 6 after transplantation. Adhesion molecule (ICAM-1, VCAM-1) expression on days 1 and 3 after transplantation was almost completely diminished in c3Ado-treated grafts. CONCLUSION: Thus, c3Ado is able to reduce graft infiltration by preventing leukocyte evasion through the suppression of adhesion molecule expression. This may be a novel strategy to protect transplanted organs from early damage after transplantation and extend organ survival after transplantation.

Reversible clopidogrel resistance due to right ventricular myocardial infarction: risk factor of recurrent stent thrombosis?

A 63-year-old male Patient was admitted to the intensive care unit due to acute inferior myocardial infarction with right ventricular dysfunction. He received a loading dose of clopidogrel (600 mg) and aspirin (500 mg) and was immediately revascularized by reopening of the proximal right coronary artery (RCA) and implantation of a bare metal stent. After primary successful intervention the patient suffered from thoracic pain on day 5 of admission. The ECG indicated reinfarction. The proximal RCA was again re-opened by PTCA alone. The following day the patient suffered again from thoracic pain with ST-elevation in the inferior leads, this time complicated by additional total AV-blockade. The angiography showed another time a thrombotic occlusion of the initially implanted stent. He received another intervention with implantation of additional two bare-metal stents, an aortic counter-pulsation and a temporary two-chamber pace maker. Tirofiban was administered for 24 h and the IABP was withdrawn after 60 h. The patient was discharged on Aspirin 300 mg/d, Clopidogrel 150 mg/d and Enoxaparin 40 mg/d. Six weeks later the patient demonstrated an improved right ventricular function (TAPSE 18 mm), liver enzymes were normal, and inhibition of platelet aggregation by clopidogrel (150 mg/d) was sufficient. In conclusion this implies that the reversible "clopidogrel-resistance" might have been due to congestion and reduced metabolism due to right ventricular infarction.

Neurokinin-1 receptor activation induces reactive oxygen species and epithelial damage in allergic airway inflammation.

BACKGROUND: An induction of reactive oxygen species (ROS) is characteristic for inflammation but the exact pathways have not been identified for allergic airway diseases so far. OBJECTIVE: The aim of this study was to characterize the role of the tachykinin NK-1 receptor on ROS production during allergen challenge and subsequent inflammation and remodelling. METHODS: Precision-cut lung slices of ovalbumin (OVA)-sensitized mice were cultivated and ROS-generation in response to OVA challenge (10 microg/mL) was examined by the 2',7'-dichloroflourescein-diacetate method. Long-term ROS effects on epithelial proliferation were investigated by 5-bromo-2'-deoxyuridine incorporation (72 h). In vivo, the results were validated in OVA-sensitized animals which were treated intra-nasally with either placebo, the tachykinin neurokinin 1 (NK-1) receptor antagonist SR 140333 or the anti-oxidant N-acetylcystein (NAC) before allergen challenge. Inflammatory infiltration and remodelling were assessed 48 h after allergen challenge. RESULTS: ROS generation was increased by 3.7-fold, which was inhibited by SR 140333. [Sar(9),Met(11)(O(2))]-Substance P (5 nM) caused a tachykinin NK-1 receptor-dependent fourfold increase in ROS generation. Epithelial proliferation was decreased by 68% by incubation with [Sar(9),Met(11)(O(2))]-SP over 72 h. In-vivo, treatment with SR 140333 and NAC reduced epithelial damage (91.4% and 76.8% vs. placebo, respectively, P<0.01) and goblet cell hyperplasia (67.4% and 50.1% vs. placebo, respectively, P<0.05), and decreased inflammatory cell influx (65.3% and 45.3% vs. placebo, respectively, P<0.01). CONCLUSION: Allergen challenge induces ROS in a tachykinin NK-1 receptor-dependent manner. Inhibition of the tachykinin NK-1 receptor reduces epithelial damage and subsequent remodelling in vivo. Therefore, patients may possibly benefit from treatment regime that includes radical scavengers or tachykinin NK-1 receptor antagonists.