Peste Des Petits Ruminants in Benin: Persistence of a Single Virus Genotype in the Country for Over 42 Years.

Peste des petits ruminants (PPR) is a contagious and often fatal disease affecting sheep and goats. Currently, it is endemic in Africa, the Middle and Near East, the Indian subcontinent and China. Understanding the molecular epidemiology and evolution of PPR virus (PPRV) can assist in the control of the transboundary spread of this economically important disease. We isolated PPRV from pathological and swab samples collected 42 years apart (1969 and 2011) in Benin, West Africa, and sequenced the full genome of two isolates (Benin/B1/1969 and Benin/10/2011). Phylogenetic analysis showed that all of the characterized isolates clustered within viral lineage II and that the 2011 isolates fell into two distinct subgroups. Comparison of the full genome sequences revealed a 95.3% identity at the nucleotide level, while at the protein level, the matrix protein was the most conserved between the two viruses with an identity of 99.7% and only one amino acid substitution over the 42-year sampling period. An analysis of specific amino acid residues of known or putative function did not identify any significant changes between the two viruses. A molecular clock analysis of complete PPRV genomes revealed that the lineage II viruses sampled here arose in the early 1960s and that these viruses have likely persisted in Benin since this time.

Relationship between cardiac tissue glycation and skin autofluorescence in patients with coronary artery disease.

AIM: During ageing, advanced glycation end-products (AGEs) accumulate in extracellular matrix proteins like collagen and contribute to a decline in organ function. As skin autofluorescence (sAF) can assess subcutaneous accumulation of fluorescent AGEs, this study aimed to investigate the relationship between AGE-modified cardiac tissue collagen and AGE-related sAF in coronary artery bypass graft (CABG) surgery patients. METHODS: Between January 2011 and January 2012, data from 72 consecutive male patients undergoing isolated CABG were prospectively recorded. Collagen fractions were isolated from the right atrial appendages of these patients by proteolysis and collagenase digestion. Collagen was quantified by hydroxyproline assay, and AGEs by AGE-related intrinsic fluorescence; sAF was measured using an autofluorescence reader. RESULTS: Biochemical analysis showed that the insoluble cardiac collagen fraction contained the highest amounts of accumulated AGEs; the AGE-related intrinsic fluorescence of this fraction increased with age (P=0.0001), blood glucose (P=0.002), HbA1c (P=0.01) and sAF (P=0.008). CONCLUSION: This study demonstrated for the first time a relationship between cardiac tissue glycation and AGE-related sAF. In addition, cardiac tissue glycation was associated with age, blood glucose and long-term glucose values in patients with coronary artery disease.

Full genome sequence of a peste des petits ruminants virus (PPRV) from Ghana.

The full genome of a peste des petits ruminants virus (PPRV) isolated from a sheep lung sample collected in Ghana, Western Africa, in 2010, has been sequenced. Phylogenetic analysis demonstrated that the virus clustered within the lineage II clade while comparison of its full genome with those of other PPRV strains revealed the highest identity (96.6 %) at a nucleotide level with the PPRV strain Nigeria/76/1. This is the first full genome sequence generated for a PPRV lineage II isolated since 1976.

Intraoperative sRAGE kinetics. A new age-related outcome predictor of cardiac surgery.

BACKGROUND: Glycated proteins (advanced glycation endproducts, AGE) in tissue are associated with degenerative diseases. This study evaluated the role of sRAGE (soluble receptor for advanced glycation endproducts), a decoy receptor of AGEs in blood, for the outcome of patients after coronary artery bypass grafting (CABG). METHODS: A total of 90 patients undergoing CABG were analysed in two centres. Perioperative blood samples were collected before surgery up to 1 week postoperatively. sRAGE was measured by ELISA. Patients were subdivided regarding age (< 64 versus > 70 years, 14 % versus 35 % female), euroSCORE (< 3 versus > 4, 14 % versus 29 % female) and sRAGE changes between sternotomy and end of the operation (< 30 % versus > 45 %, 33 % versus 33 % female) and subsequently analysed with respect of postoperative outcome parameters. RESULTS: Preoperative sRAGE values did not correlate with the outcome of the patients. sRAGE levels increase within 10 min from 1,539 ± 96 to 5,311 ± 187 pg/ml after sternotomy, then returning to baseline levels within 2 days after surgery. Comparing the analysed possible risk factors age, euroSCORE and sRAGE changes, no difference was observed regarding 30-day mortality. Age and the euroSCORE are superior with respect of tachyarrythmia, whereas sRAGE kinetics seems to be superior with respect of prolonged postoperative respiration time/stay in the intensive care unit or catecholamine support. CONCLUSION: A prolonged, increased intraoperative sRAGE level is a new outcome predictor for patients undergoing CABG surgery, mutually complementary to the euroSCORE.

First experiences with a combined usage of veno-arterial and veno-venous ECMO in therapy-refractory cardiogenic shock patients with cerebral hypoxemia.

The use of extracorporeal membrane oxygenation (ECMO) is becoming a popular tool in the treatment of cardiogenic shock. We present two case reports where classical veno-arterial peripherally cannulated ECMO therapy proved insufficient with profuse cerebral hypoxemia. After augmenting the setting into veno-veno-arterial ECMO, we achieved a remarkable improvement of all oxygenation parameters. The simultaneous use of veno-venous and veno-arterial ECMO might display as a novel strategy to counteract the coronary and cerebral hypoxemia in veno-arterial ECMO therapy in patients with therapy-refractory cardiogenic shock or in combined cardiopulmonary failure. In this manuscript, the veno-veno-arterial ECMO setup is described in full detail and different venous cannulas are discussed.

Immediate effects of individualized heparin and protamine management on hemostatic activation and platelet function in adult patients undergoing cardiac surgery with tranexamic acid antifibrinolytic therapy.

OBJECTIVE: This randomized prospective study was initiated to clarify whether individualized heparin and protamine dosing has immediate effects on hemostatic activation and platelet function in adult cardiac surgery. METHODS: Sixty adults undergoing elective coronary artery bypass grafting (CABG) were assigned to receive individualized heparin and protamine (HMS group, n= 29) or a standard dose (ACT group, n=24). Measures of thrombin generation and Multiplate (Verum Diagnostica, Munich, Germany) platelet function tests were performed before and after cardiopulmonary bypass (CPB). RESULTS: HMS patients received higher heparin (p = 0.006) and lower protamine (p<0.001) doses. Post-CPB, HMS managed patients showed significantly lower thrombin generation (thrombin-antithrombin (TAT) p<0.02) than the ACT group. Moreover, HMS managed patients had a better preservation of platelet function (COL p = 0.013; ADP p = 0.04; TRAP p = 0.04). CONCLUSION: An individualized and stable heparin concentration and appropriate dosing of protamine can reduce thrombin generation and preserve platelet function, even in short-time CPB.

The effect of an AGE-rich dietary extract on the activation of NF-κB depends on the cell model used.

Advanced glycation end products (AGEs) are the results of a chemical reaction of reactive aldehydes, such as sugars, with amino acid side chains. AGEs can be formed by the heating process of the food and taken up with the diet. They are thought to be at least in part responsible for major complications in age-related diseases. The activation of the transcription factor NF-κB plays a prominent role in AGE-induced cell signaling. This study aimed to elucidate the effect of exogenous AGEs on NF-κB activation in different cell models. Therefore a bread crust extract commonly found in a Western diet was chosen as an AGE-rich sample. Using RP-HPLC, 23 fractions from the bread crust extract were obtained. The immunodetection with specific antibodies for N-carboxymethyllysine arg-pyrimidine, pentosidine and 3-deoxyglucosone-imidazolone showed that the majority of the AGEs were located in the late fractions. Three different NF-κB reporter cell lines including NF-κB/293/GFP-Luc™, NF-κB/Jurkat/GFP™ and RAW/NF-κB/SEAPorter™ were stimulated with the 23 fractions. There was no direct correlation between the AGE content in the fractions and the cell activation. Whereas in Jurkat-T-cells, the stimulation seems to correlate at least in part with the AGE content, in HEK-293 epithelial cell nearly all fractions can stimulate NF-κB. In macrophages few fractions stimulate NF-κB whereas some fractions even inhibit the p38 MAP kinase. The highest expression of the AGE receptors like RAGE, AGER-1, AGER-2 and AGER-3 was detected in the macrophage RAW cell line. In conclusion the present study showed a new approach to study bioactive compounds in bread crust extract. The identification of the bioactive compounds is still ongoing.

Surgical site infections after coronary artery bypass graft surgery: incidence, perioperative hospital stay, readmissions, and revision surgeries.

PURPOSE: High-tech operations performed in cardiac surgery are associated with an increased risk of surgical site infections. In this study, we investigated if surgical site infections following cardiac surgery influence revision surgeries and patients' length of stay, and compared the results to German hospital infection surveillance data. METHODS: Over a period of 3 years, 2,621 patients of a cardiac surgery unit were enrolled following cardiac artery bypass graft surgery. Patients were examined for the incidence of surgical site infections, revision surgeries, and length of stay. The results were compared to the National Reference Center (NRC) data retrospectively. RESULTS: Of the observed population, 4.5 % suffer from surgical site infections, and in 7.7 % of the patients, revision surgery had to be performed. The length of stay was exceeded significantly for the patients with surgical site infections (average stay 14.5 vs. 42.2 days, p < 0.001). Compared to the NRC data, severe surgical site infections were not increased significantly. CONCLUSION: Surgical site infections resulted in revision surgeries with a significantly increased inpatient stay. However, this increase did not differ significantly from comparable German university hospitals.

RAGE influences obesity in mice. Effects of the presence of RAGE on weight gain, AGE accumulation, and insulin levels in mice on a high fat diet.

BACKGROUND: The metabolic syndrome is defined by the presence of obesity, insulin resistance, dyslipidemia, and hypertension. Advanced glycation end products (AGEs) are stable end products of the Maillard reaction, whereby AGE accumulation is considered not only a biomarker of aging but is also associated with several degenerative diseases. AGEs are recognized by several receptor molecules of which the receptor of AGEs (RAGE) is currently the most intensively studied receptor. Activation of RAGE causes an unfavorable proinflammatory state and deletion of RAGE in diabetic animals has been reported to protect against atherosclerosis. AGEs and a high fat diet are associated with cardiovascular diseases, whereas is still not clear whether a direct link between high fat nutrition and AGEs exists in vivo. MATERIALS AND METHODS: C57BL/6 and C57BL/6 RAGE -/- mice were fed a high fat diet to induce obesity. Weight, insulin, lipid levels, AGE modifications, and cardiac gene expression were analyzed. RESULTS: The absence of RAGE resulted in accelerated weight gain, increased plasma cholesterol, and higher insulin levels in obese mice. The hearts of normal and obese RAGE -/- mice contained lower levels of the AGE arginine-pyrimidine and 3DG-imidazolone than RAGE + / + animals. RAGE -/- mice also exhibited lower expression of the genes encoding the antioxidative enzymes MnSOD, Cu/ZnSOD, and ceruloplasmin in cardiac tissue, whereas the AGE receptors AGER-1, -2, and -3 were equally expressed in both genotypes. Obese mice of both strains expressed increased amounts of AGER-2. Only obese RAGE + / + mice exhibited a reduced mRNA accumulation of Cu/Zn SOD. CONCLUSION: These data suggest that RAGE is involved in the development of obesity and insulin resistance.

[Prophylactic intraaortic balloon pumping in high-risk cardiac surgery patients]. / Prophylaktische intraaortale Ballongegenpulsation bei herzchirurgischen Hochrisikopatienten.

BACKGROUND: We examined the impact of prophylactic IABP insertion in EuroSCORE-stratified high-risk cardiac surgery patients with a score ≥8. MATERIAL AND METHODS: A randomized trial with 104 patients either without prophylactic IABP insertion (group A, n=52) or with IABP (group B, n=52) was conducted. The primary endpoint was 30-day mortality. RESULTS: The median age of the patients was 74 years and 43% of participants were females. The 30-day mortality did not differ between group A (17.3%) and group B (13.4%; p=0.78). The median hospital stay was 14 days in both groups. Intra- and postoperative IABP support was required by 13 patients (21%) in group A. The median ventilation time (14 hours versus 13 hours), median catecholamine dose, frequency of dialysis-dependent acute renal failure (28% versus 18%), cardiac indices, and frequency of a low cardiac output syndrome (26% versus 25%) did not significantly differ between groups. CONCLUSION: Prophylactic preoperative IABP insertion in EuroSCORE-stratified high-risk patients is not associated with decreased 30-day mortality.

Inflammatory response in on- versus off-pump myocardial revascularization: is ECC really the culprit?

A review of inflammatory mediators in on- versus off-pump surgery reveals that parameters of systemic inflammation differ quantitatively, not qualitatively between these approaches. Mediator system and cellular activation is observed after surgical trauma and following ischemia/reperfusion. Such activation is also modulated by genetic factors. The available literature does not permit definitive conclusions to be made on the advantages of off-pump surgery with respect to the systemic inflammatory response. The relationship between mediator systems and clinical course needs to be assessed in large patient populations to demonstrate to what extent off-pump surgery is more than just theoretically superior to on-pump surgery.

Dicarbonyl-mediated protein modifications affect matrix metalloproteinase (MMP) activity.

Advanced age is linked with an increased incidence of epithelial tumours (carcinomas) including lung tumours. However, a slowing rate of the increase of age-specific cancer incidence is demonstrated at very advanced ages, and elderly patients also develop less invasive and metastatic tumours than their younger counterparts. Matrix metalloproteinases (MMPs) are commonly upregulated in the stromal compartment of the carcinoma tissue and are believed to promote invasion and metastasis. As the increased serum and tissue level of advanced glycation end products (AGEs) is a characteristic feature of old humans, our study focused on the impact of AGEs on the activity of MMPs released from lung fibroblasts (WI- 38). The collagen gel zymography technique showed the primary presence of MMP-2 in the conditioned medium of the WI-38 fibroblasts, which was even higher in senescent WI-38 fibroblasts. Subsequent treatment of the WI- 38 conditioned medium with the dicarbonyl compound glyoxal, a highly reactive precursor of the AGE formation, resulted in a dose-dependent reduction of the MMP-2 activity. Therefore, our study suggests that the age-associated increase in AGEs might be one potential host factor responsible for the less invasiveness of tumours at very advanced age.

Advanced glycation end products, diabetes and ageing.

Advanced glycation end products (AGEs) are formed in vivo by a non-enzymatic reaction of proteins with carbohydrates and accumulate in many tissues during ageing. They are discussed as being responsible for many age- and diabetes-related diseases. On the other hand, AGEs are formed by the heating of food and are taken up by the nutrition. The contribution of endogenously formed versus exogenous intake of AGEs to age-related diseases is still under discussion.

Advanced glycation endproducts: a biomarker for age as an outcome predictor after cardiac surgery?

OBJECTIVE: A decline in the function of all organs can be detected during ageing. Although the trend appears to be stable, deviation within the elderly population is much greater in comparison to young controls. The aim of the study was to identify a marker of senescence which correlates to heart function. Advanced glycation endproducts (AGEs) accumulate with age and are associated with degenerative diseases. METHODS: Carboxymethyllysine (CML) concentrations in the pericardial fluid (as a measure of AGEs) were analysed with ELISA technique in 75 patients undergoing cardiac surgery and correlated with clinical parameters and outcome of these patients. RESULTS: CML content of pericardial fluid increases significantly with age. AGEs show an inverse correlation to left ventricular ejection fraction. High CML levels correlate with poor outcome of patients as shown by adverse cardiac events, prolonged ventilation time and prolonged stay within the Intensive Care Unit. Within all parameters, AGE concentration of the pericardial fluid fits better with the outcome of the patients in comparison to age alone. Interestingly, medical treatment with nitrates correlates with increased CML content. CONCLUSION: AGEs, in addition to being a marker of senescence, appear to represent a prognostic factor in cardiac surgery, which can be used as a predictor of patient outcome.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) restores decreased monocyte HLA-DR expression after cardiopulmonary bypass.

OBJECTIVES: Cardiopulmonary bypass (CPB) is associated with a disturbed immune response, e.g., impaired HLA-DR expression on monocytes and the release of pro- and anti-inflammatory cytokines. Cytokine release plays a role in the pathogenesis of postoperative systemic inflammatory response syndrome (SIRS) and immune system deterioration, e.g., impaired monocyte and polymorphonuclear neutrophil (PMN) function, factors that ultimately lead to an increased susceptibility to infections. To gain a further understanding, we investigated HLA-DR expression on monocytes and on B- and T-lymphocytes. In addition, we investigated the IN VITRO effect of the immunostimulating hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) on HLA-DR expression of these cell types. Neither HLA-DR expression on B- and T-lymphocytes nor the effects of GM-CSF in cardiac surgical patients have been studied before. METHODS: In 16 patients undergoing elective cardiac surgery with CPB, counts of circulating leukocyte subsets as well as HLA-DR expression on monocytes, B- and T-lymphocytes were measured by flow cytometry before, immediately after CPB, and on the 2nd and 10th postoperative days. Treatment with GM-CSF was performed IN VITRO in whole blood cultures with 100 ng/ml recombinant human GM-CSF for 20 h. RESULTS: Monocyte HLA-DR expression was attenuated immediately after CPB (125 +/- 4 mean channel fluorescence [MCF] vs. 143 +/- 2 MCF preoperatively, mean +/- SEM, P < 0.001). HLA-DR expression further decreased on the 2nd day after CPB and did not normalize until the 10th day after the operation. In contrast, HLA-DR expression on T-cells was unchanged, whereas HLA-DR expression on B-cells did not decrease before the 2nd day after CPB (152 +/- 3 MCF vs. 170 +/- 2 MCF preoperatively, P < 0.001). IN VITRO GM-CSF treatment increased HLA-DR expression on monocytes prepared after CPB to a degree comparable to preoperative values. HLA-DR expression on B-lymphocytes could not be restored by GM-CSF. CONCLUSIONS: Immune system suppression after cardiac surgery is reflected in prolonged diminished HLA-DR expression on monocytes and B-lymphocytes. Suppression is not irreversible but can - at least IN VITRO - be overridden by the immunostimulating compound GM-CSF.

[Telemedical monitoring of electrocardiograms after cardiac surgery--results from a pilot study among 208 patients]. / Telemedizinisches EKG-Monitoring nach herzchirurgischen Operationen: Ergebnisse einer Pilotstudie mit 208 Patienten.

BACKGROUND: An increasing number of older patients undergo cardiac surgery. Complications after cardiac surgery such as rhythm disorders, myocardial infarction and atypical symptoms frequently lead to ambulatory visits and hospitalisations. Telemonitoring might be one method for rapid and efficient detection and classification of symptoms. We examined in this pilot study if ECG-telemonitoring after cardiac surgery proves to be an useful, reliable and accepted procedure with respect to cost and risk reduction. METHODS & RESULTS: Two hundred eight patients (46 female, 162 male) received after surgery an individually adjusted portable 12-lead ECG-monitor. Within three months all incoming ECG-recordings were analysed. In total, 1387 calls from 165 patients (80% use) with ECG-recording (8,4 calls per patient) were collected. There were 235 calls (17%) because of symptoms, 51% of them were registered between 6 PM and 8 AM. Fourteen (6%) out of those 235 emergency calls with ECG-registration led to hospitalisation (n=5) or ambulatory visits next day. The remaining 221 ECG showed no pathological ECG-signs and the patients could be managed with telephonic advice, reassurance and telemedical follow up. Readmissions were due to angina pectoris, severe but unspecific chest pain and cardiac decompensation (n=3) as well as rhythm disturbances (n=2). Almost 75% of all emergency calls were recorded within the first 60 min after the onset of symptoms. CONCLUSION: Older patients reproducibly are able to telemetrically transmit electrocardiograms after a short training before discharged home. Although there is a low incidence of complications among our study population, telemedical ECG-monitoring rapidly helps to differentiate between the symptoms leading to increased patient safety and prevented further damage. The reduction of ambulatory visits and hospitalisations only for treatment of objectified symptoms may lead to a overall cost reduction in the health care system. The reduction of unnecessary hospitalisations and ambulatory visits might also contribute to an optimised time management.

RAGE: a new pleiotropic antagonistic gene?

Advanced glycation end products (AGEs) are the result of a nonenzymatic reaction of reducing sugars with primary amino groups of proteins (Maillard reaction). They accumulate in various tissues in the course of aging. Because AGEs induce protein cross-links and oxidative stress (radicals) within cells and tissues, they have been implicated in the development of many degenerative diseases. Binding of AGEs to receptors like RAGE induces the release of profibrotic cytokines, such as TGF-beta or proinflammatory cytokines, such as TNF-alpha or IL-6. AGE inhibitors or breakers, such as aminoguanidine or ALT-711, inhibit the age-induced heart hypertrophy or stiffness of the large arteries. On the other hand, little is known about the physiological role of RAGE as the receptor of AGEs. Investigations about the expression of RAGE in lung tissue and lung tumors may give a hint for such a role.

[Severe, non-infectious mitral valve endocarditis after mitral valve reconstruction in a 32-year old female with primary antiphospholipid syndrome]. / Schwere, nicht-infektiöse Mitralklappenendokarditis nach Klappenrekonstruktion bei einer 32-jährigen Patientin mit primärem Antiphospholipid-Syndrom.

BACKGROUND: A 32-year old female with primary antiphospholipid syndrome presented 8 months after mitral valve reconstruction with progressive exertional dyspnea and echocardiographically demonstrable critical mitral stenosis and regurgitation. Tachycardia, weight loss, sleep disturbances and increasing nervosity led to the diagnosis of concomitant hyperthyroidism. After the patient stopped the oral anticoagulation by herself, a 'catastrophic antiphospholipid syndrome' with multiple microthromboembolic events in several organs developed rapidly within a few weeks. Severe respiratory failure was observed 14 days after admission at our hospital because of a pulmonary edema. TREATMENT: Removal of the annuloplasty ring and alloplastic mitral valve replacement with a 25 mm bilifleat valve. Postoperatively, the patient was placed on oral anticoagulation. Several pre- and postoperative plasmaphereses lowered the level of antiphospholipid antibodies. The patient additionally underwent radioiodtherapy 5 months postoperatively. RESULTS: While hemodynamics and diuresis remained sufficient, ventilatory support with tracheostomy was necessary for 16 postoperative days to achieve stable respiration. Thirty months later, the patient is well and without further cardiac and neurological dysfunction. CONCLUSION: Secondary cardiac valve operations on patients with primary antiphospholipid syndrome may be successfully performed within a multidisciplinary approach. Oral anticoagulation remains the treatment of choice to prevent further thromboembolic events.

Age-dependent expression of advanced glycation end product receptor genes in the human heart.

BACKGROUND: Advanced glycation end products (AGEs) are formed by the reaction of sugars and NH2 groups of lysine and arginine residues and have been shown to accumulate in tissues, including the heart, with normal ageing. The interaction of AGEs with their receptors is known to cause changes in cell function, leading, for example, to the production of pro-inflammatory cytokines and free radicals. OBJECTIVE: This study investigated the gene expression of the five known AGE receptors: AGE-R1, AGE-R2, AGE-R3, the scavenger receptor II, and the receptor for AGEs (RAGE) in human heart tissue. METHODS: Tissue samples were taken from the right cardiac auricles from three patient groups: children (2.4 +/- 1.1 years), adults (45.3 +/- 0.8 years) and elderly subjects (76.4 +/- 0.4 years). Analysis of gene expression of the five AGE receptors was performed using the reverse transcription-polymerase chain reaction (RT-PCR) and 18S mRNA levels as loading controls. RESULTS: Our results show an age-dependent upregulation of the genes for AGE-R3 and the scavenger receptor II, but a downregulation for RAGE and no significant differences for AGE-R1 and AGE-R2. CONCLUSION: This study supports a pathophysiological function for AGE receptors such as AGE-R3 and RAGE in the ageing heart.

Cardiovascular multimorbidity, emerging coalescence of the integrated panvascular approach.

Cardiovascular diseases are systemic processes frequently involving multiple vascular beds. Cardiovascular multimorbidity, arbitrarily defined as a clinically relevant disease of at least two major vascular beds in a single individual is frequent occurring in 30% to 70% of patients depending on the patient population. Management of patients with cardiovascular multimorbidity is complex requiring an interdisciplinary consensus and coordination. A panvascular concept of an interdisciplinary integrated management of these patients is introduced.