Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

Acute outcome of chronic total occlusion (CTO) recanalizsation in the elderly.

OBJECTIVES: Percutaneous coronary intervention (PCI) of total chronic total occlusion (CTO) still remains a major challenge in interventional cardiology. There is only insignificant knowledge reported in the literature about age differences in CTO recanalization. We analyzed in this study the issue of the impact of age on procedural characteristics, complications and short-term outcome. METHODS: Between 2012-2016 we included 440 patients. They underwent PCI for at least one CTO. Antegrade and retrograde CTO techniques were applied. The retrograde approach was used only after failed antegrade intervention. Continuous data are presented as the mean ± standard deviation; categorical data are presented as numbers and percentages unless otherwise specified. We used Twosamplet- t-test with equal variance to test the significant differences of the variables between the two cohorts. RESULTS: Procedural success proved independently of age. There was no significant interaction between age and procedural success (p=0.5). Complication rates were low in both groups (2.7% vs. 4%; p=0,4) with no difference in statistical significance. CONCLUSIONS: Our study suggests that in an aging society patients with severe coronary artery disease and chronical total occlusions an interventional therapy should be used more intensively. It can be performed safe and feasible.

Vagal heart rate control in patients with atrial fibrillation: impact of tonic activation of peripheral chemosensory function in heart failure.

Heart failure (HF) and atrial fibrillation (AF), emerging as two epidemics of the twenty-first century, are commonly associated with each other. Both have been mechanistically linked to changes in cardiac vagal control. The importance of peripheral chemosensors, located in the carotid body, has not been elucidated so far. We therefore investigated whether tonic activation of excitatory chemoreceptor afferents contributes to the altered vagal control in HF patients with a history of AF. In 18 patients (72 ±9 year, 7 male) with sinus rhythm and a history of AF (n=9, without any evidence of structural heart disease, AF group; n=9 with structural heart disease and clinical presentation of HF, AFHF group) we investigated the impact of chemosensory deactivation (by breathing 100% oxygen) on heart rate, blood pressure, cardiac output, total peripheral resistance, oxygen saturation and breathing rate. Ten healthy individuals served as a control group. In addition, we performed a deep breathing test demonstrating an impaired heart rate variation in patients with and without HF as compared with controls (expiration/inspiration difference: 23.9±6.9 vs. 6.9±6.1 bpm, and 23.9±6.9 vs. 7.8±4.8 bpm; p<0.05). In both control and AF groups, heart rate decreased during chemoreceptor deactivation (control: -4.8±3.4%; AF: -5.1±3.0%; p<0.05), whereas heart rate did not change in AFHF patients. This resulted in impaired cardiac chemoreflex sensitivity in AFHF patients (1.9±1.6 vs. 0.5±1.2 ms/mmHg; p<0.05). In conclusion, our data suggest that tonic activation of excitatory chemoreceptor afferents contributes to a low vagal tone in heart failure patients with a history of AF (Clinical Trials NCT01262508).

Validity of the J-CTO Score and the CL-Score for predicting successful CTO recanalization.

BACKGROUND: Percutaneous coronary intervention (PCI) of total chronic coronary occlusion (CTO) still remains a major challenge in interventional cardiology. To predict the probability of a successful intervention different scoring systems are available. We analyzed in this study the validity of two scoring systems, the Japanese CTO score (J-CTO score) and the newly developed Clinical and Lesion-related score (CL Score). METHODS: Between 2012 and 2015 we included 379 consecutive patients. They underwent PCI for at least one CTO. Antegrade and retrograde CTO techniques were applied. The retrograde approach was used only after failed antegrade intervention. RESULTS: Patients undergoing CTO PCI were mainly men (84%). The overall procedural success rate was 84% (±0.4). The mean J-CTO score was 2.9 (±1.3) and the mean CL score was 4.3 (±1.7). The CL score predicted more precisely the interventional results than the J-CTO score. CONCLUSIONS: Our study suggests that the previously presented CL score is superior to the J-CTO score in identifying CTO lesions with a likelihood for successful recanalization. Generally it appears to be a helpful tool for selecting patients and identifying the appropriate operator.

Low-power hybrid wireless network for monitoring infant incubators.

We have created a pilot wireless network for the convenient monitoring of temperature and humidity of infant incubators. This system combines infrared and radio frequency (RF) communication in order to minimize the power consumption of slave devices, and we therefore call it a hybrid wireless network. The slave module installed in the infant incubator receives the calling signal from the host with an infrared receiver, and sends temperature and humidity data to the host with an RF transmitter. The power consumption of the host system is not critical, and hence it uses the maximum power of infrared transmission and continuously operating RF receiver. In our test implementation, we included four slave devices. The PC calls each slave device every second and then waits for 6 s, resulting in a total scan period of 10 s. Slave devices receive the calling signals and transmit three data values (temperature, moisture, and skin temperature); their power demand is 1 mW, and can run for about 1000 h on four AA-size nickel-hydride batteries.

[AV nodal reentrant tachycardia. Diagnosis and therapy]. / AV-Knoten-Reentrytachykardie. Diagnostik und Therapie.

The AV nodal reentrant tachycardia (AVNRT) is one of the most common arrhythmias encountered in clinical practice. It is characterized by a constant heart rate and an on/off phenomenon. The clinical symptoms may include palpitations, anxiety, polyuria, and dyspnea. Typically, tachycardia may be disrupted by vagal maneuvers in many patients. First-line treatment of symptomatic AVNRT is radiofrequency ablation. The present article deals with the characteristics, differential diagnosis and treatment of AVNRT in the EP lab. It is the second part of a series of manuscripts which may facilitate further education in the specific field of electrophysiology.

[How to approach the patient with supraventricular tachycardia in the EP lab: A systematic overview]. / Diagnostik bei supraventrikulären Tachykardien : Wie ist das Vorgehen im elektrophysiologischen Labor?

The term supraventricular tachycardia (SVT) summarizes those tachycardias involving the atrial myocardium along with the atrioventricular (AV) node. The prevalence is about 2.25 per 1000 (without atrial fibrillation and atrial flutter) and, therefore, SVT represents one of the most common group of arrhythmias besides atrial fibrillation encountered in the emergency department especially since they tend to recur until definite therapy. The clinical symptoms may include palpitations, anxiety, presyncope, angina, and dyspnea. Pharmacological therapy of these arrhythmias often fails. The present article deals with the differential diagnosis of SVT and also introduces a series of manuscripts that provide detailed insight into the differential diagnosis and treatment of these arrhythmias.

In vitro function of S rnases in Lycopersicon peruvianum.

S RNases are products of the S locus that are expressed in the stylar tissue of Lycopersicon peruvianum with the gametophytic self-incompatibility (SI) system. Two S RNases (S12 and Sa) with RNase activity from the S12Sa genotype of L. peruvianum were purified using gel filtration and cation-exchange chromatography. The molecular masses of the two RNases, S12 and Sa, were 21 and 23.1 kDa, respectively. The specific activities of S12 and Sa for torula yeast rRNA as a substrate were 8,500 and 6,000 units/ml, respectively. Of various reagents tested for RNase activities, ZnSO4 and CuSO4 were found to remarkably reduce its activity. The growth of S12Sa pollen was inhibited when it was cultured in a pollen germination medium that contained the purified S12 RNase. The result suggested that the S RNase was either a probable inhibitor of pollen growth or controlled pollen growth. Additionally, 512Sa pollens germinated well in vitro in a germination medium that contained S12 RNase in the presence of ZnSO4 and CuSO4. Our finding suggests that the treatment of S RNase with its inhibitor destroys the SI ability on an in vitro self-pollen growth test.

Web-based remote monitoring of infant incubators in the ICU.

A web-based real-time operating, management, and monitoring system for checking temperature and humidity within infant incubators using the Intranet has been developed and installed in the infant Intensive Care Unit (ICU). We have created a pilot system which has a temperature and humidity sensor and a measuring module in each incubator, which is connected to a web-server board via an RS485 port. The system transmits signals using standard web-based TCP/IP so that users can access the system from any Internet-connected personal computer in the hospital. Using this method, the system gathers temperature and humidity data transmitted from the measuring modules via the RS485 port on the web-server board and creates a web document containing these data. The system manager can maintain centralized supervisory monitoring of the situations in all incubators while sitting within the infant ICU at a work space equipped with a personal computer. The system can be set to monitor unusual circumstances and to emit an alarm signal expressed as a sound or a light on a measuring module connected to the related incubator. If the system is configured with a large number of incubators connected to a centralized supervisory monitoring station, it will improve convenience and assure meaningful improvement in response to incidents that require intervention.

Predictors of sustained ventricular arrhythmia episodes in patients with primary ICD indication: male gender and AF in primary ICD prophylaxis.

AIMS: Implantable cardioverter-defibrillators (ICD) reduce mortality in patients with severely impaired left ventricular function. In randomized studies, female patients are underrepresented and data on ICD therapy is limited. Atrial fibrillation (AF) is a determinant of poor prognosis but has not been consistently evaluated. We evaluated the risk factors for the occurrence of ventricular arrhythmia episodes in patients with primary ICD prophylaxis. METHODS: Consecutive patients after ICD implantation for primary prophylaxis were followed. During follow-up, detected sustained episodes of ventricular arrhythmia were documented. Multivariate analysis controlled for propensity score was used to evaluate the correlation between gender, history of AF, and the occurrence of ventricular arrhythmia episodes. RESULTS: A total of 400 patients (19.8% female; n = 79) were included. During follow-up, 64 patients (16%) had appropriate ICD therapy episodes. Men (18%) had significantly more often episodes than women (8%; p = 0.025). Patients with a history of AF (102, 25.5%) had significantly more often episodes (30%) compared to patients without a history of AF (11%; p < 0.001). In a multivariate model, only gender (p = 0.02) and history of AF (p < 0.001) were significantly associated predictors of the occurrence of appropriate ICD therapies during follow-up. Based on the propensity score model, the adjusted hazard ratio for male gender was 2.7 (p = 0.02) and 2.6 (p = 0.0004) for history of AF. CONCLUSION: Male gender and history of AF are independent predictors for the occurrence of sustained ventricular arrhythmia in primary ICD prophylaxis. Further studies need to evaluate whether history of AF in female patients might be an indicator for higher risk of sudden cardiac arrhythmic death.

[Recurrent ventricular tachycardias following myocardial infarction: linear ablation strategy using an electroanatomical mapping system]. / Rezidivierende ventrikuläre Tachykardien nach Myokardinfarkt: Lineare Ablationsstrategie unter Einsatz eines elektroanatomischen Mappingsystems.

BACKGROUND AND AIM OF STUDY: The implantable cardioverter defibrillator (ICD) is the therapy of choice for patients with ventricular tachycardia (VT) after myocardial infarction. In some patients frequent ICD shocks occur, often resulting in clinical problems, if antiarrhythmic drugs insufficiently suppress them. Our aim was to describe electro-anatomical mapping and ablation techniques in patients with VTs, in which conventional strategy treatments have failed. PATIENTS AND METHODS: 17 patients (69.5 +/- 8 years, 12 male) were included. During 3 months before ablation the number of ICD shocks was 21 +/- 8 (mean +/- SD). Using an electro-anatomical mapping system (CARTO), activation mapping was performed in 12 patients during hemodynamically tolerable, stable VT. In 5 cases with "non-mappable" VT only voltage mapping during sinus rhythm was obtained. The aim was to characterize the underlying scar tissue precisely in order to modify the substrate with an individual strategic linear lesion, thus preventing re-induction of VT. RESULTS: Procedure time was 184 +/- 9 minutes, fluoroscopy time totalled 19 +/- 9 minutes. Lesion lines were established with 13 +/- 9 ablation pulses. In 15 patients (88 %) acute ablation of the VT was successful. During a follow-up of 8 +/- 7 months, 2 patients had a recurrence of the VT. Two patients developed a VT with a different morphology. In another case ventricular fibrillation occurred. No major complications were observed. CONCLUSION: Electro-anatomical mapping combined with an individual linear ablation strategy is a safe and effective method to prevent symptomatic VT in patients after myocardial infarction.

Plasma levels of NT-pro-BNP in patients with atrial fibrillation before and after electrical cardioversion.

OBJECTIVE: Plasma levels of brain natriuretic peptide (BNP) have been examined in studies on patients with persistent atrial fibrillation, both before and after electrical cardioversion. Studied patients often showed a comorbidity with congestive heart failure, which complicates interpretation of measured BNP values as a natriuretic peptide. The aim of this study was to examine plasma levels of N-terminal fragment pro-brain natriuretic peptide (NT-pro-BNP), which is the more stable but inactive cleavage product of pro-BNP in patients with atrial fibrillation, but normal left ventricular ejection fraction, before and after electrical cardioversion. PATIENTS AND METHODS: NT-pro-BNP plasma levels of 34 consecutive patients were measured before, shortly after and 11 days after electrical cardioversion. All patients showed a normal ejection fraction after echocardiographic or laevocardiographic criteria. RESULTS: At baseline, all patients showed elevated NT-pro-BNP compared to a healthy control group (1086 vs. 66.9 pg/ml, p<0.001). After a mean follow-up time of 11 days in patients with persistent restored sinusrhythm, NT-pro-BNP decreased from 1071 pg/ml at baseline to 300 pg/ml (p<0.001). In contrast, patients with recurrence of atrial fibrillation showed increased levels from 1570.5 pg/ml at baseline to 1991 pg/ml (p=0.13; n.s.). Recurrence of atrial fibrillation was independent from height of NT-pro-BNP levels at baseline (p=0.23). CONCLUSIONS: Atrial fibrillation in patients with a normal left ventricular ejection fraction is associated with elevated NT-pro-BNP plasma levels, which decrease when a persistent sinus-rhythm can be restored by electrical cardioversion. On the other hand, NT-pro-BNP seems to increase (n.s.) when recurrence of atrial fibrillation occurs. Finally, NT-pro-BNP is no valid predictor for long-term success of sinus-rhythm restoration by electrical cardioversion.

Tissue culture responses of explants taken from branch sources with different degrees of juvenility in mature black locust (Robinia pseudoacacia) trees.

We studied the in vitro responses of cambial tissue and dormant vegetative buds obtained from top and epicormic branches of three mature black locust (Robinia pseudoacacia L.) trees. Cambial tissues isolated from epicormic branches produced more callus than cambial tissues isolated from top branches, whereas in vitro shoot cultures derived from buds excised from top branches grew faster than those derived from buds excised from epicormic branches. There were no significant differences between the two branch sources in in vitro bud break or shoot multiplication from bud explants or cambial-derived callus tissue, respectively. Furthermore, the top branches, generally considered to be the most mature in a tree, were not recalcitrant in terms of morphogenic capacity compared to epicormic branches.

The influence of gastrectomy on the change of bone metabolism and bone density.

OBJECTIVES: Abnormalities of bone metabolism could be followed in gastrectomized patients as a late complication. Nowadays, many biochemical and radiologic measurements are applied to detect these abnormalities. The aim of our study is to determine the valuable parameter as an appropriate screening test during long-term follow-up periods and define the usefulness of new biochemical markers for bone metabolism by comparing with traditional markers. METHODS: Fifteen patients who had undergone partial gastrectomy were chosen randomly and fifteen healthy controls were compared. Then, several biochemical and radiologic tests were measured. We excluded subjects who proved to have other causes of bone metabolism abnormalities. Ten patients and 10 controls were finally selected. RESULTS: Comparing the data with those of a corresponding control group, the lumbar bone density measured by quantitative computed tomography (QCT) was statistically significantly lower in the patient group (p < 0.01). The urinary deoxypyridinoline, a biochemical marker for bone resorption, was statistically higher in the patient group (p < 0.025). Osteocalcin, Procollagen I C-terminal peptide (PICP) and Type I collagen C-terminal telopeptide (ICTP) were slightly but not significantly higher in the patient group. The serum parathyroid hormone (PTH) and 25-hydroxy vitamin D levels were similar in both groups. CONCLUSION: We could suggest that urinary deoxypyridinoline and QCT are appropriate parameters as screening tests for the detection of bone metabolism abnormalities in gastrectomized patients during long-term follow-up. Urinary deoxypyridinoline may be a simple and rapid test which could replace cumbersome 24-hour urinary hydroxyproline.

Co-operation of IL-1 and IL-2 on T-cell activation in mononuclear cell cultures.

In search of an optimized anti-cancer immunotherapy, the combination of IL-2 and IL-1 has been tried. In an in-vitro LAK model, this cytokine cocktail seemed to be quite promising. In our in-vitro model of IL-2 induced T-cell activation we have therefore investigated the co-operation of these two potent immunostimulators. Mononuclear cells were stimulated with CD3 activating antibody in the presence of different cytokines and blocking or neutralizing antibodies. Cytokine concentrations were detected in the supernatants with ELISA. Intracellular IFN-gamma and IL-4 in the different T-cell subsets was measured by flow cytometry. IL-1 and IL-1 receptor antagonist (IL-1Ra) were up-regulated by IL-2, this was achieved independently of IL-12 or CD40/CD40L interaction. As a negative feedback mechanism, IL-1beta induced its natural antagonist, IL-1Ra. Both endogenous and exogenous IL-10 suppressed IL-1beta and induced IL-1Ra, thus markedly decreased the amount of functional IL-1. The combination of IL-2 and IL-1beta lead to a mildly increased Interferon-gamma (IFN-gamma) secretion (+20%, p < 0.05), however, this appeared to be the result of an increased IFN-gamma production per secreting cell, rather than of an increased recruitment of non-secreting cells. Similarly, IL-6 was also induced in an additive fashion (+30%, p < 0.05). For both cytokines, this effect could be significantly augmented by neutralizing IL-1Ra. Concentrations of IL-2 induced IL-10 and soluble Fas ligand (sFasL) were not affected by IL-1beta. We were thus able to demonstrate that IL-1 relays its activity through different pathways than IL-2. Furthermore, we could show that the potentially synergistic action of IL-2 and IL-1 was hindered by the simultaneous induction of signficant amounts of IL-1Ra. From the latter findings we conclude that the combination of IL-2 and IL-1 for cytokine-induced anti-tumor activity may not, but a combination of IL-2 and anti-IL-1Ra might prove beneficial.

[Therapy options for Prinzmetal angina induced ventricular vulnerability]. / Therapieoptionen einer Prinzmetal-Angina induzierten ventrikulären Vulnerabilität.

We report about a 46 year old male, who survived sudden cardiac death caused by recurrent ventricular tachycardia as the clinical manifestation of a vasospastic right coronary artery. After implantation of an implantable cardioverter defibrillator, the patient did not respond to conservative treatment despite of different drug therapies. Therefore, the vasospastic right coronary artery was treated by a percutaneous transluminal coronary angioplasty and stenting, which could not reduce the occurrence of further tachycardias. Finally, the patient underwent an operative myocardial revascularization combined with sympathectomy. During the whole follow-up of six months no new episodes of ventricular tachyarrhythmias have occurred.

Antihepatotoxic activity of icariin, a major constituent of Epimedium koreanum.

In an attempt to identify compounds with antihepatotoxic activity, carbon tetrachloride-induced cytotoxicity in primary cultured rat hepatocytes has been adopted as a screening system. Using this screening system, an antihepatotoxic compound from the aerial parts of Epimedium koreanum has been isolated. This compound, icariin, is a flavonol glycoside. Its antihepatotoxic activity was first evaluated by measuring the release of glutamic pyruvic transaminase and sorbitol dehydrogenase from CCl4-intoxicated rat hepatocytes into the culture medium. Icariin significantly reduced the level of glutamic pyruvic transaminase and sorbitol dehydrogenase released resulting in a 76% protection from toxicity at concentration ranges from 1 microM to 20 microM. The antihepatotoxic activity of icariin was also estimated by the determination of total cytochrome P-450 content and glutathione-S-transferase activity in the CCl4-intoxicated hepatocytes.

Cardiogenic shock due to thrombotic thrombocytopenic purpura.

We report the case of a 49-year-old man with thrombotic thrombocytopenic purpura (TTP) leading to cardiogenic shock. Laboratory data were typical for TTP with thrombocytopenia and microangiopathic hemolytic anemia. The electrocardiogram recorded significant ST-segment elevations in the anterior and inferior leads. In addition' coronary angiography showed normal epicardial coronary arteries with slow flow. The patient died due to electromechanical dissociation six hours after admission. During autopsy typical features of thrombotic thrombocytopenic purpura were found. Histological preparation of the heart showed a diffuse myocardial necrosis due to microvascular thrombosis. Cardiac involvement is common in TTP but extended myocardial necrosis has been reported in only a few cases.

Interleukin 10 inhibits TNF-alpha production in human monocytes independently of interleukin 12 and interleukin 1 beta.

Previously we demonstrated that endogenously produced Interleukin (IL-)10 suppressed the production of tumor necrosis factor-alpha (TNF-alpha) in CD3 activated T-cells via down-regulation of paracrine IL-12 secretion from APC. Here we investigated the effect of endogenous IL-10 on TNF-alpha production in purified lipopolysaccharide (LPS) stimulated monocytes and its mechanism. Similarly to its effects on T-cells, IL-10 inhibited monocyte TNF-alpha production by about half. Unlike in T-cells, however, this effect was not mediated via IL-12. While blockade of endogenous IL-10 binding to the IL-10 receptor enhanced the autocrine production of TNF-alpha, IL-12 and IL-1 beta, the neutralization of IL-12 or IL-1 beta did not affect the IL-10 effects on TNF-alpha production. This suggests that despite its inhibitory effects on IL-12 and IL-1 beta, which is quite similarly observed in T-cells, in purified monocytes IL-10 does not effect its TNF-alpha suppression by this mechanism. These findings indicate that IL-10 regulates production of pro-inflammatory cytokines by distinct mechanisms in different cells and tissues. Our study thus adds to the appreciation of the complex cytokine regulation of the immune system.