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Relationship between cardiac troponin I (cTnI) release during cardiac operations and myocardial cell death
JF Vazquez-Jimenez, Ma Qing, B Klosterhalfen, O Liakopoulos, G von Bernuth, BJ Messmer, M-C Seghaye
Critical Care , 2000, DOI: 10.1186/cc722
Abstract: Eighteen young pigs were operated on with standardized cardiopulmonary bypass (CPB). Release of cTnI in the cardiac lymph (CL), coronary sinus (CS), and arterial blood (A) was related to postoperative myocardial cell death by both necrosis and apoptosis. Apoptotic cells were detected by a TUNEL detection kit. Necrotic cells were counted by light microscopy.In all animals, cTnI was significantly released and reached peak values observed simultaneously in A (cTnI, 20.1 ± 2.6 ng/ml) (mean ± SEM), CS (19.5 ± 3.2 ng/ml) and CL (5202 ± 2500 ng/ml). Percentage of total myocardial cell death was 3.1 ± 0.5%, including 1.2 ± 0.35% necrosis and 1.9 ± 0.5% apoptosis. cTnI release during and after CPB did not correlate with the degree of myocardial apoptosis or necrosis.Cardiac operations with CPB are related to myocardial cell damage including myocardial cell death due to both necrosis and apoptosis. As the loss of cTnI is not related to the amount of cell death, our results suggest that increased cardiac myocyte membrane permeability more than cell death is responsible for intraoperative and postoperative cTnI release.
Transfrontera Crimes: Representations of the Juárez Femicides in Recent Fictional and Non-Fictional Accounts
Marietta Messmer
American Studies Journal , 2012,
Abstract: In her article, Marrietta Messmer discusses the representation of the Juárez femicides and their traumatizing effects on the Juárez/El Paso community in four recently published accounts: Teresa Rodriguez's journalistic account The Daughters of Juarez (2007), the documentary Se orita Extraviada (2001) directed by Lourdes Portillo, the feature film Bordertown (2006), directed by Gregory Nava, and Alicia Gaspar de Alba's mystery novel Desert Blood: The Juárez Murders (2005). More specifically, she analyzes the degree to which these sources regard the femicides not merely as a Mexican problem but as a structural and highly significant transborder issue that has its roots in the region's current political and economic developments, as well as its pervasive social and cultural changes.
Temperature Isotropization in Solar Flare Plasmas due to the Electron Firehose Instability
Peter Messmer
Physics , 2001, DOI: 10.1051/0004-6361:20011583
Abstract: The isotropization process of a collisionless plasma with an electron temperature anisotropy along an external magnetic field ($T_\| ^e\gg T_\perp^e$, $\|$ and $\perp$ with respect to the background magnetic field) and isotropic protons is investigated using a particle-in-cell(PIC) code. Restricting wave growth mainly parallel to the external magnetic field, the isotropization mechanism is identified to be the Electron Firehose Instability (EFI). The free energy in the electrons is first transformed into left-hand circularly polarized transverse low-frequency waves by a non-resonant interaction. Fast electrons can then be scattered towards higher perpendicular velocities by gyroresonance, leading finally to a complete isotropization of the velocity distribution. During this phase of the instability, Langmuir waves are generated which may lead to the emission of radio waves. A large fraction of the protons is resonant with the left-hand polarized electromagnetic waves, creating a proton temperature anisotropy $T_\|^p < T_\perp^p$. The parameters of the simulated plasma are chosen compatible to solar flare conditions. The results indicate the significance of this mechanism in the particle acceleration context: The EFI limits the anisotropy of the electron velocity distribution, and thus provides the necessary condition for further acceleration. It enhances the pitch-angle of the electrons and heats the ions.
The effect of temperature during extracorporeal circulation on ultrastructure of cardiomyocytes
R Chakupurakal, B Hermanns, JF Vazquez-Jiminez, Ma Qing, S Lücking, BJ Messmer, G von Bernuth, M-C Seghaye
Critical Care , 2001, DOI: 10.1186/cc1001
Abstract: Fifteen pigs were randomly assigned to one of three temperature groups (37, 28 and 20°C) during ECC (n = 5 each). ECC time was 120 min and myocardial ischaemia time was 60 min. Cardioplegia was achieved by injecting a crystalloid solution (4°C cold Bretschneider solution, 30 ml/kg) into the aortic root. Flow index was set at 2.7 l/m2 per min. Six hours after ECC, myocardial samples were taken from the left ventricle for ultrastructural examination by electron microscopy.All animals showed intact contractile apparatus, with normal texture of the myofibrils and normal configuration of the Z-bands. Quantitative and structural changes of mitochondria were frequent. Animals from the 37°C group showed marked interstitial oedema and dehiscence of the cytoplasmatic membrane with ruptures, whereas lesser damage to the membrane was observed in the other two groups. The 28°C group showed the least pronounced ultrastructural changes.These results show that cardiac operations with ECC are associated with ultrastructural lesions of the cardiomyocytes. In this experimental setup, these lesions were most pronounced under normothermic and least pronounced under moderate hypothermic ECC.
Effect of temperature on leukocyte activation during cardiopulmonary bypass (CPB) and postoperative organ damage
M Qing, M-C Seghaye, JF Vazquez-Jimenez, RG Grabitz, B Klosterhalfen, M Sigler, BJ Messmer, G von Bernuth
Critical Care , 1999, DOI: 10.1186/cc331
Abstract: 18 young pigs were randomly assigned to a T°- group during CPB: normothermia (T° 37°C; n = 6), mild hypothermia (T° 28°C; n = 6) and deep hypothermia (T° 20°C; n = 6). Leukocyte count and plasma levels of tumor necrosis factor (TNFα) were measured before, during and after CPB. At the end of the experimentation (6 h post-CPB), probes of heart, lungs, liver, kidney, and intestine were taken for histological examination.There was a significant fall of leukocyte count at induction of CPB, without any intergroup difference. During and at the end of CPB, leukocyte count was significantly higher in group 37°C as compared with the other groups. At a later stage after CPB, group 20°C showed significantly higher leukocyte count than group 28°C and group 37°C, respectively. The course of neutrophils was similar.TNF-α was not released in group 28°C neither during nor after CPB. By contrast, there was a significant production of TNF-α in groups 37°C and 20°C, the circulating levels being significantly higher in group 37°C. Histological examination showed that the most important tissue damage in terms of interstitial edema and leukostasis in heart, lung, liver, kidney, and small intestine was seen in group 37°C followed by group 20°C while the least important damage was present in group 28°C.CPB-induced postoperative organ damage, probably related to leukocyte activation and TNF-α production, is highest in pigs operated on in normothermia and lowest in those operated on in mild hypothermia.
Influences of pre-, peri- and postoperative risk factors in neonatal cardiac surgery on neurodevelopmental status in preschool-age children
HH H?vels-Gürich, M-C Seghaye, M Sigler, A Bartl, F Kotlarek, J Neuser, BJ Messmer, G von Bernuth
Critical Care , 2000, DOI: 10.1186/cc676
Abstract: Thirty-three unselected children operated on as neonates with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass were examined at an age of 3.0–4.6 years [3.6 ± 0.5 (mean ± standard deviation)]. The control group for developmental outcome consisted of 32 age-matched healthy children, who were 3.0–4.8 years [3.8 ± 0.6 (mean ± standard deviation)] of age. Evaluation of socioeconomic status and a standardised test comprising all areas of child development (Vienna developmental test), including scores of motor and cognitive functions, perception, language, learning and behaviour, were carried out in patients and controls, and clinical neurological status was assessed in patients. Results of patients were related to those of the control group and to pre-, peri-, and postoperative cerebral risk factors of the control group and to pre-, peri-, and postoperative cerebral risk factors as described in the context.Neurological impairment was more frequent (6.1%) than in the normal population. Compared with published norms, complete developmental score and the subtests for motor function, visual perception and visual motor integration, learning and memory, cognitive function, language, and socioemotional functions were not different. Compared with the control group, complete developmental score, cognitive score and language were reduced (P < 0.01), but socioeconomic status was significantly lower in the patient group (P = 0.0001). Motor function was weakly, but significantly inversely related to the duration of circulatory arrest (Pearson correlation coefficient -0.37; P = 0.049), but not to the duration of bypass. The other developmental parameters were not related to the duration of the support techniques. Serum levels of the biochemical marker neuron-specific enolase, although significantly elevated at the end of bypass (P = 0.0002) and 4 h after surgery (P = 0.0012) compared with preoperative values, were not correlated to developmental test re
Myocardial cell damage related to arterial switch operation in neonates with transposition of the great arteries
HH H?vels-Gürich, JF Vazquez-Jimenez, A Silvestri, K Schumacher, S Kreitz, J Duchateau, BJ Messmer, G von Bernuth, M-C Seghaye
Critical Care , 2001, DOI: 10.1186/cc1009
Abstract: Sixty-three neonates (age 2-28 [8.1 ± 4.6] days), who were operated on under combined deep hypothermic (15°C) circulatory arrest and low-flow cardiopulmonary bypass (CPB), were studied. Inclusion criteria were transposition of the great arteries with or without ventricular septal defect (VSD) that was suitable for arterial switch operation (VSD-; n = 53), and if necessary additional VSD closure (VSD+; n = 10). Patients were differentiated clinically into two groups by presence or absence of MD within 24 h after surgery. MD was defined as myocardial ischaemia after coronary reperfusion and/or myocardial hypocontractility as assessed by echocardiography. MD was related to clinical outcome parameters and to perioperative release of cardiac troponin-T (cTnT) and production of interleukin-6 and interleukin-8.MD was observed in 11 patients (17.5%). Two patients died early after surgery from myocardial infarction, and two died late after surgery (6.3%). CPB and cross-clamping, but not deep hypothermic circulatory arrest times, were correlated with MD; MD was more frequent in the VSD+ than in the VSD- group because of longer support times. Coronary status and age at surgery were not related to MD. Patients with MD had more frequently impaired cardiac, respiratory and renal functions. cTnT, interleukin-6 and interleukin-8 were significantly elevated at the end of CPB, and 4 and 24 h after surgery, as compared with preoperative values in both groups. Postoperative cTnT, interleukin-6 and interleukin-8 concentrations were significantly higher in MD patients than in the others. Multivariable analysis of independent risk factors for MD revealed interleukin-6 4 h after surgery to be significant (P = 0.04; odds ratio 1.24 [95% confidence interval 1.01-1.52] per 10 pg/ml). The cutoff point for prediction of MD was set at 500 pg/ml (specificity 95.4%, sensitivity 72.7%).Cardiac operations in neonates induce the production of the proinflammatory cytokines interelukin-6 and interleuki
Neurodevelopmental outcome related to cerebral risk factors in children after neonatal arterial switch operation
HH H?vels-Gürich, MC Seghaye, M Sigler, A Bartl, F Kotlarek, J Neuser, BJ Messmer, G von Bernuth
Critical Care , 1999, DOI: 10.1186/cc330
Abstract: Protracted birth (PB), perinatal asphyxia (PA), intraventricular cerebral haemorrhage (IVH) evaluated by pre/peri/postoperative cranial ultrasound, clinical seizures (CS) and high levels of the neuron-specific enolase (NSE) prior to as well as immediately after and 4 and 24 h after CPB in 25 neonates (mean age 7 days) were defined as cerebral risk factors. Correlation analyses (Fisher's Exact Test, Pearson Coefficient) were performed to the results of formalized clinical neurological (CNS) and complete developmental score (CDS) including 7 subtests (Vienna developmental test, standard values defined normal 100 ± 10, mean ± SD) at mean age 3.7 ± 0.5 years.PB was found in 16%, PA 0%, IVH 48%, residual IVH at discharge 24%, CS prior to surgery 16%, CS > 24 h after CPB 12%. NSE, elevated prior to surgery (11.3 ± 4.5 ng/ml, mean ± SD), increased to peak values 4 h after CPB (17.3 ± 6.0) and individual peak values within 24 h after CPB (19.9-7.0). CNS was normal in 84%, 16% had strabism. CDS was normal in 88% (100 ± 8), motor score 96% (99 ± 6), visual perception 88% (100 ± 9), learning and memory 96% (102 ± 7), cognitive score 100% (101 ± 8), language 100% (99 ± 5), socioemotional score 100% (103 ± 7). Developmental scores did not differ significantly from normal children. None of the considered risk factors had significant influence on any outcome parameter (P > 0.1 in all).In our study, neurodevelopmental outcome was not found dependent on cerebral risk factors as elevated NSE indicative of neuronal cell damage, intraventricular haemorrhage, seizures or pre-/perinatal asphyxia. Rare incidence of reduced test results might have masked significant correlations.
Is gastric malperfusion and endotoxemia one motor of the systemic inflammatory response syndrome following cardiac surgery?
JP Groetzner, T Graeter, I Lauermann, L Demircan, S Jockenh?vel, JF Vazquez-Jimenez, BJ Messmer, HJ HJ Sch?fers
Critical Care , 1999, DOI: 10.1186/cc318
Abstract: We evaluated one group with low risk for developing SIRS (Group1: coronary artery bypass grafting without CHF) and a high risk group (Group 2: mitral valve surgery with CHF) with 10 patients each for clinical and laboratory signs of SIRS as defined by BONE. Intramucosal gastric pH, endotoxin was detected using a tonometric gastric tube (Baxter Inc.), TNFα and interleukin 6 (IL6) were measured with an ELISA at nine different times pre-, intra- and postoperatively.Groups were similar with regards to age and sex. Cardiac Index was lower in Group 2 (1.7 ± 0.3 l/min/cm3) than in Group 1 (2.8 ± 0.5 l/min/cm3; P < 0.05). In Group 2 the aortic cross clamping time was longer (Group 1: 59.6 ± 15.2 min, Group 2: 42.7 ± 19.4 min) and norepinephrine requirements for maintenance of vascular resistance were higher (8.2 ± 12.6 mg) than in Group 1 (1.7 ± 2 mg; P < 0.05).At the end of CPB gastric pH dropped to 7.33 ± 0.34 in Group 2 whereas the other group remained stable between 7.47 and 7.5 (P < 0.05). Endotoxin levels were significantly elevated and significantly higher in Group 2 (37.2 ± 3.2 pg/ml) than in Group 1 (20.6 ± 3.7 pg/ml; P < 0.05) after aortic cross clamp was opened. In Group 1 only in 1 of 3 patients (33%) with gastric acidosis endotoxin was detected, whereas in Group 2 8/9 patients (88%) endotoxemia occurred.TNFα was elevated in both groups during CPB and significantly higher in Group 2 at aortic declamping (Group 1: 19.6 ± 2.9 pg/ml; Group 2: 39 ± 4.8 pg/ml; P < 0.05) and after protamin application (Group 1: 27.3 ± 4.2 pg/ml; Group 2: 62.8 ± 8.1 pg/ml; P < 0.05). After protamin application IL6 raised postoperatively and was significantly higher in Group 2 (653 ± 75 pg/ml) than in Group 1 (547 ± 439 pg/ml). SIRS occurred more often in Group 2 (9/10) than in Group 1 (6/10) postoperatively. All patients with detected endotoxemia developed SIRS (13/13). (see Figure).SIRS is more common in patients with CHF undergoing CPB than in others. This seems to be related to a dr
Treatment of solid tumors with immunotoxins
Davorka Messmer, Thomas J Kipps
Breast Cancer Research , 2005, DOI: 10.1186/bcr1284
Abstract: In this issue of Breast Cancer Research, von Minckwitz and colleagues [1] report the results of phase I study conducted in patients with advanced cancer using ScFv(FRP5)-ETA, a recombinant, single chain (sc) antibody toxin with binding specificity for HER2 [2,3] linked to Pseudomonas exotoxin A (ETA). Although significant clinical responses were not observed, ScFv(FRP5)-ETA appeared to be well tolerated at dose levels that may prove clinically active. As such, ScFv(FRP5)-ETA joins a growing list of promising new agents in targeted therapy for solid tumors.The notion of targeted tumor killing is has been around since early in the past century. In 1906, Ehrlich [4] introduced the concept of targeting cancer cells with a 'magic bullet', consisting of tissue-specific carriers that would deliver toxic agents to neoplastic tissue. The advent of mAbs made it possible to generate virtually unlimited amounts of antibody specific for antigens that are differentially expressed by tumor cells versus their normal cell counterparts. Although examples of truly tumor-specific antigens are rare, it is often possible to find tumor-associated antigens that are restricted in their tissue distribution or that are expressed at aberrantly high levels by tumor cells. A prime example of the latter is HER2/neu, a surface protein that is over-expressed by many types of cancers, in particular adenocarcinoma of the breast [5-7]. As such, HER2/neu is an attractive target for antibody-directed therapies.In fact, the first mAb approved for the use in solid tumor therapy was Herceptin, a humanized mAb specific for HER2. It is currently used in the treatment of breast cancer as monotherapy or in combination with chemotherapeutic agents. Although remarkable objective responses were observed, only a fraction of patients experienced a complete response and/or a long-lasting response with this mAb [8-11]. In addition, side effects such as cardiac dysfunction have been observed, the incidence and severit
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