Atrial fibrillation and non-ischaemic cardiomyopathy in the peripartum period.

A 31-year-old primiparous woman with a history of bigeminy as a teenager developed atrial fibrillation with rapid ventricular response during elective caesarean section. Initial postoperative medical management was undertaken on the maternal high dependency unit and involved the administration of beta-blockers and digoxin. On postoperative day 1 the patient was transferred to the coronary care unit where she subsequently required synchronised direct current cardioversion to restore sinus rhythm. The patient remained on the coronary care unit for 5 days before discharge. Magnetic resonance imaging undertaken 6 weeks postpartum showed non-ischaemic cardiomyopathy. In this report, we discuss tachycardia-induced and peripartum cardiomyopathies, along with their potential underlying pathologies, incidence and associated morbidity. We describe potential pharmacological therapies including beta-blockers and angiotensin-converting enzyme inhibitors, as well as the implications of such medications for breastfeeding mothers. Patients presenting with palpitations in the antenatal period should receive prompt investigation including electrocardiography with ambulatory monitoring considered for those with persistent symptoms. Anyone with a proven cardiac arrhythmia should undergo echocardiography. This report illustrates the importance of the investigation of the symptoms of arrhythmia during pregnancy and emphasises the role of multidisciplinary working in the management of obstetric patients with complex medical comorbidity.

Changes in health-related quality of life after discharge from an intensive care unit: a systematic review.

Quality of life after critical illness is becoming increasingly important as survival improves. Various measures have been used to study the quality of life of patients discharged from intensive care. We systematically reviewed validated measures of quality of life and their results. We searched PubMed, CENTRAL, CINAHL, Web of Science and Open Grey for studies of quality of life, measured after discharge from intensive care. We categorised studied populations as: general; restricted to level-3 care or critical care beyond 5 days; and septic patients. We included quality of life measured at any time after hospital discharge. We identified 48 studies. Thirty-one studies used the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and 19 used the EuroQol-5D (EQ-5D); eight used both and nine used alternative validated measures. Follow-up rates ranged from 26-100%. Quality of life after critical care was worse than for age- and sex-matched populations. Quality of life improved for one year after hospital discharge. The aspects of life that improved most were physical function, physical role, vitality and social function. However, these domains were also the least likely to recover to population norms as they were more profoundly affected by critical illness.

Impact of the type of centre on management of AF patients: surprising evidence for differences in antithrombotic therapy decisions.

Atrial fibrillation (AF) patients may receive treatment from specialists or from general medicine physicians representing different levels of care within a structured health care system. This "choice" is influenced by patient flow within a health care system, patient preference, and individual access to health care resources. We analysed how the postgraduate training and work environment of treating physicians affects management decisions in AF patients. Patient characteristics and treatment decisions were analysed at the time of enrolment into the registry of the German Atrial Fibrillation NETwork (AFNET). A total of 9,577 patients were enrolled from 2004 to 2006 in 191 German centres that belonged to the following four levels of care: 13 tertiary care centres (TCC) enrolled 3,795 patients (39.6%), 58 district hospitals (DH) enrolled 2,339 patients (24.4%), 62 office-based cardiologists (OC) enrolled 2,640 patients (27.6%), and 58 general practitioners or internists (GP) enrolled 803 patients (8.4%). Patients with new-onset AF were often treated in DH. TCC treated younger patients who more often presented with paroxysmal AF. Older patients and patients in permanent AF more often received outpatient care. Consistent with recommendations, younger patients and patients with non-permanent AF received rhythm control therapy more often. In addition, the type of centre affected the decision for rhythm control. Stroke risk was similar between centre types (mean CHADS2 scores 1.6 -1.9). TCC (68.8%) and OC (73.6%) administered adequate antithrombotic therapy more often than DH (55.1%) or GP (52.0%, p<0.001 between groups). Upon multivariate analysis, enrolment by TCC or OC was associated with a 1.60 (1.20-2.12, p=0.001) fold chance for adequate antithrombotic treatment. This difference between centre types was consistent irrespective of the type of stroke risk estimation (ESC 2001 guidelines, CHADS2 score), and also consistent when the recently suggested CHA2DS2-VASc score was used to estimate stroke risk. In conclusion, management decisions in AF are influenced by the education and clinical background of treating physicians in Germany. Inpatients receive more rhythm control therapy. Adequate antithrombotic therapy is more often administered in specialist (cardiologist) centres.

[Registry and studies of the German Competence Network on Atrial Fibrillation (AFNET)]. / Register und Studien des Deutschen Kompetenznetzes Vorhofflimmern (AFNET).

The German Competence Network on Atrial Fibrillation (AFNET) is a national interdisciplinary research network funded by the Federal Ministry of Education and Research (BMBF). AFNET was initiated in 2003 and aims at improving treatment of atrial fibrillation (AF), the most frequent sustained cardiac arrhythmia. AFNET has established a nationwide patient registry on diagnostics, therapy, course and complications of AF in Germany. The data analyzed to date demonstrate that patients with AF are likely to have multiple co-morbidities, such as hypertension, valvular heart disease, coronary artery disease, diabetes mellitus and advanced age. Oral anticoagulation is provided to the majority of patients in accordance with the recommendations given by guidelines. Further areas of research deal with the optimal duration of antiarrhythmic therapy following electrical cardioversion of atrial fibrillation and the value of strategies to prevent arrhythmogenic changes, such as fibrosis in the atria, for prevention of further episodes of atrial fibrillation. Additional registry projects were established for patients with catheter-based interventional therapy of atrial fibrillation and surgical ablation to define success, complications and long term results of these recently developed procedures more clearly. Data and insights gathered from these projects were used to further develop standards of care in two international conferences.

Effect of cellulose wastes upon the growth of Phragmites australis.

Growth responses of Phragmites australis (Cav.) Trin. Ex Steud, (reed grass), a helophyte species, were examined under in vitro and greenhouse conditions in the presence of various residues from a Kraft pulp mill. Plant tolerance to solid residues (ashes, dregs, flyashes, grits, primary sludge, and brown stock rejects) was tested in vitro. Solid residues were added separately up to 30% (w/v), as well a liquid residue up to 30% (v/v), to a Murashige and Skoog (1962) sucrose-free nutrient media with (5 mg l(-1)) 6-benzylaminopurine. After 2 mo in vitro, plantlets developed well in the presence of up to 10% solid or liquid wastes, but higher concentrations of either limited growth. This effect was mainly attributed to the plant's uptake and accumulation of various elements such as sodium, iron, copper, manganese, and boron, which are common to these waste types, thus showing an efficient phytoremediation potential. When added to MS media, the concentration of these elements generally decreased in the residual media after 2 mo of culture: the initial sodium, iron, and copper content in the growth media was reduced ca. 10-fold detected; a 5-fold reduction occurred for manganese and boron. In experiments under greenhouse conditions with in vitro propagated plantlets potted in mixtures of a commercial organic soil and residues, significant differences in plant development (plant size and fresh weight increase) were observed in the presence of ashes mixed at levels of 20% and 30%, compared to the control in organic soil. For other solid wastes, plant growth was inhibited as the concentration of each waste increased, causing chlorosis and/or plant necrosis.

Degradation of 2,4,6-trinitrotoluene by selected helophytes.

Four emergent plants (helophytes, synonyms emersion macrophytes, marsh plants, etc.) Phragmites australis, Juncus glaucus, Carex gracillis and Typha latifolia were successfully used for degradation of TNT (2,4,6-trinitrotoluene) under in vitro conditions. The plants took up and transformed more than 90% of TNT from the medium within ten days of cultivation. The most efficient species was Ph. australis which took up 98% of TNT within ten days. The first stable degradation products 4-amino-2,6-dinitrotoluene (4-ADNT) and 2-amino-4,6-dinitrotoluene (2-ADNT) were identified and analysed during the cultivation period. [14C] TNT was used for the detection of TNT degradation products and their compartmentalization in plant tissues after two weeks of cultivation. Forty one percent of 14C was detected as insoluble or bound in cell structures: 34% in roots and 8% in the aerial parts. These results open the perspective of using the above-mentioned plants for the remediation of TNT contaminated waters.

Recipient MHC class II expression is required to achieve long-term survival of murine cardiac allografts after costimulatory blockade.

To study the role of the direct and indirect pathways in achieving tolerance, we used genetically altered mouse strains in two ways: 1) MHC class II-deficient mice were used as donors of skin and cardiac grafts to eliminate the direct CD4(+) T cell response, and 2) B6 II(-)4(+) mice, which are MHC class II-deficient mice expressing an MHC class II transgene only on thymic epithelium, were used as recipients of normal grafts. These mice cannot mount an indirect response. Eliminating the indirect pathway actually made it more difficult to achieve prolonged allograft survival when we used costimulatory blockade than when both pathways were available. Costimulatory blockade was ineffective even when CD4(+) T cells from normal animals were transferred into recipients that lacked MHC class II molecules. These results suggest that an active CD4(+) response through the indirect pathway is necessary for costimulatory blockade to be effective in prolonging allograft survival.

Early reinitiation of atrial fibrillation following external electrical cardioversion in amiodarone-treated patients.

UNLABELLED: Early reinitiation of atrial fibrillation (ERAF) following external or internal electrical cardioversion is one of the factors determining unsuccessful electrical cardioversion. Prevention of ERAF has not been studied systematically in patients on amiodarone therapy. METHODS AND RESULTS: 22 patients had ERAF within 1 min after external electrical cardioversion of atrial fibrillation. 11 patients were on amiodarone therapy and 11 patients had no antiarrhythmic medication. The effect of atropine, post-shock atrial pacing and intravenous ajmaline on ERAF was consecutively tested in these patients. Administration of atropine before repeated defibrillation or post-shock atrial pacing prevented ERAF in 9 of the 11 patients (82%) on amiodarone therapy but in only 3 of 11 patients (27%) without amiodarone (p<0.05). In the remaining patients, intravenous ajmaline was effective in the suppression of ERAF in 5 patients without amiodarone and in 1 patient with amiodarone. The PP interval preceding the atrial premature beat reinitiating atrial fibrillation was nonsignificantly longer in amiodarone-treated patients (1127+/-419 ms) in comparison to patients without amiodarone (896+/-271ms). 27% of patients without amiodarone at the time of electrical cardioversion and 55% of patients with amiodarone remained in sinus rhythm during the follow-up of 29+/-14 and 30+/-14 months, respectively. CONCLUSIONS: ERAF in patients on amiodarone can be treated by atropine or atrial pacing to prevent bradycardia-dependent ERAF. ERAF in amiodarone-treated patients does not apparently predict late recurrence of atrial fibrillation on continued amiodarone therapy.

NFATc1 and NFATc2 together control both T and B cell activation and differentiation.

NFAT transcription factors play critical roles in gene transcription during immune responses. To investigate further the two most prominent NFAT family members, NFATc1 and NFATc2, we generated mice bearing lymphoid systems devoid of both. Doubly deficient T cells displayed cell surface markers of activation yet were significantly deficient in the development of multiple effector functions, including Th cytokine production, surface effector molecule expression, and cytolytic activity. Nevertheless, doubly deficient B cells were hyperactivated, as evidenced by extremely elevated serum IgG1 and IgE, as well as plasma cell expansion and infiltration of end organs. Thus, in T cells, NFATc1 and NFATc2 are dispensable for inflammatory reactivity but are required for effector differentiation, while in B cells, NFATs regulate both normal homeostasis and differentiation.

Catheter ablation of atrial flutter due to amiodarone therapy for paroxysmal atrial fibrillation.

AIMS: Antiarrhythmic drug treatment for atrial fibrillation can cause atrial flutter-like arrhythmias. The aim of this study was to clarify the effect of catheter ablation of the tricuspid annulus-vena cava inferior isthmus on amiodarone-induced atrial flutter and to determine the incidence of atrial fibrillation after catheter ablation of amiodarone-induced atrial flutter in comparison to regular typical flutter. METHODS AND RESULTS: Among 92 consecutive patients with typical atrial flutter who underwent isthmus ablation 28 patients had atrial flutter without a history of previous atrial fibrillation (group I), 10 patients had atrial flutter following the initiation of amiodarone therapy for paroxysmal atrial fibrillation (group II) and 54 patients had atrial flutter and atrial fibrillation (group III). Atrial cycle length during atrial flutter in amiodarone-treated patients (group II) (277+/-24 ms) was significantly longer as compared to the cycle length of atrial flutter in group I (247+/-33 ms) and group III patients (235+/-28 ms). The rate of successful transient entrainment and overdrive stimulation to sinus rhythm was not different between patients with (60%) or without amiodarone therapy (group I: 71%, group III: 53%). Successful isthmus ablation with bidirectional conduction block eliminating right atrial flutter was achieved in 90% of amiodarone-treated patients and 93% of patients without amiodarone therapy. In the amiodarone-treated patient group atrial conduction times during pacing in sinus rhythm were significantly prolonged by 20-30% before and after ablation in all regions of the reentrant circuit. During a mean follow-up of 8+/-3 months post-ablation, atrial fibrillation recurred in two of 10 patients on continued amiodarone therapy after successful isthmus ablation. Thus, successful catheter ablation of atrial flutter due to amiodarone therapy was associated with a markedly lower recurrence rate of paroxysmal atrial fibrillation (20%) as compared to patients with atrial flutter plus preexisting paroxysmal atrial fibrillation (76%) and was similar to the outcome of patients with successful atrial flutter ablation without preexisting atrial fibrillation (25%). CONCLUSION: These data suggest that isthmus ablation with bidirectional block and continuation of amiodarone therapy is an effective therapy for the treatment of atrial flutter due to amiodarone therapy for paroxysmal atrial fibrillation.

Sequential involvement of NFAT and Egr transcription factors in FasL regulation.

The critical function of NFAT proteins in maintaining lymphoid homeostasis was revealed in mice lacking both NFATp and NFAT4 (DKO). DKO mice exhibit increased lymphoproliferation, decreased activation-induced cell death, and impaired induction of FasL. The transcription factors Egr2 and Egr3 are potent activators of FasL expression. Here we find that Egr2 and Egr3 are NFAT target genes. Activation of FasL occurs via the NFAT-dependent induction of Egr3, as demonstrated by the ability of exogenously provided NFATp to restore Egr-dependent FasL promoter activity in DKO lymph node cells. Further, Egr3 expression is enriched in Th1 cells, suggesting a molecular basis for the known preferential expression of FasL in the Th1 versus Th2 subset.

Co-localization of corticotropin-releasing hormone with glutamate decarboxylase and calcium-binding proteins in infant rat neocortical interneurons.

Corticotropin releasing hormone (CRH) has been localized to interneurons of the mammalian cerebral cortex, but these neurons have not been fully characterized. The present study determined the extent of co-localization of CRH with glutamate decarboxylase (GAD) and calcium-binding proteins in the infant rat neocortex using immunocytochemistry. CRH-immunoreactive (ir) neurons were classified into two major groups. The first group was larger and consisted of densely CRH-immunostained small bipolar cells, predominantly localized to layers II and III. The second group of CRH-ir cells was lightly labeled and included multipolar neurons mainly found in deep cortical layers. Co-localization studies indicated that the vast majority of CRH-ir neurons, including both bipolar and multipolar types, was co-immunolabeled for GAD-65 and GAD-67. Most multipolar, but only some bipolar, CRH-ir neurons also contained parvalbumin, while CRH-ir neurons rarely contained calbindin or calretinin. These results indicate that virtually all CRH-ir neurons in the rat cerebral cortex are GABAergic. Furthermore, since parvalbumin is expressed by cortical basket and chandelier cells, the co-localization of CRH and parvalbumin suggests that some cortical CRH-ir neurons may belong to these two cell types.

Corticotropin releasing hormone antagonist does not prevent adrenalectomy-induced apoptosis in the dentate gyrus of the rat hippocampus.

Adrenalectomy in the mature rat leads to death of granule cells in the dentate gyrus of the hippocampal formation. The mechanisms underlying this cell death have not been fully clarified: It has been considered that the granule cells require adrenal steroids for their survival, since corticosterone replacement prevents their death. However, adrenalectomy-induced loss of negative feedback also increases levels of corticotropin releasing hormone (CRH) in several limbic brain regions. CRH is known to induce neuronal death in hippocampal regions rich in CRH receptors. This study tested the hypothesis that adrenalectomy-induced granule cell death is mediated via the enhanced activation of CRH receptors. The extent of granule cell degeneration was compared among 4 groups of young adult male rats: Sham-adrenalectomy controls, adrenalectomized rats, adrenalectomized rats infused with a CRH antagonist from the onset of steroid deprivation to the time of sacrifice, and adrenalectomized rats infused with vehicle only. (9-41)-alpha-helical CRH was administered using an osmotic pump into the cerebral ventricles. Adrenalectomy led to robust granule cell degeneration, which was maximal in the suprapyramidal blade of the dentate gyrus. Infusion of the CRH antagonist in doses shown to block CRH actions on limbic neurons did not decrease the number of degenerating granule cells compared with the untreated or vehicle-infused adrenalectomized groups. Therefore, blocking the actions of CRH does not prevent adrenalectomy-induced granule cell death, consistent with a direct effect of corticoids on the survival of these neurons.

Febrile seizures: an appropriate-aged model suitable for long-term studies.

Seizures induced by fever are the most prevalent age-specific seizures in infants and young children. Whether they result in long-term sequelae such as neuronal loss and temporal lobe epilepsy is controversial. Prospective studies of human febrile seizures have found no adverse effects on the developing brain. However, adults with temporal lobe epilepsy and associated limbic cell loss frequently have a history of prolonged febrile seizures in early life. These critical issues may be resolved using appropriate animal models. Published models of hyperthermic seizures have used 'adolescent' and older rats, have yielded a low percentage of animals with actual seizures, or have suffered from a high mortality, rendering them unsuitable for long-term studies. This article describes the establishment of a model of febrile seizures using the infant rat. Hyperthermia was induced by a regulated stream of mildly heated air, and the seizures were determined by both behavioral and electroencephalographic (EEG) criteria. Stereotyped seizures were generated in 93.6% of 10-11-day-old rats. EEG correlates of these seizures were not evident in cortical recordings, but were clearly present in depth recordings from the amygdala and hippocampus. Prolonged febrile seizures could be induced without burns, yielding a low mortality (11%) and long-term survival. In summary, in infant rat paradigm of EEG-confirmed, hyperthermia-induced seizures which is suitable for long-term studies is described. This model should be highly valuable for studying the mechanisms and sequelae of febrile seizures.

[Left ventricular catheter ablation of the AV conduction system with radiofrequency electric current]. / Linksventrikuläre Katheterablation des AV-Uberleitungssystems mit Radiofrequenzstrom.

We report on a 32-year-old female patient with a history of recurrent atrial fibrillation and rapid ventricular response (up to 240 beats/min) resistant to multiple drug therapy. In this patient, we successfully performed a radiofrequency catheter ablation of the atrioventricular (AV) junction from the left ventricle, after radiofrequency energy application in His-position above the tricuspid valve was unsuccessful. This technique offers an-alternative treatment in patients in whom the conventional right-sided catheter ablation of the AV junction proves ineffective.