Alteration of Endothelin 1, MCP-1 and Chromogranin A in patients with atrial fibrillation undergoing pulmonary vein isolation.

BACKGROUND: The relation between arrhythmias and stress is known. The aim of our current study was to elucidate whether plasma levels of previously described stress parameters are altered in highly symptomatic patients with atrial fibrillation (AF) per se and in patients undergoing ablation therapy by pulmonary vein isolation (PVI). METHODS: 96 patients with AF undergoing PVI were recruited. Plasma levels of Endothelin-1 (ET-1), MCP-1 and Chromogranin-A (CGA) were measured before and three months after ablation completed with clinical follow-up with respect to AF recurrence. Additionally, we examined 40 healthy age- and sex-matched volunteers as a reference. RESULTS: Symptomatic AF patients showed increased levels of ET-1 compared to healthy controls (2.62pg/ml vs. 1.57pg/ml; p<0.01). Baseline levels of ET-1 were higher in patients presenting with AF after PVI (2.96pg/ml vs. 2.57pg/ml;p = 0.02). The temporal comparison revealed decreased ET-1 levels in patients without (2.57pg/ml vs. 2.33pg/ml; p<0.01) and unchanged ET-1 levels in patients with AF after PVI. Baseline MCP-1 was increased in AF patients vs. controls (268pg/ml vs. 227 pg/ml; p = 0.03). Both groups, with and without AF after PVI, showed an increase of MCP-1 compared to baseline (268pg/ml vs. 349pg/ml;p<0.01; 281pg/ml vs. 355pg/ml;p = 0.03). CGA was lower in AF patients compared to healthy controls (13.8ng/ml vs. 25.6ng/ml;p<0.01). Over time patients without AF after PVI showed an increase of CGA (14.2ng/ml vs. 20.7ng/ml;p<0.01). No change was observed in patients with AF after PVI. CONCLUSION: Our study demonstrated dysregulated levels of ET-1, MCP-1 and CGA in symptomatic AF patients. We could demonstrate an association between ET-1 to presence or absence of AF. Furthermore, we could show that a decrease of ET-1 as well as an increase of CGA after PVI, representing a trend towards control cohort levels, were both associated with restoration of sinus rhythm. These results provide new insights into the role of stress-related biomarkers in AF and AF treatment by ablation therapy.

Diagnostic and prognostic value of miR-1 and miR-29b on adverse ventricular remodeling after acute myocardial infarction - The SITAGRAMI-miR analysis.

BACKGROUND: MicroRNAs (miRs) have shown to exert fibrotic and anti-fibrotic effects in preclinical models of acute myocardial infarction (AMI). The aim of this study was to evaluate miR-1, miR-21, miR-29b and miR-92a as circulating biomarkers for adverse ventricular remodeling (AVR) in post-AMI patients. METHODS: Plasma levels of miR-1, miR-21, miR-29b and miR-92a were measured in 44 patients of the SITAGRAMI trial population at day 4, day 9 and 6month after AMI and in 18 matched controls (CTL). MiR expression patterns were correlated with magnetic resonance imaging (MRI) parameters for AVR (absolute change (Δ) in infarct volume (IV), left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume (LVEDV) between day 4 and 6months after AMI) and a combined cardiovascular endpoint. RESULTS: Expression of miR-1, miR-21 and miR-29b but not miR-92a was increased in AMI vs. CTL cohort showing highest miR levels at d9. However, only miR-1 and miR-29b levels significantly correlated with ΔIV and showed a trend for correlation with ΔLVEF. Only miR-29b levels at day 9 correlated with ΔLVEDV at 6-month follow-up. There was no correlation of miR levels with an adverse outcome. CONCLUSION: Mir-1 and miR-29b plasma levels post-AMI correlate with IV changes. In addition, miR-29b levels are associated with changes of LVEDV over time. These results provide insights into the role of miRs as diagnostic AVR surrogate markers. Further large scale clinical trials will be needed to evaluate the real prognostic relevance of these miRs with respect to a clinical implication in the future.

Remote monitoring of implantable cardioverter-defibrillators. Problems and implications using a telemonitoring system.

The rising number of implantable devices has led to an increase in device-related workload, e.g., regular interrogation follow-up visits. Telemonitoring systems for implantable cardioverter-defibrillators (ICDs) seem to be a promising tool for reducing workload and costs, and they have the potential of optimizing patient care. However, issues such as practical functionality of ICD telemonitoring in daily routine may affect its broad implementation. The objective of this study was to evaluate potential problems during the implementation of a telemonitoring system, Medtronic CareLink™ (CL™) with respect to the installation and data transmission process. A total of 159 patients with ICDs who were equipped with the CL™ system were evaluated and followed up for 16 months regarding the success rate of the first data transmission via the telemonitoring system. In this cohort, a high rate of nontransmission of 23.9 % was observed after the 16-month follow-up. A detailed interview of these patients (no transmission) revealed that the main reasons for failed transmissions were due to the patients' loss of interest in the concept (approximately 50 %) as well as technical problems (approximately 25 %) with setting up the system. These results indicate that telemonitoring systems bear potential problems and that the evaluation of patient motivation and technical support options seems to play an important role in establishing the functionality of these systems.

[Molecular mechanisms of atrial fibrillation: potential role of microRNAs as new therapeutic targets and potential biomarkers]. / Molekulare Mechanismen von Vorhofflimmern: Potenzielle Rolle der microRNAs als neues therapeutisches Ziel und als möglicher Biomarker.

Atrial fibrillation represents the most common form of clinical arrhythmia in daily routine. However, current therapeutic options are still limited and a better understanding of the underlying molecular mechanisms is expected to contribute to the development of new therapeutic strategies. The scientific field of microRNA research has received a lot of attention in recent years, especially regarding cardiovascular research. This article gives a brief overview of the most recent developments in microRNA research in the field of atrial fibrillation and atrial remodelling processes. Furthermore, the clinical perspective of microRNAs as new therapeutic targets and as potential biomarkers is discussed.

["STUMP" (smooth muscle tumour of uncertain malignant potential), a tumour of the uterus in pregnancy--a diagnostic and therapeutic challenge]. / "STUMP" (smooth muscle tumor of uncertain malignant potential), ein Uterustumor in der Schwangerschaft, eine diagnostische und therapeutische Herausforderung.

We present the case of a preterm birth in the 27 (th) week of gestation, probably due to a chorionamnionitis, with the coincidental finding of a STUMP (smooth muscle tumour of uncertain malignant potential). The STUMP is a rare tumour entity characterised by smooth muscle cells which is difficult to classify by means of histology. The WHO classification of mesenchymal tumours allocates STUMP as an intermediate tumour between a benign leiomyoma and a malignant leiomyosarcoma. If histological criteria of malignancy are not fulfilled because the type of necrosis is in doubt or the interpretation of mitotic figures is ambiguous and the tumour cannot reliably be classified as a leiomyoma, it is classified as a STUMP. Compared to malignant leiomyosarcoma, STUMP has a superior prognosis, but the biological potential of the tumour remains unclear; lymphogenic and haematogenic dissemination seems possible even after a long period of time. STUMP represents a challenge in diagnosis and treatment recommendations. We present the first description of a case of STUMP during pregnancy, raising the question of whether the histological finding in tumours of the uterus during pregnancy are important.

Tubular atrophy, interstitial fibrosis, and inflammation in type 2 diabetic db/db mice. An accelerated model of advanced diabetic nephropathy.

OBJECTIVE: Advanced diabetic nephropathy (DN) is difficult to address experimentally in mice because available models of DN lack global glomerulosclerosis and major tubulointerstitial pathology. Accelerating the development of DN in mice would be desirable for feasible experimental validation of potential targets that mediate the progression to late stage DN. METHODS: 6 week old male db/db mice underwent uninephrectomy and the development of nephropathy was compared to wild-type mice and sham-operated db/db mice. RESULTS: Uninephrectomy at young age was associated with increased albuminuria and severe glomerulosclerosis in 37% of glomeruli at 24 weeks of age as compared to sham-operated db/db mice (8%). Uninephrectomy also increased the number of glomerular macrophages in db/db mice. The uninephrectomy-related acceleration of glomerular damage was associated with significant tubulointerstitial injury as indicated by an increase in indices of tubular cell damage, tubular dilatation, and expansion of interstitial volume. Uninephrectomy markedly increased the renal mRNA expression of Mcp-1/Ccl2, Tgf-beta, and collagen I. CONCLUSION: Early uninephrectomy can accelerate the development of advanced DN in db/db mice which may be instrumental in the design of interventional studies that intend to focus on the molecular pathology of the progression to late stage DN.

Primary antiphospholipid antibody syndrome and cardiac involvement in a child.

We report a case of polyvalvar disease and recurrent thrombosis in a 2-year-old boy due to primary antiphospholipid antibody syndrome. His diagnosis was delayed, and he was treated for other diagnoses, including culture-negative endocarditis. Primary antiphospholipid antibody syndrome is rarely discussed in the pediatric cardiology literature, and this case highlights the need for early diagnosis to prevent recurrent valve dysfunction and thrombosis.

Long-term safety and efficacy of low-fat diets in children and adolescents.

The safety and efficacy of low-fat diets in children and adolescents were evaluated through a systematic review of the current literature. Eight major studies were reviewed. The safety of the diets was judged by measures of growth and development and by meeting nutritional requirements. The efficacy of the diets was evaluated by their effect on the plasma levels of total cholesterol and low-density lipoprotein (LDL) cholesterol. All studies except 1 showed that children and adolescents exhibited normal growth and development while on a low-fat diet. In 3 of the studies, nutritional requirements for calcium, zinc, phosphorous and vitamin E were below the recommended daily intake. In each of the 5 studies in which efficacy was determined, a significant decrease in the levels of total or LDL cholesterol was observed. Low-fat diets are generally safe and efficacious when performed under medical supervision.

[Contraception in young girls. A survey conducted in the MFPF Family Planning Center, Strasbourg in 1985]. / Les jeunes filles et la contraception. Enquete realisee dans le centre de planification du MFPF a Strasbourg en 1985.

PIP: 513 adolescent females attending a family planning center administered by the French Movement for Family Planning in Strasburg completed anonymous questionnaires between December 1984-June 1985 to identify the sociological and clinical characteristics of the clinic users. About 80% were 16-19 years old. 314 came unaccompanied to the center, 149 came with a friend, and 25 came with their partner. It was the 1st consultation for 278 respondents. 126 had been coming for less than 1 year, 67 for 1-2 years, 31 for 2-3 years, and 11 for more than 3 years. 83% were students. 312 resided in Strasburg or its suburbs and 201 resided elsewhere. Anonymity was the principal reason why clients travelled long distances to attend the center. 372 knew of the center through friends or sisters, 44 through the media, 40 through school, 11 through parents, and 7 through a doctor. 121 reported that their parents knew they used contraception and 382 that they did not know. 318 preferred a woman doctor for a contraceptive consultation, 180 did not care, and 6 preferred a man. Over half had their 1st menstrual period between the ages of 12 and 13. 172 were virgins at the time of their 1st consultation. The age of 1st intercourse was 14-17 years old for 81% and 15 or 16 for 48%. 155 used no contraception before visiting the center, 114 used withdrawal, 73 used condoms, 20 used spermicides, 38 used oral contraceptives (OCs) prescribed elsewhere, and 9 used other methods. 66% of prescriptions were for standard dosed pills because less than 2 years had passed since menarche, the cycles were irregular, or the client had acne or feared forgetting a pill. At the 3-month follow-up the prescription was changed to a lowdose pill in 43 cases because of side effects, while a low dose pill was changed to standard dose in 20 cases because of acne or forgetting. 24 girls came for a morning after pill and 31 for a pregnancy test. 9 reported they had already had abortions. 163 did not smoke, 152 smoked less than 1/2 pack daily, 150 smoked 1/2-1 pack, and 43 smoked more than 1 pack. 434 had a normal weight for their height and 56 were obese. 33% did not return after their 1st consulatation. Frank hyperlipidemia was rare among the clients tested.^ieng

[Young girls and contraception. A survey conducted in the MFPF family planning center, Strasbourg, in 1985]. / Les jeunes filles et la contraception. Enquete realisee dans le centre de planification du MFPF a Strasbourg en 1985.

The results of a survey on contraception among 513 adolescent women attending a family planning clinic in Strasbourg, France, in 1985 are presented. "Eighty percent of them were attending school. In over half the cases, this was their first consultation for contraceptive advice. 33% of the subjects did not return after this initial consultation. The age at which sexual intercourse first occurred was between 14 and 17, with a peak at 15-16 years of age. Most of the girls attending this Family Planning Center were told about it by friends or a sister (78%) and they rarely told their parents what they were doing (76%). Most of them (63%) preferred a woman doctor for a contraceptive consultation." (SUMMARY IN ENG)