Tartrat-resistente saure Phophatase (TRAP) Isoform 5b: ein neuer Serummarker der Knochenresorption bei Hämodialyse-Patienten

Die chronische, dialysepflichtige Niereninsuffizienz ist in den westlichen Industrie-ländern mitbedingt durch die ansteigende Zahl von Diabetikern eine zahlenmäßig zunehmende Erkrankung. In Deutschland liegt die Inzidenz der dialysepflichtigen Niereninsuffizienz bei 0,7/1000 Personen in der Bevölkerung und die Prävalenz bei 0,18/1000 Personen. Auch in den USA zeigt sich eine Zunahme der Patienten mit ter-minaler Niereninsuffizienz. Durch die steigende Anzahl der Patienten mit (dialyse-pflichtiger) Niereninsuffizienz steigt auch die Prävalenz der renalen Osteopathie, die bereits in frühen Stadien der Niereninsuffizienz bei einer Abnahme der glomerulären Filtratationsrate (GFR) auf 50 ml/min beginnt. Aufgrund der zunehmenden Häufigkeit werden metabolische Knochenerkrankungen im Jahre 2030 weltweit an 7. Stelle der chronischen Krankheiten stehen und werden daher von der WHO als „major health problem“ eingestuft. Zur Diagnostik der renalen Osteopathie stehen als diagnostische Verfahren die Anamnese, radiologische Untersuchungsverfahren und die invasive Diagnostik mittels Knochenbiopsie zur Verfügung. Allen genannten Untersuchungs-verfahren ist gemeinsam, dass sie nicht zur Erkennung von frühen Stadien der renalen Osteopathie geeignet sind. Die Lücke in diesem diagnostischen Dilemma schließen Laboruntersuchungen, die bei Beachtung von Einflüssen und richtiger Interpretation der Messwerte bereits vor auftreten morphologischer Veränderungen Pathologien des Knochenstoffwechsels anzeigen können. Ein stabiler und wenigen Einflüssen unter-legener Parameter in der Diagnostik der renalen Osteopathie ist die Tartratresistente saure Phophatase in ihrer Unterform 5b (im Folgenden als TRAP 5b bezeichnet). Diese Unterform wird von den Osteoklasten als aktives Enzym ins Blut abgegeben. In der vorliegenden Studie wurde bei initial 161 Patienten die Aktivität der TRAP 5b im Serum bestimmt. Der dabei verwendete Immunoassay (Firma Medac, Hamburg) detektiert ausschließlich Moleküle der aktiven TRAP 5b. Nicht erfasst werden die von aktivierten Makrophagen sezernierte inaktive Form des Enzyms und die Unterform 5a, welche bisher in Gaucherzellen der Milz nachgewiesen wurde. Damit ist die TRAP 5b ein spezifischer Marker für den Grad der Knochenresorption zum Zeitpunkt der Probenentnahme. Weiterhin wurden bei den Patienten die alkalische Phosphatase (AP) und das intakte Parathormon (iPTH) als Marker des Knochenstoffwechsels bestimmt. Zwischen den erhobenen Parametern und klinischen Daten, wie dem Alter der Patienten und der Dialysedauer wurden Korrelationen berechnet. Nach 6 Monaten erfolgte eine zweite Erhebung der Parameter, wobei aufgrund verschiedener Ursachen (Nierentransplantation, Tod, stationäre Behandlung, Wechsel des Dialysezentrums, verschiedene) 126 Patienten erneut untersucht werden konnten. Zwischen den initial erhobenen Parametern zeigten sich mit Werten von 0,406 (p<0,01) zwischen der AP und der TRAP 5b und 0,535 (p<0,01) zwischen iPTH und TRAP 5b gute hochsignifikante Korrelationen. Zwischen der Dialysedauer in Jahren bzw. dem Alter der Patienten und der TRAP 5b fand sich eine niedrigere Korrelation (0,264; p<0,01) bzw. ein gegenläufiger Zusammenhang mit einer hochsignifikanten Korrelation von –0,273 (p<0,01). Bei den 126 Patienten, die initial und nach 6 Monaten untersucht wurden, zeigten sich ähnliche Werte für die Korrelationen; Dialysedauer vs. TRAP 5b 0,298 (p<0,01) und Alter vs. TRAP 5b –0,254 (p<0,01). Nach 6 Monaten zeigten sich zwischen den erhobenen Parametern niedrigere Korrelationen als bei der ersten Untersuchung. Innerhalb der 6 Monate zwischen den beiden Untersuchungsterminen kam es zu einer signifikanten Abnahme (p<0,05) der TRAP 5b von 5,783,38 U/l auf 5,192,89 U/l. In der Gruppe der 126 Patienten zeigten sich zwei Untergruppen, in denen sich eine Ab- bzw. Zunahme der TRAP 5b um mehr als 50% des Ausgangswertes fand. Die Patienten der Gruppe mit Abnahme der Serumkonzentration der TRAP 5b haben mit 4,83,3 g/d vs. 0,6 1,0 g/d Al(OH)3 eine signifikant höhere Dosis an Phosphatbinder eingenommen, wobei sich bezüglich der eingenommenen Dosis an Calcitriol/Alphacalcitriol (0,160,54 g/Woche vs. 0,451,14 g/Woche) kein statistisch (p>0,05) signifikanter Unterschied findet. Beide Gruppen zeigen eine wenig ausgeprägte Änderung des iPTH-Spiegels in dieser Zeit. Weiterhin wurde in der Studie die Stabilität der TRAP 5b im Serum untersucht. Dabei zeigte sich, dass die TRAP 5b bei einer Lagerung bei –200C eine gute intraindividuelle Stabilität mit einer maximalen Abweichung von 5% hat und die Aktivität nicht durch die Länge des Dialyseintervalls beeinflusst wird Insgesamt konnte gezeigt werden, dass die Aktivität der TRAP 5b im Serum bei Patienten mit chronischer Niereninsuffizienz im Vergleich zu Gesunden erhöht ist, wobei sich zwischen Frauen und Männern keine signifikanten Unterschiede fanden. Unter einer Therapie mit antiresorptiven Medikamenten scheint die TRAP 5b im Vergleich zu anderen Parametern des Knochenstoffwechsels früher bzw. empfindlicher zu reagieren. Die Bestimmung der TRAP 5b erlaubt ein nicht invasives Monitoring der renalen Osteopathie u.a. bei Dialysepatienten

Capsule Endoscopy in Patients with Cardiac Pacemakers, Implantable Cardioverter Defibrillators, and Left Heart Devices: A Review of the Current Literature

Background and Study Aims. Capsule endoscopy is an established tool for investigation of the small intestine. Because of limited clinical experience in patients with cardiac devices, the Food and Drug Administration and the manufacturer recommended not to use capsule endoscopy in these patients. The vast majority of investigations did not reveal any interference between capsule endoscopy and cardiac devices. Methods. Studies investigating interference between CE and cardiac devices were analysed. For the review we considered studies published in English or German and indexed in Medline, as well as highly relevant abstracts. Results. In vitro and in vivo studies mainly revealed no interference between capsule endoscopy and cardiac devices. Technical data of capsule endoscopy (Given Imaging) reveal that interference with cardiac pacemakers and implantable cardioverter defibrillator is impossible. Telemetry can interfere with CE video. Conclusion. The clinical use of capsule endoscopy (Given Imaging) is unproblematic in patients with cardiac pacemakers

Capsule Endoscopy in Patients with Cardiac Pacemakers and Implantable Cardioverter Defibrillators: (Re)evaluation of the Current State in Germany, Austria, and Switzerland 2010

Background and Aims. The study was a repeated evaluation of the experience of capsule endoscopy (CE) in patients with cardiac pacemaker or implantable cardioverter defibrillator (ICD). Patients and Methods. A standardized questionnaire was sent by the manufactors Given Imaging and Olympus to all centers in Germany, Austria, and Switzerland providing capsule endoscopy service. The questionnaire covers the number of examined patients, monitoring during CE, check of the electric implants before and after CE, occurrence of arrhythmia, quality of CE video, complications, indication of CE, and type of institution. Results. Overall 580 questionnaires were sent to the users. 26/5% (Germany/Austria + Switzerland) of the questionnaires were sent back anonymously to the authors. 114 centers (82 hospitals, 11 surgeries, 21 without specification) replied. In 58 centers (51%), patients with cardiac pacemaker (n = 300) and ICDs (n = 80) underwent uneventful capsule endoscopy. The predominant indication (patients with CP 97%, patients with ICD 100%) was mid gastrointestinal bleeding. Conclusion. The results of our inquiry show that in spite of formal contraindication CE is increasingly applied in bleeding patients with cardiac pacemakers/ICDs and seems to be safe even in a large cohort

Arrhythmias in Patients With Pulmonary Hypertension; A Narrative Review of the Current Literature

Incidence and prognostic relevance of supraventricular arrhythmias were evaluated in nine studies. These studies investigated patients with different forms of pulmonary hypertension. Supraventricular arrhythmias were more often found in patients with group two pulmonary hypertension. Common findings in these patients were elevated right atrial pressure and diameters and reduced tricuspid annular plane systolic excursion (TAPSE). Elevations in other parameters like systolic pulmonary arterial pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance (PVR) were inconsistent. Most of the patients with arrhythmias suffered symptoms and improved after sinus rhythm (SR) was restored. The prognostic relevance of non-sustained ventricular tachycardia was evaluated in only one study. Non-sustained ventricular tachycardia does not seem to be prognostically relevant. Extending Holter electrocardiogram (ECG) monitoring over 24 hours up to 72 hours raises the detection rate of arrhythmias. Ablation of arrhythmias, especially atrial flutter and atrioventricular node reentry tachycardia, is feasible and safe in these patients

Heart rate variability is related to disease severity in children and young adults with pulmonary hypertension

Background: Pulmonary hypertension (PH) is frequently associated with an increase in sympathetic tone. This may adversely affect cardiac autonomic control. Knowledge about the clinical impact of autonomic dysfunction in patients with PH is limited. We aimed to assess whether parameters of heart rate variability (HRV) are related to disease severity in children with PH. Methods: Parameters of HRV [SDNN, standard deviation of normal-to-normal intervals and SDANN, standard deviation of mean values for normal-to-normal intervals over 5 min] were determined from Holter electrocardiograms of 17 patients with PH without active intracardial shunt (10 female, mean age 12.8 ± 8.7 years). Patients were allocated to two groups according to their disease severity: patients with moderate PH [ratio of pulmonary to systemic arterial pressure (PAP/SAP ratio) 0.75) (n = 6). An additional group of five adolescents with Eisenmenger syndrome (PAP/SAP ratio 1.13 ± 0.36) was included. Results: Children with severe PH had significantly lower values of HRV [SDNN (73.8 ± 21.1 vs. 164.9 ± 38.1 ms), SDANN (62.2 ± 19.0 vs. 139.5 ± 33.3 ms)] compared to patients with moderate PH (p = 0.0001 for all). SDNN inversely correlated with ratio of PAP/SAP of PH patients without shunt (r = -0.82; p = 0.0002). Eisenmenger patients showed no significant difference of HRV [SDNN 157.6 ± 43.2 ms, SDANN 141.2 ± 45.3 ms] compared to patients with moderate PH without shunt (p > 0.05 for all). Conclusion: According to our results, children with severe PH may have alterations in HRV. Since HRV appears to be related to disease severity, it may therefore serve as an additional diagnostic marker of PH. Remarkably, although Eisenmenger patients have systemic pulmonary arterial pressures, they seem to have preserved HRV, which might reflect a more favorable autonomic adaptation

Evaluation of the prognostic value of electrocardiography parameters and heart rhythm in patients with pulmonary hypertension

Background: Several studies have analyzed arrhythmias in patients with pulmonary hypertension (PH) and increased P-wave duration was identified as a risk factor for development of atrial fibrillation (AF). Methods: We retrospectively analyzed the incidence of arrhythmias in patients with an initial diagnosis of PH during long-term follow-up and assessed the prognostic value of electrocardiography (ECG) data. Data from 167 patients were analyzed (Dana Point Classification: Group 1: 59 patients, Group 2: 28 patients, Group 3: 39 patients, Group 4: 41 patients). Clinical, 6-min­ute walk distance test, echocardiography and right heart catheterization data were collected, and baseline/follow-up ECGs were analyzed. Results: Baseline ECGs revealed sinus rhythm in 137 patients. Thirteen patients had newly onset AF during follow-up. In 30 patients, baseline ECG showed AF. Patients with baseline AF showed higher atrial diameters and higher right atrial pressure. Patients with P-wave du­ration &gt; 0.11 s had shorter survival. Other ECG parameters (PQ-interval, QRS-width, QT-/ /QTc-interval) were not associated with survival. Mean survival times were 79.4 ± 5.4 months (sinus rhythm), 64.4 ± 12.9 months (baseline AF) and 58.8 ± 8.9 months (newly onset AF during follow-up) (p = 0.565). Conclusions: Atrial fibrillation predict adverse prognosis in patients with PH and a longer P-wave (&gt; 0.11 s) is associated with shorter survival time

Incidence and prognostic significance of malignant arrhythmias during (repetitive) Holter electrocardiograms in patients with pulmonary hypertension

BackgroundIn patients with pulmonary hypertension (PH), increased pulmonary vascular resistance (PVR) may lead to increased right ventricular afterload and cardiac remodelling, potentially providing the substrate for ventricular arrhythmias. Studies dealing with long term monitoring of patients with PH are rare. The present study evaluated the incidence and the types of arrhythmias retrospectively recorded by Holter ECG in patients with newly detected PH during a long-term Holter ECG follow-up. Moreover, their impact on patient survival was evaluated.Patients and methodsMedical records were screened for demographic data, aetiology of PH, incidence of coronary heart disease, level of brain natriuretic peptide (BNP), results from Holter ECG monitoring, 6-minute walk test distance, echocardiographic data and hemodynamic data derived from right heart catheterization. Two subgroups were analyzed: 1. patients (n = 65) with PH (group 1 + 4) and derivation of at least 1 Holter ECG within 12 months from initial detection of PH and 2. patients (all PH etiologies, n = 59) with 3 follow-up Holter ECGs. The frequency and complexity of premature ventricular contractions (PVC) was classified into “lower” and “higher” (=non sustained ventricular tachycardia, nsVT) burden.ResultsHolter ECG revealed sinus rhythm (SR) in most of the patients (n = 60). Incidence of atrial fibrillation (AFib) was low (n = 4). Patients with premature atrial contractions (PAC) tend to have a shorter period of survival (p = 0.098), PVC were not correlated with significant survival differences. During follow-up PAC and PVC were common in all PH groups. Holter ECG revealed non sustained ventricular tachycardia in 19/59 patients [(32.2%); n = 6 during first Holter-ECG, n = 13 during second/third Holter-ECG]. In all patients suffering from nsVT during follow-up previous Holter ECG revealed multiform/repetitive PVC. PVC burden was not linked to differences in systolic pulmonary arterial pressure, right atrial pressure, brain natriuretic peptide and results of six-minute walk test.ConclusionPatients with PAC tend to have a shortened survival. None of the evaluated parameters (BNP, TAPSE, sPAP) was correlated with the development of arrhythmias. Patients with multiform/repetitive PVC seem to be at risk for ventricular arrhythmias

How to misuse echo contrast

<p>Abstract</p> <p>Background</p> <p>Primary intracardiac tumours are rare, there are however several entities that can mimic tumours. Contrast echocardiography has been suggested to aid the differentiation of various suspected masses. We present a case where transthoracic echocardiography completely misdiagnosed a left atrial mass, partly due to use of echo contrast.</p> <p>Case presentation</p> <p>An 80 year-old woman was referred for transthoracic echocardiography because of one-month duration of worsening of dyspnoea. Transthoracic echocardiography displayed a large echodense mass in the left atrium. Intravenous injection of contrast (SonoVue, Bracco Inc., It) indicated contrast-enhancement of the structure, suggesting tumour. Transesophageal echocardiography revealed, however, a completely normal finding in the left atrium. Subsequent gastroscopy examination showed a hiatal hernia.</p> <p>Conclusion</p> <p>It is noteworthy that the transthoracic echocardiographic exam completely misdiagnosed what seemed like a left atrial mass, which in part was an effect of the use of echo contrast. This example highlights that liberal use of transoesophageal echocardiography is often warranted if optimal display of cardiac structures is desired.</p

Cápsula endoscópica e estudos imagiológicos contrastados: diferentes perspectivas para uma imagem mais completa do intestino delgado

Small bowel evaluation is a challenging task and has been revolutionized by high-quality contrasted sectional imaging (CT enterography - CTE) and magnetic resonance enterography (MRE) as well as by small bowel capsule endoscopy (SBCE).The decision of which technique to employ during the investigation of small bowel diseases is not always simple or straightforward. Moreover, contraindications may preclude the use of these techniques in some patients, and although they are noninvasive procedures, may present with various complications. SBCE plays a crucial role in the investigation of both obscure gastrointestinal bleeding and Crohn's disease, but it is also useful for surveillance of patients with Peutz-Jeghers syndrome, while CTE is very accurate in small bowel tumours and in established Crohn's Disease, and its use in patients presenting with gastrointestinal bleeding is increasing. MRE, an expensive and not widely available technique, is essential for the study of patients with Crohn's Disease, and presents an attractive alternative to SBCE in Peutz-Jeghers syndrome surveillance.These diagnostic modalities are often not competitive but synergistic techniques. Knowing their characteristics, strengths and limitations, indications, contraindications and potential complications, as well as the adaptation to local availability and expertise, is essential to better select which procedures to perform in each patient, both safely and effectively, in order to optimize management and improve patient outcomes.A investigação do intestino delgado, previamente difícil e limitada, sofreu uma revolução com o aparecimento de técnicas imagiológicas contrastadas de elevada qualidade, como a enterografia por tomografia axial computadorizada (enteroTC) e a enterografia por ressonância magnética (enteroRM), assim como pela enteroscopia por cápsula (EC). A decisão na escolha da técnica a utilizar nas diferentes patologias do intestino delgado não é na maioria das vezes simples ou óbvia. Adicionalmente, a presença de contraindicações pode restringir o uso destas técnicas em alguns doentes, e apesar de não serem consideradas técnicas invasivas, não são isentas de riscos e complicações. A EC tem um papel crucial na investigação da hemorragia digestiva de causa obscura e da doença de Crohn, mas tem-se revestido também de utilidade na vigilância de doentes com síndrome de Peutz-Jeghers; a enteroTC revelou uma elevada capacidade diagnóstica para neoplasias do intestino delgado e na doença de Crohn estabelecida, e a sua utilização na hemorragia digestiva de causa obscura tem vindo a expandir. A enteroRM, apesar de dispendiosa e de disponibilidade limitada, tem uma elevada eficácia no estudo da doença de Crohn, e é uma alternativa válida à EC no síndrome de Peutz-Jeghers. Estas técnicas diagnósticas são frequentemente singergísticas e complementares, ao invés de competitivas. O reconhecimento das suas características, das suas capacidades e limitações, assim como das indicações, contraindicações e potenciais complicações, e aliado à adaptação à disponibilidade e competências locais, é essencial na correcta escolha de procedimentos seguros e eficazes para cada doente, de forma a optimizar a abordagem e o prognóstico.(undefined)info:eu-repo/semantics/publishedVersio