The pathophysiology of thrombocytopenia in the syndrome of thrombocytopenia with absent radii (TAR) is not yet understood. We examined thrombopoietin (TPO) serum levels and the in vitro reactivity of platelets to TPO in five patients affected with TAR syndrome. We found elevated TPO serum levels in all patients tested, excluding a TPO production defect as cause for thrombocytopenia in TAR syndrome. In addition, we found similar expression of the TPO receptor c-Mpl on the surface of platelets from TAR patients (5 of 5) and a similar molecular weight of the receptor as compared with healthy controls (4 of 4). Platelet response to adenosine diphosphate or thrombin receptor agonist peptide SFLLRN (TRAP) was normal in TAR patients. However, in contrast to results with healthy controls we could show absence of in vitro reactivity of platelets from TAR patients to recombinant TPO as measured by testing TPO synergism to adenine diphosphate and TRAP in platelet activation. TPO induced tyrosine phosphorylation of platelet proteins was completely absent (3 of 4) or markedly decreased (1 of 4). Our results indicate that defective megakaryocytopoiesis/thrombocytopoiesis in TAR syndrome is not caused by a defect in TPO production but a lack of response to TPO in the signal transduction pathway of c-Mpl.
Depersonalization (DP), i.e., feelings of being detached from one's own mental processes or body, can be considered as a form of mental escape from the full experience of reality. This mental escape is thought to be etiologically linked with maltreatment during childhood. The detached state of consciousness in DP contrasts with certain aspects of mindfulness, a state of consciousness characterized by being in touch with the present moment. Against this background, the present article investigates potential connections between DP severity, mindfulness, and childhood trauma in a mixed sample of nonpatients and chronic nonmalignant pain patients. We found a strong inverse correlation between DP severity and mindfulness in both samples, which persisted after partialing out general psychological distress. In the nonpatient sample, we additionally found significant correlations between emotional maltreatment on the one hand and DP severity (positive) and mindfulness (negative) on the other. We conclude that the results first argue for an antithetical relationship between DP and certain aspects of mindfulness and thus encourage future studies on mindfulness-based interventions for DP and second throw light on potential developmental factors contributing to mindfulness.
Our meta-analysis of all available randomized evidence shows a survival benefit of ICD therapy for primary prevention in DCM. DANISH results suggest an attenuation of this ICD advantage when compared to contemporary medical and cardiac resynchronization therapy. Until larger trials have confirmed this finding, ICD therapy should remain the recommendation for primary prevention of SCD in DCM.
After PEG placement at the Medical Department of the University Hospital in Kiel, 210 patients (mean age 61.3 years; 137 men, 73 women) were prospectively followed-up for 133+/-181 days. Close-meshed evaluations of the development of nutritional status, long-term outcome, complications, subjective acceptability, patient care after discharge from the hospital, survival, and nutritional long-term problems were performed. The PEG procedure (duration 13.3+/-4.2 min) was carried out for neurological (42%), ear-nose-throat (28%), and internal medical (30%) indications. Procedure-related mortality was 0%, while altogether 3.8% severe and 20.0% mild complications were observed. Body weight decreased by a mean of 11.4+/-1.5 kg in the three months before and increased by 3.5+/-1.7 kg one year after PEG placement with no significant differences between malignant or benign underlying diseases. Individual subjective acceptability was excellent in 83%, sufficient in 15%, and poor in 2% of patients only. One-year survival rate was 34.3%. The various results of the present prospective study demonstrate that long-term enteral feeding via PEG is a safe, effective, easy-to-practice, and highly acceptable method with excellent long-term results and distinct improvement of nutritional status. Individual decisions for PEG placement should be considered much earlier and more frequently in appropriate patients.
Direct-acting antivirals (DAAs) are known victims (substrate) and perpetrators (cause) of drug–drug interactions (DDIs). These DAAs are used for the treatment of hepatitis C virus (HCV) infections and are highly effective drugs. Drugs used for cardiovascular risk management are frequently used by HCV-infected patients, whom also are treated with DAAs. Therefore, the aim of this review was to describe DDIs between cardiovascular drugs (CVDs) and DAAs. An extensive literature search was performed containing search terms for the marketed DAAs and CVDs (β-blocking agents, ACE inhibitors, angiotensin II antagonists, renin inhibitors, diuretics, calcium channel blockers, statins/ezetimibe, fibrates, platelet aggregation inhibitors, vitamin K antagonists, heparins, direct Xa inhibitors, nitrates, amiodarone, and digoxin). In particular, the drug labels from the European Medicines Agency and the US Food and Drug Administration were used. A main finding of this review is that CVDs are mostly victims of DDIs with DAAs. Therefore, when possible, monitoring of pharmacodynamics is recommended when coadministering these drugs with DAAs. Nevertheless, it is sometimes better to discontinue a drug on a temporary basis (statins, ezetimide). The DAAs are victims of DDIs in combination with bisoprolol, carvedilol, labetalol, verapamil, and gemfibrozil. Despite there are many DDIs predicted in this review, most of these DDIs can be managed by monitoring the efficacy and toxicity of the victim drug or by switching to another CVD/DAA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.