scholarly journals Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle

2015 ◽  
Vol 112 (47) ◽  
pp. 14694-14699 ◽  
Author(s):  
Christian Meisel ◽  
Andreas Schulze-Bonhage ◽  
Dean Freestone ◽  
Mark James Cook ◽  
Peter Achermann ◽  
...  

Pathological changes in excitability of cortical tissue commonly underlie the initiation and spread of seizure activity in patients suffering from epilepsy. Accordingly, monitoring excitability and controlling its degree using antiepileptic drugs (AEDs) is of prime importance for clinical care and treatment. To date, adequate measures of excitability and action of AEDs have been difficult to identify. Recent insights into ongoing cortical activity have identified global levels of phase synchronization as measures that characterize normal levels of excitability and quantify any deviation therefrom. Here, we explore the usefulness of these intrinsic measures to quantify cortical excitability in humans. First, we observe a correlation of such markers with stimulation-evoked responses suggesting them to be viable excitability measures based on ongoing activity. Second, we report a significant covariation with the level of AED load and a wake-dependent modulation. Our results indicate that excitability in epileptic networks is effectively reduced by AEDs and suggest the proposed markers as useful candidates to quantify excitability in routine clinical conditions overcoming the limitations of electrical or magnetic stimulation. The wake-dependent time course of these metrics suggests a homeostatic role of sleep, to rebalance cortical excitability.

1979 ◽  
Vol 42 (04) ◽  
pp. 1193-1206 ◽  
Author(s):  
Barbara Nunn

SummaryThe hypothesis that platelet ADP is responsible for collagen-induced aggregation has been re-examined. It was found that the concentration of ADP obtaining in human PRP at the onset of aggregation was not sufficient to account for that aggregation. Furthermore, the time-course of collagen-induced release in human PRP was the same as that in sheep PRP where ADP does not cause release. These findings are not consistent with claims that ADP alone perpetuates a collagen-initiated release-aggregation-release sequence. The effects of high doses of collagen, which released 4-5 μM ADP, were not inhibited by 500 pM adenosine, a concentration that greatly reduced the effect of 300 μM ADP. Collagen caused aggregation in ADP-refractory PRP and in platelet suspensions unresponsive to 1 mM ADP. Thus human platelets can aggregate in response to collagen under circumstances in which they cannot respond to ADP. Apyrase inhibited aggregation and ATP release in platelet suspensions but not in human PRP. Evidence is presented that the means currently used to examine the role of ADP in aggregation require investigation.


2018 ◽  
Vol 68 (suppl 1) ◽  
pp. bjgp18X696713
Author(s):  
David Seamark ◽  
Deborah Davidson ◽  
Helen Tucker ◽  
Angela Ellis-Paine ◽  
Jon Glasby

BackgroundIn 2000 20% of UK GPs had admitting rights to community hospitals. In subsequent years the number of GPs engaged in community hospital clinical care has decreased.AimWhat models of medical care exist in English community hospitals today and what factors are driving changes?MethodInterviews with community hospital clinical staff conducted as part of a multimethod study of the community value of community hospitals.ResultsSeventeen interviews were conducted and two different models of medical care observed: GP led and Trust employed doctors. Factors driving changes were GP workload and recruitment challenges; increased medical acuity of patients admitted; fewer local patients being admitted; frustration over the move from ‘step-up’ care from the local community to ‘step-down’ care from acute hospitals; increased burden of GP medical support; inadequate remuneration; and GP admission rights removed due to bed closures or GP practices withdrawing from community hospital work.ConclusionMultiple factors have driven changes in the role of GP community hospital clinicians with a consequent loss of GP generalist skills in the community hospital setting. The NHS needs to develop a focused strategy if GPs are to remain engaged with community hospital care.


Author(s):  
MT Congedo ◽  
GM Ferretti ◽  
D Nachira ◽  
MA Pennisi

Background: In symptomatic patients, admitted in emergency department for acute chest pain and dyspnea, who require an urgent treatment, a rapid diagnosis and prompt management of massive pleural effusion or hemothorax can be lifesaving. The aim of this review was to summarize the current diagnostic and therapeutic approaches for the management of the main types of pleural effusions that physicians can have in an emergency department setting. Methods: Current literature about the topic was reviewed and critically reported, adding the experience of the authors in the management of pleural effusions in emergency settings. Results: The paper analyzed the main types of pleural effusions that physicians can have to treat. It illustrated the diagnostic steps by the principal radiological instruments, with a particular emphasis to the role of ultrasonography, in facilitating diagnosis and guiding invasive procedures. Then, the principal procedures, like thoracentesis and insertion of small and large bore chest drains, are indicated and illustrated according to the characteristics and the amount of the effusion and patient clinical conditions. Conclusion: The emergency physician must have a systematic approach that allows rapid recognition, clinical cause identification and definitive management of potential urgent pleural effusions.


Author(s):  
Marian Tanofsky-Kraff ◽  
Denise E. Wilfley

Interpersonal psychotherapy (IPT) is a focused, time-limited treatment that targets interpersonal problem(s) associated with the onset and/or maintenance of EDs. IPT is supported by substantial empirical evidence documenting the role of interpersonal factors in the onset and maintenance of EDs. IPT is a viable alternative to cognitive behavior therapy for the treatment of bulimia nervosa and binge eating disorder. The effectiveness of IPT for the treatment of anorexia nervosa requires further investigation. The utility of IPT for the prevention of obesity is currently being explored. Future research directions include enhancing the delivery of IPT for EDs, increasing the availability of IPT in routine clinical care settings, exploring IPT adolescent and parent–child adaptations, and developing IPT for the prevention of eating and weight-related problems that may promote full-syndrome EDs or obesity.


Author(s):  
Young-Min Han ◽  
Min Sun Kim ◽  
Juyeong Jo ◽  
Daiha Shin ◽  
Seung-Hae Kwon ◽  
...  

AbstractThe fine-tuning of neuroinflammation is crucial for brain homeostasis as well as its immune response. The transcription factor, nuclear factor-κ-B (NFκB) is a key inflammatory player that is antagonized via anti-inflammatory actions exerted by the glucocorticoid receptor (GR). However, technical limitations have restricted our understanding of how GR is involved in the dynamics of NFκB in vivo. In this study, we used an improved lentiviral-based reporter to elucidate the time course of NFκB and GR activities during behavioral changes from sickness to depression induced by a systemic lipopolysaccharide challenge. The trajectory of NFκB activity established a behavioral basis for the NFκB signal transition involved in three phases, sickness-early-phase, normal-middle-phase, and depressive-like-late-phase. The temporal shift in brain GR activity was differentially involved in the transition of NFκB signals during the normal and depressive-like phases. The middle-phase GR effectively inhibited NFκB in a glucocorticoid-dependent manner, but the late-phase GR had no inhibitory action. Furthermore, we revealed the cryptic role of basal GR activity in the early NFκB signal transition, as evidenced by the fact that blocking GR activity with RU486 led to early depressive-like episodes through the emergence of the brain NFκB activity. These results highlight the inhibitory action of GR on NFκB by the basal and activated hypothalamic-pituitary-adrenal (HPA)-axis during body-to-brain inflammatory spread, providing clues about molecular mechanisms underlying systemic inflammation caused by such as COVID-19 infection, leading to depression.


2021 ◽  
Vol 22 (13) ◽  
pp. 7072
Author(s):  
Andrea Toniato ◽  
Chiara Gamba ◽  
Jan Walter Schroeder ◽  
Valeria Fabbri ◽  
Scarlett Valeria Bernal Ortiz ◽  
...  

DRESS/DiHS is a complex and potentially fatal drug reaction. Little is known about risk factors and elements that can help to identify patients with a severe reaction early. The aim of the study was to investigate those factors favoring the disease and its severity by analyzing the clinical conditions and therapies preceding the reaction. We conducted a retrospective analysis on patients admitted to our center between 2010 and 2020 who were discharged with a diagnosis of DRESS. We used the RegiSCAR diagnostic criteria. We defined the severity of DRESS using the criteria of Mizukawa et al. We included 25 patients (15 females) with a median age of 66 years. Skin involvement, eosinophilia, and liver injury were the most important aspects. Allopurinol was found to be the most involved drug. Reaction severity was significantly associated with the number of daily medications (p=0.0067) and an age of at least 68 years (p=0.013). In addition, 75% of severe cases had at least three comorbidities in history, and most of the severe cases were female. In our study the advanced age, the high number of comorbidities and home therapies, and the inflammatory state were found to be predisposing elements to the development of the disease and its severity.


2021 ◽  
pp. 147775092110114
Author(s):  
George Slade Mellgard ◽  
Jacob M Appel

Economic motivations are key drivers of human behavior. Unfortunately, they are largely overlooked in literature related to medical decisionmaking, particularly with regard to end-of-life care. It is widely understood that the directions of a proxy acting in bad faith can be overridden. But what of cases in which the proxy or surrogate appears to be acting in good faith to effectuate the patient’s values, yet doing so directly serves the decision-maker’s financial interests? Such situations are not uncommon. Many patients care as deeply about economic wellbeing of their families as they do for their own lives and health. This brief work examines three scenarios that raise ethical issues regarding the role of pecuniary motives in making critical medical decisions. Each scenario presents a potential financial conflict of interest between an incapacitated patient and a third-party decision-maker and offers a framework for integrating ethical and legal concerns into clinical care. It is our hope that this work prepares physicians for unexpected ethical conflicts of interest and enables them to further the interests of his or her patients.


2019 ◽  
Vol 26 (11) ◽  
pp. 1385-1388 ◽  
Author(s):  
William E Yang ◽  
Lochan M Shah ◽  
Erin M Spaulding ◽  
Jane Wang ◽  
Helen Xun ◽  
...  

Abstract Mobile health (mHealth) interventions have demonstrated promise in improving outcomes by motivating patients to adopt and maintain healthy lifestyle changes as well as improve adherence to guideline-directed medical therapy. Early results combining behavioral economic strategies with mHealth delivery have demonstrated mixed results. In reviewing these studies, we propose that the success of a mHealth intervention links more strongly with how well it connects patients back to routine clinical care, rather than its behavior modification technique in isolation. This underscores the critical role of clinician-patient partnerships in the design and delivery of such interventions, while also raising important questions regarding long-term sustainability and scalability. Further exploration of our hypothesis may increase opportunities for multidisciplinary clinical teams to connect with and engage patients using mHealth technologies in unprecedented ways.


Sign in / Sign up

Export Citation Format

Share Document