The use of Macitentan in Fontan circulation: a case report.

BACKGROUND: The Fontan circulation, a result of a palliative procedure in patients with single systemic ventricles, is defined by chronically elevated pulmonary vascular resistance. When traditional heart failure therapies fail, pharmacological agents that reduce pulmonary artery pressures may be used. These include endothelial-receptor antagonists, prostanoids and phosphodiesterase type 5 inhibitors. We report the first use of macitentan, an endothelin-receptor antagonist, in a patient with a Fontan circulation. CASE PRESENTATION: We describe the case of a 50 year old female with tricuspid atresia and transposition of the great arteries. Following complex surgery as a child, she subsequently underwent a fenestrated modified atrial pulmonary Fontan operation which was later converted to a total cavopulmonary anastomosis Fontan circulation. Due to failure of various medications to relieve her worsening symptoms, she was commenced on macitentan in April 2016. Few months later, she demonstrated a significant symptomatic improvement and associated increase in her incremental shuttle walking test distance. CONCLUSIONS: Macitentan has slower receptor dissociation kinetics compared to other endothelin-receptor antagonists, leading to enhanced pharmacological activity with promising effects in patients with pulmonary arterial hypertension. The patient we report has shown considerable improvement in exercise capacity following introduction of this medication and thus we suggest further randomised trials to establish the role of different endothelin-receptor antagonists in the management of the Fontan circulation

A cross-sectional study of Victorian mobile intensive care ambulance paramedics knowledge of the Valsalva manoeuvre

<p>Abstract</p> <p>Background</p> <p>The Valsalva Manoeuvre (VM) is a primary measure for terminating haemodynamically stable supraventricular tachycardia (SVT) in the emergency care setting. The clinical use and termination success of the VM in the prehospital setting has not been investigated to date. The objective of this study was to determine Melbourne Mobile Intensive Care Ambulance (MICA) Paramedic knowledge of the VM, and to compare this understanding with an evidence-based model of VM performance.</p> <p>Methods</p> <p>A cross-sectional study in the form of a face-to-face interview was used to determine Melbourne MICA Paramedic understanding of VM instruction between January and February, 2008. The results were then compared with an evidence-based model of VM performance to ascertain compliance with the three criteria of position, pressure and duration. Ethics approval was granted.</p> <p>Results</p> <p>There were 28 participants (60.9%) who elected a form of supine posturing, some 23 participants (50%) selected the syringe method of pressure generation, with 16 participants (34.8%) selecting the "as long as you can" option for duration. On comparison, one out of 46 MICA Paramedics correctly identified the three evidence-based criteria.</p> <p>Conclusions</p> <p>The formal education of Melbourne's MICA Paramedics would benefit from the introduction of an evidence based model of VM performance, which would impact positively on patient care and may improve reversion success in the prehospital setting. The results of this study also demonstrate that an opportunity exists to promote the evidence-based VM criteria across the primary emergency care field.</p

Seroprevalence of hepatitis C in type 2 diabetes: evidence for a positive association

<p>Abstract</p> <p>Background</p> <p>There is a growing body of literature on the relationship of Hepatitis C virus infection (HCV) and type 2 diabetes mellitus (T2DM). However, there are certain gaps in literature and the data is inconclusive. This study was, therefore, carried out to determine the prevalence of HCV infection in diabetic patients and to elucidate the presence of any possible relationship between HCV and T2DM in this region.</p> <p>Methods</p> <p>Serologic testing for anti-HCV antibody was done on a sample of 3000 individuals with T2DM visiting Diabetes Clinic of Nishtar Medical College Hospital, Multan and 10,000 volunteer blood donors visiting blood bank of the same hospital during the study period using Accurate rapid immunochromatographic kits which was later confirmed by using Chemelex S.A third generation ELISA kit for positive cases. Data about various variables was collected from diabetic patients using a structured questionnaire after taking informed consent.</p> <p>Results</p> <p>Prevalence rate of 13.7% for HCV infection was recorded among subjects having T2DM with seropositivity rate of 4.9% among the control group of volunteer blood donors without diabetes. The patients with T2DM were more likely to have HCV infection as compared to the control group (OR = 3.03, 95%CI = 2.64-3.48, p = 0.001). Diabetic patients with age above 55 years had higher prevalence rate as compared to younger individuals. Male patients had significantly high seropositivity as compared to female patients (15.3% vs. 12.4%, p = 0.02). Those with duration of diabetes 11 years and above and the ones with good glycemic control had higher seroprevalence rates of 18.2% and 18.7% respectively. There was no statistically significant difference among subjects when the distribution of HCV was studied on the basis of marital status, locality, or family history of diabetes.</p> <p>Conclusions</p> <p>The results show that there is a strong association between HCV and T2DM in the region as evident from significantly higher prevalence of HCV infection in diabetics as compared to the control group in the present study.</p

Retinoids Regulate the Formation and Degradation of Gap Junctions in Androgen-Responsive Human Prostate Cancer Cells

The retinoids, the natural or synthetic derivatives of Vitamin A (retinol), are essential for the normal development of prostate and have been shown to modulate prostate cancer progression in vivo as well as to modulate growth of several prostate cancer cell lines. 9-cis-retinoic acid and all-trans-retinoic acid are the two most important metabolites of retinol. Gap junctions, formed of proteins called connexins, are ensembles of intercellular channels that permit the exchange of small growth regulatory molecules between adjoining cells. Gap junctional communication is instrumental in the control of cell growth. We examined the effect of 9-cis-retinoic acid and all-trans retinoic acid on the formation and degradation of gap junctions as well as on junctional communication in an androgen-responsive prostate cancer cell line, LNCaP, which expressed retrovirally introduced connexin32, a connexin expressed by the luminal cells and well-differentiated cells of prostate tumors. Our results showed that 9-cis-retinoic acid and all-trans retinoic acid enhanced the assembly of connexin32 into gap junctions. Our results further showed that 9-cis-retinoic acid and all-trans-retinoic acid prevented androgen-regulated degradation of gap junctions, post-translationally, independent of androgen receptor mediated signaling. Finally, our findings showed that formation of gap junctions sensitized connexin32-expressing LNCaP cells to the growth modifying effects of 9-cis-retinoic acid, all-trans-retinoic acid and androgens. Thus, the effects of retinoids and androgens on growth and the formation and degradation of gap junctions and their function might be related to their ability to modulate prostate growth and cancer

Acute kidney disease and renal recovery : consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of > 90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD

Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia

Peer reviewe

Shot noise in mesoscopic systems

This is a review of shot noise, the time-dependent fluctuations in the electrical current due to the discreteness of the electron charge, in small conductors. The shot-noise power can be smaller than that of a Poisson process as a result of correlations in the electron transmission imposed by the Pauli principle. This suppression takes on simple universal values in a symmetric double-barrier junction (suppression factor 1/2), a disordered metal (factor 1/3), and a chaotic cavity (factor 1/4). Loss of phase coherence has no effect on this shot-noise suppression, while thermalization of the electrons due to electron-electron scattering increases the shot noise slightly. Sub-Poissonian shot noise has been observed experimentally. So far unobserved phenomena involve the interplay of shot noise with the Aharonov-Bohm effect, Andreev reflection, and the fractional quantum Hall effect.Comment: 37 pages, Latex, 10 figures (eps). To be published in "Mesoscopic Electron Transport," edited by L. P. Kouwenhoven, G. Schoen, and L. L. Sohn, NATO ASI Series E (Kluwer Academic Publishing, Dordrecht

Remifentanil-propofol analgo-sedation shortens duration of ventilation and length of ICU stay compared to a conventional regimen: A centre randomised, cross-over, open-label study in the Netherlands

Objective: Compare duration of mechanical ventilation (MV), weaning time, ICU-LOS (ICU-LOS), efficacy and safety of remifentanil-based regimen with conventional sedation and analgesia. Design: Centre randomised, open-label, crossover, 'real-life' study. Setting: 15 Dutch hospitals. Patients: Adult medical and post-surgical ICU patients with anticipated short-term (2-3 days) MV. Interventions: Patient cohorts were randomised to remifentanil-based regimen (n = 96) with propofol as required, for a maximum of 10 days, or to conventional regimens (n = 109) of propofol, midazolam or lorazepam combined with fentanyl or morphine. Measurements and main results: Outcomes were weaning time, duration of MV, ICU-LOS, sedation- and analgesia levels, intensivist/ICU nurse satisfaction, adverse events, mean arterial pressure, heart rate. Median duration of ventilation (MV) was 5.1 days with conventional treatment versus 3.9 days with remifentanil (NS). The remifentanil-based regimen reduced median weaning time by 18.9 h (P = 0.0001). Median ICU-LOS was 7.9 days versus 5.9 days, respectively (NS). However, the treatment effects on duration of MV and ICU stay were time-dependent: patients were almost twice as likely to be extubated (P = 0.018) and discharged from the ICU (P = 0.05) on day 1-3. Propofol doses were reduced by 20% (P = 0.05). Remifentanil also improved sedation-agitation scores (P < 0.0001) and intensivist/ICU nurse satisfaction (P < 0.0001). All other outcomes were comparable. Conclusions: In patients with an expected short-term duration of MV, remifentanil significantly improves sedation and agitation levels and reduces weaning time. This contributes to a shorter duration of MV and ICU-LOS