Robot-assisted epicardial ablation of the pulmonary veins: is a completed isolation necessary?

AIMS: To study the feasibility and electrophysiological efficacy of minimally invasive beating heart ablation of the pulmonary veins (PVs) via a robot-assisted single-sided approach. BACKGROUND: PV isolation by minimally invasive epicardial ablation may offer a new treatment for patients with lone atrial fibrillation (AF). However, complete PV isolation has been shown to be difficult to obtain. METHODS AND RESULTS: In 14 mongrel dogs, robot-assisted epicardial microwave ablation was performed on the beating heart by a single-sided right chest approach. Isolation of all PVs was performed in two steps to study the effect of an incomplete and a complete isolation on AF. AF was studied by random and burst pacing. Incremental pacing was performed to study conduction characteristics across the lesions. Opening of the pericardial reflections, introduction of the catheter and ablation were robotically feasible by a single-sided approach in 11 dogs. The AF duration decreased from 6.6+/-4.1 to 1.3+/-0.8 s (P=0.03) and 1.6+/-1.6 s (P=0.04 compared with control) after incomplete and completed isolation of the PVs. The AF cycle length increased from 134+/-5 to 141+/-5 and 145+/-8 ms (P=0.03) after incomplete and complete isolation, respectively. Several incomplete lesions showed 2:1 exit and/or entrance block during incremental pacing. After complete isolation, AF was no longer inducible from the PVs. CONCLUSION: Epicardial PV isolation can be successfully performed by a single-sided robot-assisted approach. The effect of PV ablation on AF is not an all or none phenomenon. Incomplete isolation already decreases AF duration and lengthens the AF cycle length. However, complete isolation is necessary to prevent AF induction by triggering from the isolated area.     

Albuminuria, but not estimated glomerular filtration rate, is associated with maladaptive arterial remodeling: the Hoorn Study

OBJECTIVE: Arterial remodeling aims to maintain a constant circumferential wall stress (sigmac). A failing remodeling process is associated with stroke. Data on the relationship between chronic kidney disease and arterial remodeling are scarce. METHODS: We investigated the association between a lower glomerular filtration rate (GFR) and microalbuminuria with arterial remodeling of the common carotid artery (CCA) in a population-based study of 806 patients. CCA properties including intima-media thickness and interadventitial diameter (IAD) were assessed. Lumen diameter, circumferential wall tension (CWT), and circumferential wall stress (sigmac) were calculated. GFR was estimated (eGFR) by the Modification of Diet in Renal Disease formula. Albuminuria was expressed as urinary albumin/creatinine ratio. RESULTS: Mean eGFR was 60.3 (+/-10.8) ml/min/1.73 m2; median urinary albumin/creatinine ratio was 0.57 (range 0.10-26.6 mg/mmol). After adjustment for age, sex, glucose tolerance status, and prevalent cardiovascular disease, eGFR was not independently associated with CCA properties. A greater urinary albumin/creatinine ratio (per quartile) was associated with a greater lumen diameter [regression coefficient beta with 95% confidence interval, 0.14 (0.08-0.20; P < 0.01)], IAD [0.15 (0.09-0.21; P < 0.01)], CWT [0.95 (0.52-1.38; P < 0.01)], and sigmac [1.7 (0.5-2.9; P < 0.01)] but not with a greater IMT [0.01 (-0.002-0.02; P = 0.12)]. Additional adjustments for mean arterial pressure, pulse pressure, and eGFR did not change the results. CONCLUSION: Greater albuminuria is independently associated with an increase in lumen diameter and IAD of the CCA. In addition, greater albuminuria is associated with a maladaptive carotid remodeling process as shown by an increase in CWT and sigmac. These findings may explain, why microalbuminuria is associated with a greater risk of cardiovascular disease and especially stroke.     

Quality of Self-Care of Patients with Asthma

In order to assess the quality of self-care of asthmatic patients in family practice, 150 patients were asked what they did when they felt an attack of asthma coming on. Twenty-four percent said they took no medication. Of the remaining 114 patients, only 49 took appropriate medication. Of these, however, most were not able to demonstrate correct use of their inhaler. This poor quality of self-care may contribute to the undertreatment of asthma in family practice. To improve the quality of care of asthmatic patients, comprehensive treatment is recommended, with the emphasis on improving self-care skills.     

Major Depressive Disorder and Emotion-Related Impulsivity: Are Both Related to Cognitive Inhibition?

Previous studies indicate that emotion-relevant impulsivity is related to depression and relatedly, suicidal ideation and behavior. Little is known, however, about underlying mechanisms driving this impulsivity. We hypothesized that participants diagnosed with depression would show difficulties with emotion-related impulsivity and inhibition compared to controls, and that there would be a link between inhibition deficits and emotion-relevant impulsivity. To test these hypotheses, 60 participants diagnosed with lifetime major depressive disorder (MDD; 47 full-remission, 8 current MDD, 5 partial remission) and 100 nondepressed controls completed measures of impulsivity and current depressive symptoms, underwent a negative mood induction, and completed tasks that assessed components of inhibition: the ability to suppress pre-potent responses (antisaccade task) and the ability to resist interference (word-naming task). Although people with a history of MDD did not show cognitive inhibition deficits, they did endorse more emotion-related impulsivity, which in turn related to difficulty suppressing pre-potent responses. Limitations, as well as implications for future research and treatment are discussed.     

Synergistic interaction of the histone deacetylase inhibitor SAHA with the proteasome inhibitor bortezomib in mantle cell lymphoma

Objectives:  Mantle cell lymphoma (MCL) is an incurable B cell lymphoma, and novel treatment strategies are urgently needed. We evaluated the effects of combined treatment with the proteasome inhibitor bortezomib and the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) on MCL. Bortezomib acts by targeting the proteasome, and – among other mechanisms – results in a reduced nuclear factor-kappa B (NF-κB) activity. HDACi promote histone acetylation, and also interfere with NF-κB signaling.
Methods:  Human MCL cell lines (JeKo-1, Granta-519 and Hbl-2) were exposed to bortezomib and/or SAHA. Cell viability and apoptosis were quantified by the MTT and annexin-V assay, respectively. Reactive oxygen species (ROS) were analyzed using the fluorophore H₂DCFDA. In addition, activated caspases, proteasome- and NF-κB activity were quantified.
Results:  Combined incubation with bortezomib and SAHA resulted in synergistic cytotoxic effects, as indicated by combination index values <1 using the median effect method of Chou and Talalay. The combination of both inhibitors led to a strong increase in apoptosis as compared to single agents and was accompanied by enhanced ROS generation, while each agent alone only modestly induced ROS. The free radical scavenger N -acetyl- l -cysteine blocked the ROS generation and reduced the apoptosis significantly. In addition, coexposure of bortezomib and SAHA led to increased caspase-3, -8 and -9 activity, marked reduction of proteasome activity and decrease of NF-κB activity.
Conclusions:  This is the first report giving evidence that SAHA and bortezomib synergistically induce apoptosis in MCL cells. These data build the framework for clinical trials using combined proteasome and histone deacetylase inhibition in the treatment of MCL.     

Visceral leishmaniasis: current status of control,diagnosis, and treatment,and a proposed research and development agenda

Visceral leishmaniasis is common in less developed countries, with an estimated 500000 new cases each year. Because of the diversity of epidemiological situations, no single diagnosis, treatment, or control will be suitable for all. Control measures through case finding, treatment, and vector control are seldom used, even where they could be useful. There is a place for a vaccine, and new imaginative approaches are needed. HIV co-infection is changing the epidemiology and presents problems for diagnosis and case management. Field diagnosis is difficult; simpler, less invasive tests are needed. Current treatments require long courses and parenteral administration, and most are expensive. Resistance is making the mainstay of treatment, agents based on pentavalent antimony, useless in northeastern India, where disease incidence is highest. Second-line drugs (pentamidine and amphotericin B) are limited by toxicity and availability, and newer formulations of amphotericin B are not affordable. The first effective oral drug, miltefosine, has been licensed in India, but the development of other drugs in clinical phases (paromomycin and sitamaquine) is slow. No novel compound is in the pipeline. Drug combinations must be developed to prevent drug resistance. Despite these urgent needs, research and development has been neglected, because a disease that mainly affects the poor ranks as a low priority in the private sector, and the public sector currently struggles to undertake the development of drugs and diagnostics in the absence of adequate funds and infrastructure. This article reviews the current situation and perspectives for diagnosis, treatment, and control of visceral leishmaniasis, and lists some priorities for research and development.     

Brief Report: Associations Between Autism Characteristics,Written and Spoken Communication Skills,and Social Interaction Skills in Preschool-Age Children on the Autism Spectrum

Journal of Autism and Developmental Disorders - We used parent-report data from a prospective longitudinal study to better understand the early strengths in written skills often observed in...     

Low levels of frailty in HIV-positive older adults on antiretroviral therapy in northern Tanzania

Journal of NeuroVirology - There are over 3 million people in sub-Saharan Africa (SSA) aged 50 and over living with HIV. HIV and combined antiretroviral therapy (cART) exposure may accelerate the...