Novel KCNQ2 Mutation in a Large Emirati Family With Benign Familial Neonatal Seizures

Mutations in voltage-gated potassium channel Kv7.2 are responsible for benign familial neonatal seizures type 1, a rare monogenic autosomal dominant inherited epilepsy syndrome. We describe a novel mutation (c.1126_1127delA) in exon 9 of KCNQ2, the gene encoding for the Kv7.2 channel, in a large Emirati family with benign familial neonatal seizures type 1. The mutation leads to a frameshift at amino acid position 376, triggering loss of function and haploinsufficiency. Patients with this mutation manifest repeated clonic seizures with normal interictal electroencephalograms and favorable prognoses. Signs occur within the first days of age, lingering well into puberty. KCNQ2 mutation screening, alongside genetic counseling, should be included in diagnostic evaluations of neonatal epileptic patients, potentially sparing the need for unnecessary investigations and treatment. To our knowledge, this report is the first of a KCNQ2 mutation in an Emirati family with benign familial neonatal seizures type 1.     

Enhancement of levodopa stability when complexed with β-cyclodextrin in transdermal patches

Abstract

Levodopa is a promising candidate for administration via the transdermal route because it exhibits a short plasma half-life and has a small window of absorption in the upper section of the small intestine. The aim of this study was to prepare stable levodopa transdermal patches. Both xanthan gum and Carbopol 971 polymers were selected with ethylcellulose constituting the backing layer of the prepared patches. The effect of adding β-cyclodextrin on the prepared patches was investigated. The uniformity in thickness, weight and content of the studied patches was acceptable. Physicochemical characterization revealed that there was no interaction between levodopa and the applied polymer. The results proved that levodopa precipitated as an amorphous form in carbopol patches. Controlled drug release was achieved for all the tested patches over a 6?h period. However, increased permeation was achieved for the carbopol patches. Although cyclodextrin did not enhance levodopa permeation, the stability study confirmed that levodopa stability was enhanced when complexed with β-cyclodextrin. The cumulative amount of drug released from carbopol patches is slightly higher than that of xanthan patches. The optimal stability was achieved in the carbopol/levodopa:β-cyclodextrin patch. The levodopa-β-cyclodextrin complex was successfully characterized using X-ray diffraction, NMR analysis and molecular dynamics simulations. In conclusion, carbopol/levodopa:β-cyclodextrin patches can be considered as a promising stable and effective transdermal drug-delivery system.     

Survival Results After Implantation of Intrapericardial Third‐Generation Centrifugal Assist Device: An INTERMACS‐Matched Comparison Analysis

Reports on third‐generation centrifugal intrapericardial pumps (HeartWare International, Inc., Framingham, MA, USA) have shown better survival results than the previous‐generation devices. However, outcomes depending on the preoperative level of stability can substantially differ, resulting in a limited analysis of potentialities and drawbacks of a given device. In the present study we sought to compare in our single‐center experience the survival results of this third‐generation device with previous left ventricular systems taking into account the different preoperative Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) levels. Between February 1993 and March 2012, 287 patients underwent assist device implantation in our university hospital (INTERMACS Level 1‐2 = 158 patients; INTERMACS Level 3‐4‐5 = 129 patients). Assist devices implanted were: Group A (HVAD HeartWare, n = 52), group B (previous continuous‐flow ventricular assist device [VAD], InCor [Berlin Heart, Berlin, Germany], n = 37; VentrAssist [VentraCor, Inc., Chatswood, NSW, Australia], n = 7; DeBakey [MicroMed Cardiovascular, Inc., Houston, TX, USA], n = 32), and group C (pulsatile systems, n = 159). After cumulative support duration of 54 436 days and a mean follow‐up of 6.21 ± 7.46 months (range 0–45.21 months), log‐rank analysis revealed a survival for group A of 82.0%, 70.4%, and 70.4%; for group B of 84.0%, 48.2%, 33.7%; and for group C of 71.6%, 46.1%, 33.8%, at 1, 12, and 24 months respectively, with a significantly (P = 0.013) better outcome for group A. When stratifying the survival on the basis of INTERMACS level, no significant survival improvement was observed among all patients who underwent VAD implantation in INTERMACS 1‐2 (P = 0.47). However, among patients who underwent elective VAD implantation (INTERMACS 3‐4‐5), group A had a significantly better outcome (P = 0.005) compared with the other INTERMACS‐matched groups (B,C) with a survival rate of 88.8% in group A versus 34.2% in group B and 45.6% in group C at 24 months, respectively. Elective HVAD system implantation shows improved survival benefit over the other INTERMACS‐matched devices. Moreover, preoperative unstable hemodynamics resulted in a poor prognosis independently from the pump generation.     

Comparison between short- and long-acting erythropoiesis-stimulating agents in hemodialysis patients: target hemoglobin,variability, and outcome

Purpose

Maintaining target hemoglobin (Hb) with minimal variability is a challenge in hemodialysis (HD) patients. The aim of this study is to compare the long- and short-acting erythropoietin-stimulating agents such as Aranesp and Eprex in achieving these targets.

Methods

Randomized, prospective, open-labeled study of 24 weeks includes stable patients on HD >3 months, age >18 years, and on Eprex for >3 months. Patients were randomized into two groups: A-(Aranesp group):HD patients on Eprex Q TIW or BIW were converted to Aranesp Q weekly, by using the conversion factor of 200:1 and those on Eprex Q weekly to Aranesp Q 2 weeks; B-(Eprex group):patients continued on Eprex treatment. Hemoglobin target was set at (105–125 g/l). Primary end points were percentage of patients achieving target Hb, hemoglobin variability, and number of dose changes in each group.

Results

This study consisted of 139 HD patients: 72 in the Aranesp and 67 in the Eprex—mean (SD) age 54 (16.2) years, 77 (55 %) males. About 46 % were diabetic. Target Hb achieved in 64.8 % of the Aranesp and 59.7 % in the Eprex (p = 0.006). Hb variability was less frequent in the Aranesp group (p = 0.2). Mean number of dose changes was 1.3 (0.87) in the Aranesp and 1.9 (1.2) in the Eprex (p < 0.001). There was 1 vascular access thrombosis in the Aranesp and 8 in the Eprex (p < 0.001). There was no difference in hospitalization and death number between the 2 groups.

Conclusions

Aranesp Q weekly or every 2 weeks is more efficient in achieving target Hb, with less dose changes and minor vascular access complications.     

Autophagy: An adaptive metabolic response to stress shaping the antitumor immunity

Several environmental-associated stress conditions, including hypoxia, starvation, oxidative stress, fast growth and cell death suppression, modulate both cellular metabolism and autophagy to enable cancer cells to rapidly adapt to environmental stressors, maintain proliferation and evade therapies. It is now widely accepted that autophagy is essential to support cancer cell growth and metabolism and that metabolic reprogramming in cancer can also favor autophagy induction. Therefore, this complex interplay between autophagy and tumor cell metabolism will provide unique opportunities to identify new therapeutic targets. As the regulation of the autophagic activity is related to metabolism, it is important to elucidate the exact molecular mechanism which drives it and the functional consequence of its activation in the context of cancer therapy. In this review, we will summarize the role of autophagy in shaping the cellular response to an abnormal tumor microenvironment and discuss some recent results on the molecular mechanism by which autophagy plays such a role in the context of the anti-tumor immune response. We will also describe how autophagy activation can behave as a double-edged sword, by activating the immune response in some circumstances, and impairing the anti-tumor immunity in others. These findings imply that defining the precise context-specific role for autophagy in cancer is critical to guide autophagy-based therapeutics which are becoming key strategies to overcome tumor resistance to therapies.     

Effect of a Contrast Modulation System on Contrast Media Use and the Rate of Acute Kidney Injury After Coronary Angiography

Objectives

The aim of the AVERT (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN) trial was to test the efficacy of the AVERT system to reduce the contrast media volume (CMV) used during coronary angiographic procedures without impairing image quality and to prevent contrast-induced acute kidney injury (CI-AKI) in patients at risk for CI-AKI.

A case series of patients with poorly-tolerated arrhythmias related to a preexcitation syndrome and presenting with atypical ECG

The aim of study was to report different and unusual patterns of preexcitation syndrome (PS) noted in patients referred for studied for poorly-tolerated arrhythmias and their frequency. Electrophysiologic study (EPS) is an easy means to identify a patient with PS at risk of serious events. However the main basis for this diagnosis is the ECG which associates short PR interval and widening of QRS complex with a delta wave.     

Natural products against cancer: Review on phytochemicals from marine sources in preventing cancer

Marine natural products have as of now been acknowledged as the most important source of bioactive substances and drug leads. Marine flora and fauna, such as algae, bacteria, sponges, fungi, seaweeds, corals, diatoms, ascidian etc. are important resources from oceans, accounting for more than 90% of the total oceanic biomass. They are taxonomically different with huge productive and are pharmacologically active novel chemical signatures and bid a tremendous opportunity for discovery of new anti-cancer molecules. The water bodies a rich source of potent molecules which improve existence suitability and serve as chemical shield against microbes and little or huge creatures. These molecules have exhibited a range of biological properties antioxidant, antibacterial, antitumour etc. In spite of huge resources enriched with exciting chemicals, the marine floras and faunas are largely unexplored for their anticancer properties. In recent past, numerous marine anticancer compounds have been isolated, characterized, identified and are under trials for human use. In this write up we have tried to compile about marine-derived compounds anticancer biological activities of diverse flora and fauna and their underlying mechanisms and the generous raise in these compounds examined for malignant growth treatment in the course of the most recent quite a long while.     

The Efficacy of Fludarabine,High Dose Cytosine Arabinoside with Granulocyte Colony Stimulating Factor (FLAG) Protocol as Salvage Therapy for Refractory/Relapsed Acute Leukemias in Adult Iraqi Patients

Refractory/relapsed acute leukemia has always been a challenging problem for hematologist. Over the past decade emphasis has been made in the development of regimens containing fludarabine, combined with cytosine arabinoside for the treatment of refractory/relapsed acute leukemias. The aim of this study is to evaluate the efficacy and toxicity of the combination of fludarabine, high dose cytarabine, and granulocyte colony stimulating factor in refractory relapsed cases of acute leukaemia, a prospective study is being conducted at the National Center of Hematology and hematology unit/Baghdad teaching hospital from July 2008 to July 2010. Twenty Patients with refractory/relapsed acute leukemia were treated with fludarabine 30 mg/m² and cytosine arabinoside (Ara-C) 2 g/m² for 5 days, and granulocyte colony stimulating factor G-CSF 300 µg/day from day 0 till neutrophil recovery (ANC > 1.0 × 10⁹/L). Response was evaluated by bone marrow examination on day 30 post chemotherapy. Patients included were refractory acute lymphoblastic leukemia (ALL) (five patients), relapsed ALL (four patients), refractory acute myeloid leukemia (AML) (eight patients), relapsed AML (three patients). Complete remission (CR) was achieved in nine (45 %) patients, while three (15 %) patients got partial remission. Three (15 %) patients died because of post chemotherapy complications and five (25 %) patient failed to achieve remission. Major complications encountered were: anemia, fever, bleeding, mucositis and bacterial infections. FLAG protocol is well tolerated and effective regimen in relapsed/refractory acute leukemias. The toxicity is acceptable, enabling most patients to receive further treatment, including transplantation procedures.