Catheter Ablation of Inducible Atrial Flutter, in Combination with Atrial Pacing and Antiarrhythmic Drugs (“Hybrid Therapy”) Improves Rhythm Control in Patients with Refractory Atrial Fibrillation

Atrial flutter or tachycardia may coexist with atrial fibrillation [AF] and can be treated with ablation techniques in attempt to reduce the total AF burden. The role of ablation of latent atrial tachyarrhythmias elicited at electrophysiologic study in conjunction with atrial pacing and antiarrhythmic drugs in patients with refractory AF has not been evaluated. We evaluated the efficacy of catheter ablation of electrically induced atrial flutter or atrial tachycardia in improving rhythm control in patients with refractory AF. Methods: Consecutive patients with refractory AF, and spontaneous atrial flutter (Group 1) or without spontaneous atrial flutter (Group 2) underwent programmed stimulation in a baseline drug-free state. All patients had electrically induced atrial flutter or tachycardia. Radiofrequency ablation of the arrhythmia substrate was performed in all patients. Primary endpoints evaluated for patient outcome in both groups included maintenance of rhythm control and freedom from recurrent atrial tachyarrhythmias. Results: Forty-three patients, with a mean age of 66±13 years were studied. Group 1 consisted of 22 patients while Group 2 had 21 patients. Ablation of the tricuspid valve-inferior venacaval isthmus was performed in 41 patients who had common atrial flutter induced at electrophysiologic study. Ablation of other atrial sites was performed in 8 patients with induced atypical flutter and 4 patients with induced atrial tachycardia. Ten of these patients had ablation of more than one arrhythmia. 17 patients (40%) had atrial pacing instituted and 28 patients remained on a class 1/3 antiarrhythmic drug. During a mean follow-up of 26±14 months, 33 patients (82.5%) remained in rhythm control. Actuarial analysis showed 96% of patients in rhythm control at 6 months, 94% at 12 months, and 90% at 24 months. Freedom from symptomatic AF recurrence was 64% at 6 months, 58% at 12 months, and 42% at 24 months. The outcome for both of these endpoints was similar for Group 1 and Group 2 (p = NS). The AF free interval increased significantly from 7±9 days to 172±121 days (p < 0.01) after ablation. This increase was again similar in both the groups. In the 14 patients were who did not receive atrial pacing and who remained on the same class 1/3 antiarrhythmic drug, the AF free interval increased from 18±17 days to 212±102 days (p < 0.01). Conclusions: We conclude that electrophysiologic studies can elicit latent atrial flutter or tachycardia in patients with refractory AF without spontaneous monomorphic atrial tachyarrhythmias. Catheter ablation of electrically induced atrial flutter or tachycardia either alone, or with atrial pacing and with antiarrhythmic drug may improve rhythm control and reduce AF recurrences. This is similar in patients with and without spontaneous atrial flutter and refractory AF.     

Similarities in cyclic vomiting syndrome across age groups

OBJECTIVE: Cyclic vomiting syndrome is well recognized in children yet has poorly defined pathogenesis and treatment. Cyclic vomiting syndrome is occasionally diagnosed in older subjects, but little attempt has been made to determine if such cases represent a unique disorder. METHODS: We reviewed clinical data from 39 patients aged 1.8-75 yr with cyclic vomiting syndrome meeting published criteria for diagnosis. Clinical characteristics were compared between subjects with symptom onset in childhood (<12 yr, n = 18) and subjects with onset at an older age (> or =12 yr, n = 21; mean age at onset 34.8+/-3.8 yr). RESULTS: All patients had stereotypical episodes of vomiting separated by varying symptom-free intervals. The prevalence rates of prodromal symptoms, triggering events, alleviants, associated symptoms including abdominal pain and diarrhea, and past or family history of migraine were similar in the children and older subjects with the syndrome (p > 0.3 for each). Delay in diagnosis was greater in the older subset (3.1+/-0.8 yr vs 7.9+/-3.1 yr, p < 0.05). Interepisode intervals and total number of hospitalizations did not differ significantly between younger and older patients, but duration of episodes was significantly longer in the older group (2.0+/-0.5 days vs 3.8+/-0.4 days, p < 0.01). When subjects were further substratified by age of illness onset, duration of episodes progressively increased from infant/toddlers (1.8+/-0.4 days) through childhood (2.3+/-0.5 days) and adolescence (2.9+/-1.0 days) and into adulthood (3.9+/-0.5; p < 0.05 across groups). Episode duration did not lengthen further in subgroups >20 yr of age. CONCLUSIONS: Many characteristics of cyclic vomiting syndrome are similar irrespective of age at disorder onset, suggesting a uniform pathogenesis. Duration of episodes increases with age to age 20 yr. Increased awareness of the condition and a high index of suspicion may help decrease delay in diagnosis after symptom onset.     

Utilization of Anthocyanins-Rich Extract from Banana Bract in the Green Synthesis of AgNPs with Anti-proliferative Potential

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Present study was undertaken to optimize the extraction conditions for the recovery of anthocyanins from an...     

Association of TNF level with production of circulating cellular microparticles during clinical manifestation of human cerebral malaria

Microparticles (MPs) resulting from vesiculation of different cell types in Plasmodium falciparum infection correlate with the level of proinflammatory cytokine TNF that may thereby determine the disease severity. Using TruCount tube based flow cytometric method for the exact quantification of MP and enzyme linked immunosorbent assay for the measurement of TNF, we conducted a hospital based case control study on P. falciparum malaria patients to scrutinize and infer the link between the two. In 52 cerebral malaria (CM), 21 multi-organ-dysfunction (MOD), 12 non cerebral severe malaria (NCSM) and 43 uncomplicated malaria patients, the MP level was found to be significantly elevated in febrile malaria patients compared to healthy controls and a striking decrease in MP level was observed with the clearance of the P. falciparum infection in the patients upon follow-up. The lowering of the parasite density with the level of plasma TNF and the positive correlation of the cytokine with the cell derived MPs and negative correlation with the respective cell count in human malaria patients suggests that TNF may be a key stimulant to the cells resulting in the release of MPs in malaria infection.     

Conjugating doxorubicin to polymannose: a new strategy for target specific delivery to lung cancer cells

Abstract

As mannose receptors are known to be over-expressed in cancer cells, we synthesized polymannose-doxorubicin (PM-DOX) conjugates with the objective of targeting the drug to cancer cells. DOX was conjugated to oxidized PM through Schiff’s linkages to obtain PM-DOX conjugates. In order to examine the superior targeting efficacy of PM-DOX conjugate, sodium alginate (SA) was conjugated to DOX by similar chemistry and compared with PM-DOX conjugate. The cytotoxicity of the conjugates was investigated in A549 cell lines using MTT Assay and the cell uptake and retention studies, were performed using flow cytometry and cell imaging. In vitro drug release studies with both PM-DOX and SA-DOX conjugates showed an initial burst release of DOX up to 37–39% at 1?h, followed by a steady release up to 58–62% at 24?h in human plasma while negligible release was observed in phosphate buffered saline. The conjugates exhibited negligible hemolytic potential to human erythrocytes compared to free DOX. The PM-DOX conjugate showed better cytotoxic potential against A549 cells at lower concentration (equivalent to 0.27?μg/mL of DOX) at 72?h compared to free DOX and SA-DOX conjugate. Further, PM-DOX conjugate showed enhanced uptake by the cells in comparison with SA-DOX conjugate thereby confirming the target specificity of PM to the cancer cells.     

E6-AP association promotes SOD1 aggresomes degradation and suppresses toxicity

Protein aggregation and ordered fibrillar amyloid deposition inside and outside of the central nervous system cells is the common pathologic hallmark of most aging-related neurodegenerative disorders. Dominant mutations in the gene encoding superoxide dismutase 1 (SOD1) protein are linked to familial amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by progressive degeneration of motor neurons, leading to muscle paralysis and death. The major histochemical hallmark in the remaining motor neurons of ALS is the intracellular accumulation of ubiquitinated inclusions consisting of insoluble aberrant protein aggregates. However, the molecular pathomechanisms underlying the process have been elusive. Here for the first time, we report that E6-AP, a homologous to E6-AP C terminus-type E3 ubiquitin ligase depleted in ALS mouse models before neurodegeneration. E6-AP coimmunoprecipitates with the SOD1 protein and is predominantly mislocalized in mutant SOD1-containing inclusion bodies. Overexpression of E6-AP increases the ubiquitination and facilitates degradation of SOD1 proteins. Finally, we show that the overexpression of E6-AP suppresses the aggregation and cell death mediated by mutated SOD1 proteins and cellular protective effect is more prominent when E6-AP is overexpressed along with Hsp70. These data suggest that enhancing the activity of E6-AP ubiquitin ligase might be a viable therapeutic strategy to eliminate mutant SOD1-mediated toxicity in ALS.     

Pediatric maxillofacial injuries and its management

BackgroundPediatric facial injuries are common due to children's high level of activity which gradually decreases as age advances. Main etiology in cases of pediatric age group are self-fall, sports related injuries, interpersonal violence and lastly road traffic accident. Pattern and management of facial fracture in pediatric age group is different to that of adult population.Material and methodsThis study included 87 patients who had facial injuries and who reported at dental institute RIMS, Ranchi over a period of three years from 2017 to 2020. Initial assessment diagnosis and management were given to the patients.ResultsSelf-fall accounted as the leading cause of fracture (47.1%). Most frequent age group with facial injuries were from 7 to 12 years age group (49.1%). Dentoalveolar pattern of facial fracture was most common accounting for (39.1%) followed by mandible fracture in 33.3%. Closed reduction of the fracture was the most common way of treatment. Open reduction and fixation was carried out in 3.4% patients.ConclusionSelf-fall was the main etiology in our study and younger age group patients were more involved. Conservative treatment are generally given to pediatric age group, with open reduction in few cases on the basis of displacement. Close monitoring and follow up is mandatory in these age group.