Incremental value of live/real time three-dimensional transesophageal echocardiography over the two-dimensional technique in the assessment of aortic aneurysm and dissection

We compared findings from intraoperative live/real time three-dimensional transesophageal echocardiography (3DTEE) and two-dimensional transesophageal echocardiography (2DTEE) with surgery in 67 patients having aortic aneurysm and/or aortic dissection. Of these, 20 patients had aortic aneurysm without dissection, 21 aortic aneurysm and dissection, and 26 aortic dissection without aneurysm. 3DTEE diagnosed the type and location of aneurysm correctly in all patients unlike 2DTEE, which missed an aneurysm in one case. There were four cases of aortic aneurysm rupture. Three of them were diagnosed by 3DTEE but only one by 2DTEE, and one missed by both techniques. The mouth of saccular aneurysm, site of aortic aneurysm rupture, and communication sites between perfusing and nonperfusing lumens of aortic dissection could be viewed en face only with 3DTEE, enabling comprehensive measurements of their area and dimensions as well as increasing the confidence level of their diagnosis. In all patients with aortic dissection, 3DTEE enabled a more confident diagnosis of dissection because the dissection flap when viewed en face presented as a sheet of tissue rather than a linear echo seen on 2DTEE which can be confused with an artifact. 2DTEE missed dissection in one patient. In six cases the dissection flap involved the right coronary artery orifice by 3DTEE and surgery. These were missed by 2DTEE. Aortic regurgitation severity was more comprehensively assessed by 3DTEE than 2DTEE. Aneurysm size by 3DTEE correlated well with 2DTEE and surgery/computed tomography scan. In conclusion, 3DTEE provides incremental information over 2DTEE in patients with aortic aneurysm and dissection.     

Atrial Myxoma-Related to Chronic Immunosuppression: A case report

Although rare, atrial myxoma is the most common primary tumour of the heart. Its relation to immunosuppression in solid organ transplant is presently debateable. We report the case of a 71-year-old male patient who underwent renal transplant 17 years prior. Since that time he continued high dose immunosuppression without physician consultation and presented to us with atrial myxoma and its complications raising the question of any association between immunosuppression and the development of atrial myxoma.     

Blood conservation strategies in orthopedic surgeries: A review

In orthopedics management of surgical blood loss is an important aspect which has evolved along with modern surgeries. Replacement of lost blood by transfusion alone is not the answer as was considered earlier. Complications like infection and immune reaction due to blood transfusion are a major concern. Today numerous techniques are available in place of allogenic blood transfusion which can be employed safely and effectively. In this article we have reviewed these techniques, their merits and demerits.     

Ethical Considerations in Conducting Research on Autism Spectrum Disorders in Low and Middle Income Countries

Autism spectrum disorder (ASD) is being identified in an ever-increasing number of countries, including many that are low or middle income (LMIC). Research conducted in these countries requires awareness of unique ethical issues. Drawing on the experience of two organizations that have been involved in conducting and collaborating in ASD research in India, we describe specific considerations in conducting epidemiological, genetic and treatment studies as well as general principles from the field of multinational clinical research as they apply to the conduct of ASD research. We argue that greater attention to ethical concerns will result in quality studies conducted in LMICs that are also of greatest relevance for families and children with ASD.     

β‐amyloid and ATP‐induced diffusional trapping of astrocyte and neuronal metabotropic glutamate type‐5 receptors

β‐Amyloid (Aβ) oligomers initiate synaptotoxicity following their interaction with the plasma membrane. Several proteins including metabotropic glutamate type 5 receptors (mGluR5s) contribute to this process. We observed an overexpression of mGluR5s in reactive astrocytes surrounding Aβ plaques in brain sections from an Alzheimer's disease mouse model. In a simplified cell culture system, using immunocytochemistry and single molecule imaging, we demonstrated a rapid binding of Aβ oligomers on the plasma membrane of astrocytes. The resulting aggregates of Aβ oligomers led to the diffusional trapping and clustering of mGluR5s. Further, Aβ oligomers induced an increase in ATP release following activation of astroglial mGluR5s by its agonist. ATP slowed mGluR5s diffusion in astrocytes as well as in neurons co‐cultured with astrocytes. This effect, which is purinergic receptor‐dependent, was not observed in pure neuronal cultures. Thus, Aβ oligomer‐ and mGluR5‐dependent ATP release by astrocytes may contribute to the overall deleterious effect of mGluR5s in Alzheimer's disease. GLIA 2013;61:1673–1686     

Vitamin D supplementation for treatment and prevention of pneumonia in under-five children: <Emphasis Type="Italic">A randomized double-blind placebo controlled trial</Emphasis>

Objective

To evaluate the efficacy of single oral mega-dose of Vitamin D3 for treatment and prevention of pneumonia in underfive children.

Design

Randomized, double blind, placebo-controlled trial.

Setting

Tertiary-care hospital.

Participants

324 children (of 980 assessed) between 6 mo-5 y age (median (IQR): 12 (7,19.8) mo) with WHO-defined severe pneumonia. Of these, 126 (39%) were vitamin D deficient (serum 25(OH)D <12 ng/mL).

Intervention

100,000 IU of oral cholecalciferol (n= 162) or placebo (n= 162) in single dose, administered at enrolment.

Outcome variables

Primary: Time to resolution of severe pneumonia and proportion of children having recurrence of pneumonia in next 6 months; Secondary: Change in serum levels of 25(OH)D; immunoglobulins IgA, IgG, IgM, and cathelicidin 2 weeks following supplementation; and time taken for overall resolution of illness.

Results

Median (95% CI) time for resolution of severe pneumonia was 30 (29, 31) h in the vitamin D group as compared to 31 (29,33) h in the placebo group [adjusted hazard ratio (95% CI): 1·39 (1·11, 1·76); P=0·005]. The risk of recurrence of pneumonia in next 6 months was comparable in the two groups [placebo: 36/158 (22·8%); vitamin D: 39/156 (25%); RR (95% CI): 1·13 (0·67,1·90); P=0·69]. Proportion of vitamin D deficient children declined from 38% to 4% in the supplementation group, and from 41% to 33% in the placebo group, two weeks after supplementation. There was no significant effect of vitamin D supplementation on serum levels of cathelicidin, IgA and IgG. The time taken for complete recovery from pneumonia, duration of hospitalization, and fever clearance time were comparable for the two groups. No adverse event was noted related to the intervention.

Conclusion

There is no robust evidence of a definite biological benefit, either for therapy or prevention, to suggest a routine megadose supplement of vitamin D3 for under-five children with severe pneumonia.

     

Microemulsion-based delivery of triamcinolone acetonide to posterior segment of eye using chitosan and butter oil as permeation enhancer: an in vitro and in vivo investigation

The aim of the study was to formulate a microemulsion (ME) using chitosan (CH) and the butter oil (BO) as a permeation enhancer for targeting drug to the posterior segment of the eye, via topical route. Triamcinolone acetonide (TA) was selected as the model drug since it undergoes extensive first-pass metabolism, leading to poor oral bioavailability of 23%. For optimisation of BO concentration, different ratios of TA:BO were prepared by simple physical mixing in the ratio of 1:9 to 9:1 and diffusion study was performed. MEs containing TA, TA:BO and TA CH ME were formulated by water titration method. Globule sizes of TA ME, TA:BO ME and TA CH ME were found to be 66.06?±?0.32?nm, 78.52?±?1.50?nm and 97.30?±?2.50?nm, respectively. In ex vivo diffusion studies using goats eye, TA:BO ME (31.33?±?0.46 and 33.98?±?0.23) and TA CH ME (24.10?±?0.41 and 27.00?±?0.18) showed higher percentage of drug diffusion in comparison to TA ME (13.29?±?0.41and 15.56?±?0.34) and TA solution (8.20?±?1.04 and 10.39?±?0.22) in presence and in absence of vitreous humour. Fluorescence intensity of coumarin-6 (as a marker) loaded ME with BO and CH was found to be higher, confirming their role in altering membrane permeability and facilitating coumarin-6 diffusion to the posterior chamber. Overall, it was concluded that BO enhances the bioavailability of TA across the retina, thereby proving its potential as permeation enhancer in facilitating drug delivery to the posterior segment of the eye.     

Development and Validation of Stability-indicating HPLC Method for Simultaneous Estimation of Cefixime and Linezolid

A stability-indicating reverse phase high performance liquid chromatography method was developed and validated for cefixime and linezolid. The wavelength selected for quantitation was 276 nm. The method has been validated for linearity, accuracy, precision, robustness, limit of detection and limit of quantitation. Linearity was observed in the concentration range of 2-12 μg/ml for cefixime and 6-36 μg/ml for linezolid. For RP-HPLC, the separation was achieved by Phenomenex Luna C₁₈ (250×4.6 mm) 5 μm column using phosphate buffer (pH 7):methanol (60:40 v/v) as mobile phase with flow rate 1 ml/min. The retention time of cefixime and linezolid were found to be 3.127 min and 11.986 min, respectively. During force degradation, drug product was exposed to hydrolysis (acid and base hydrolysis), H₂O₂, thermal degradation and photo degradation. The % degradation was found to be 10 to 20% for both cefixime and linezolid in the given condition. The method specifically estimates both the drugs in presence of all the degradants generated during forced degradation study. The developed methods were simple, specific and economic, which can be used for simultaneous estimation of cefixime and linezolid in tablet dosage form.