Echocardiography for Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy. The prevalence of phenotypic expression, in the absence of another systemic or cardiac disease causing increased left ventricular (LV) wall thickness, is estimated to be 1:500. The frequency of clinical presentation is far less, highlighting the need for a non-invasive diagnostic imaging tool. Echocardiography is readily available and allows for structural characterization and hemodynamic assessment of the hypertrophic heart and to screen patients at-risk for HCM, such as first degree relatives of affected individuals, and differentiate HCM from the athletic heart. Echocardiography can also be used to assess for anatomic abnormalities of the mitral valve apparatus that may exacerbate LV outflow track obstruction and to further risk stratify patients during exercise. Finally, echocardiography plays an integral role in guiding alcohol septal ablation procedures.     

New method of thrombus preparation using a fluid model for evaluation of thrombectomy devices in a swine model

Background

Mechanical thrombectomy is a promising new modality of interventional stroke treatment. Preparation of thrombus is a very important step for the evaluation of the mechanical thrombectomy devices. The objective of this study was to explore a new method of thrombus preparation with fluid model (FM) for assessment of thrombectomy devices used in the recanalization of acute ischemic stroke.

Methods

Elongation test and catheter injection test were used to evaluate the mechanical properties of thrombi prepared by FM and static model (SM). Histological structures of two artificial clots and specimens of stroke patients were compared. Radiopacity of thrombus made by FM was evaluated in a swine embolization model.

Results

The maximum tensile length of thrombi prepared by FM and SM were significantly higher (4.28 ± 0.23 cm vs 3.16 ± 0.13 cm, P < 0.01) and showed less breakage on catheter injection test (13% vs 60%, P < 0.05). Histological features of thrombi prepared by FM showed mixed thrombus structure, similar to thromboemboli retrieved from acute stroke patients, while clots generated by SM were replete with erythrocytes. A total of twelve vessels in two swine were successfully occluded (TIMI 0 or 1), with sufficient radiopacity of each injected thrombus.

Conclusion

The thrombus prepared by FM had good mechanical stability, sufficient radiopacity, and similar histological structure of thromboemboli retrieved from stroke patients, which make it possible to be used in the evaluation of thrombectomy devices.     

Survival after burn in a sub-Saharan burn unit: Challenges and opportunities

Background

Burns are among the most devastating of all injuries and a major global public health crisis, particularly in sub-Saharan Africa. In developed countries, aggressive management of burns continues to lower overall mortality and increase lethal total body surface area (TBSA) at which 50% of patients die (LA50). However, lack of resources and inadequate infrastructure significantly impede such improvements in developing countries.

Methods

This study is a retrospective analysis of patients admitted to the burn center at Kamuzu Central Hospital in Lilongwe, Malawi between June 2011 and December 2012. We collected information including patient age, gender, date of admission, mechanism of injury, time to presentation to hospital, total body surface area (TBSA) burn, comorbidities, date and type of operative procedures, date of discharge, length of hospital stay, and survival. We then performed bivariate analysis and logistic regression to identify characteristics associated with increased mortality.

Results

A total of 454 patients were admitted during the study period with a median age of 4 years (range 0.5 months to 79 years). Of these patients, 53% were male. The overall mean TBSA was 18.5%, and average TBSA increased with age—17% for 0–18 year olds, 24% for 19–60 year olds, and 41% for patients over 60 years old. Scald and flame burns were the commonest mechanisms, 52% and 41% respectively, and flame burns were associated with higher mortality. Overall survival in this population was 82%; however survival reduced with increasing age categories (84% in patients 0–18 years old, 79% in patients 19–60 years old, and 36% in patients older than 60 years). TBSA remained the strongest predictor of mortality after adjusting for age and mechanism of burn. The LA50 for this population was 39% TBSA.

Discussion

Our data reiterate that burn in Malawi is largely a pediatric disease and that the high burn mortality and relatively low LA50 have modestly improved over the past two decades. The lack of financial resources, health care personnel, and necessary infrastructure will continue to pose a significant challenge in this developing nation. Efforts to increase burn education and prevention in addition to improvement of burn care delivery are imperative.     

Dibucaine in Ionic-Gradient Liposomes: Biophysical,Toxicological, and Activity Characterization

Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the injection site, limiting the time of anesthesia. One approach to prolong analgesia is to entrap local anesthetic agents in nanostructured carriers (e.g., liposomes). Here, we report that using an ammonium sulphate gradient was the best strategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scattering and nanotracking analyses were used to characterize vesicle properties, such as, size, polydispersity, zeta potentials, and number. In vitro kinetic experiments revealed the sustained release of DBC (50% in 7 h) from the liposomes. In addition, in vitro (3T3 cells in culture) and in vivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBC cyto/cardiotoxicity and morphological changes in zebrafish larvae. Moreover, the anesthesia time attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) than that with free DBC (11 h), at 320 μM (0.012%), confirming it as a promising long-acting liposome formulation for parenteral drug administration of DBC.     

Investigating phase separation in amorphous solid dispersions via Raman mapping

The bioavailability of poorly-water-soluble active pharmaceutical ingredients (APIs) can be significantly improved by so-called amorphous solid dispersions (ASDs). However, the long-term stability of ASDs might be impaired by API recrystallization and/or amorphous phase separation (APS). So far, no methods have been reported to quantify APS in ASDs. In this work, phase-separation kinetics as well as the compositions of the two amorphous phases evolving due to APS were quantitatively determined for the first time using confocal Raman spectroscopy. Raman spectra were evaluated via non-linear multivariate Indirect Hard Modeling and verified by differential scanning calorimetry and hot-stage microscopy. APS in water-free ASDs of ibuprofen and poly (DL-lactic-co-glycolic acid) was investigated considering the influence of temperature and polymer architecture (linear vs. star-shaped). Water absorbed at 40?°C and 75% relative humidity (RH) promotes APS which was quantified for formulations of felodipine/poly(vinyl pyrrolidone) and ibuprofen/poly(vinyl pyrrolidone).     

Penta-block copolymer microspheres: Impact of polymer characteristics and process parameters on protein release

Here, we aimed to develop protein loaded microspheres (MSs) using penta-block PLGA-based copolymers to obtain sustained and complete protein release. We varied MS morphology and studied the control of protein release. Lysozyme was used as a model protein and MSs were prepared using the solid-in-oil-in-water emulsion solvent extraction method. We synthesized and studied various penta-block PLGA-based copolymers. Copolymer characteristics (LA/GA ratio and molecular weight of PLGA blocks) influenced MS morphology. MS porosity was influenced by process parameters (such as solvent type, polymer concentration, emulsifying speed), whereas the aqueous volume for extraction and stabilizer did not have a significant effect. MSs of the same size, but different morphologies, exhibited different protein release behavior, with porous structures being essential for the continuous and complete release of encapsulated protein. These findings suggest strategies to engineer the morphology of MSs produced from PLGA-based multi-block copolymers to achieve appropriate release rates for a protein delivery system.     

Lipid based nanocarriers: a translational perspective

Over the recent couple of decades, pharmaceutical field has embarked most phenomenal noteworthy achievements in the field of medications as well as drug delivery. The rise of Nanotechnology in this field has reformed the existing drug delivery for targeting, diagnostic, remedial applications and patient monitoring. The convincing usage of nanotechnology in the conveyance of medications that prompts an extension of novel lipid-based nanocarriers and non-liposomal systems has been discussed. Present review deals with the late advances and updates in lipidic nanocarriers, their formulation strategies, challenging aspects, stability profile, clinical applications alongside commercially available products and products under clinical trials. This exploration may give a complete idea viewing the lipid based nanocarriers as a promising choice for the formulation of pharmaceutical products, the challenges looked by the translational process of lipid-based nanocarriers and the combating methodologies to guarantee the headway of these nanocarriers from bench to bedside.     

An overview of monitoring and supplementation of omega 3 fatty acids in cystic fibrosis

Essential fatty acid deficiency has been increasingly reported in patients with cystic fibrosis. The purpose of this work is to critically summarize previous data on fatty acid status and ω3 supplementation in cystic fibrosis. Although the reported abnormalities differ from study to study, the two most consistent features appeared to be reduced circulating levels of linoleic acid and docosahexaenoic acid (DHA). On the assumption that the fatty acid composition of erythrocyte cell membranes may be similar to that of other organs, it seems appropriate to monitor the phospholipid profile from erythrocyte membranes together with circulating blood levels. Formulations containing widely variable DHA doses, ranging from 300 mg to 5 g per day, have been administered to patients with cystic fibrosis with discrepant outcomes. Randomized controlled trials are needed in order to draw firm conclusions on the therapeutic effect of ω3 fatty acid supplementation in cystic fibrosis.