Probe angioplasty through an intracoronary probing catheter in lesions which are difficult to cross

The clinical records of the first 17 consecutive patients (20 lesions) in whom percutaneous transluminal coronary angioplasty was done using the ultra-low profile "balloon-on-wire probe" passed through an intracoronary probing catheter were reviewed. All patients had high-grade "difficult" lesions. In 15 lesions (12 patients) other balloon systems (over-the-wire low profile balloons (n = 9), and balloon-on-wire used alone, (n = 6)) had failed to cross the lesion. Acute ischemia due to complete occlusion at the site of the lesion during attempts to cross was seen in 3 of these patients. The intracoronary probing catheter was used to deliver the probe across the lesion in all these cases. Successful dilatation was achieved in 14 lesions (93%). In 5 lesions (5 patients) this combination was used as the initial strategy. Three of these had chronic total occlusions. Successful dilatation was achieved in 3 lesions (60%) using this combination and in 1 lesion over-the-wire balloon finally succeeded. There was 1 failure. The intracoronary probing catheter in combination with probe balloon wire offers a promising method to increase the success rate in patients with high grade "difficult" lesions. This combination is especially useful in situations where other balloon systems fail to cross the lesion.     

Stable Fixation of Short-stem Femoral Implants in Patients 70 Years and Older

Background  

Limitations of conventional uncemented femoral stems persist, including proximal-distal mismatch, nonideal load transfer, loss of bone, and difficulties with minimally invasive surgery. Metaphyseal-engaging short-stem implants have been designed to address these issues in THA. While these devices have been studied in younger patients, it is unclear whether they offer advantages in older patients.     

Performance assessment of Acute Physiology and Chronic Health Evaluation II and Simplified Acute Physiology Score II in a referral respiratory intensive care unit in Iran

Background/purposeNowadays, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) scoring systems have drawn much attention for the evaluation and prediction of disease process in patients admitted to intensive care units (ICUs). To use these scoring tools, their predicting power must be initially validated for the target patients. This study was conducted to evaluate the performance of these two scoring systems in an ICU for respiratory diseases in Iran.Material and methodsAll records of patients admitted during a 1-year period were retrospectively reviewed, and the APACHE II and SAPS II scores were calculated accordingly. Information gathering was performed using a questionnaire.ResultsA total of 415 records were used. The mean age of patients was 49.28 ± 0.94 years. Using receiver operating-characteristic curve, cutoff points for 80% sensitivity and specificity of mortality prediction for APACHE and SAPS scores were 13.5 and 27.5, respectively. Calibration and discrimination studies indicated an acceptable status for both scales, but APACHE II scoring system seemed to show rewarding outcomes.ConclusionResults indicate that APACHE II scoring system can be considered as a reliable method for predicting mortality in our referral respiratory ICU.     

Etoposide loaded solid lipid nanoparticles for curtailing B16F10 melanoma colonization in lung

Poor solubility of etoposide and associated poor bioavailability of the drug was circumvented by developing solid lipid nanocarrier system. The objective of the research work was to prepare etoposide loaded solid lipid nanoparticles (SLN) for improved efficacy and therapy of metastasized cancers. Entrapment of drug into nanoparticulate system modifies the pharmacokinetic and biodistribution profile of the drug with improved therapeutic efficacy. Solid lipid nanoparticles of various triglycerides were prepared using hot homogenization technique. Further, the process and formulation parameters viz. homogenization cycle and pressure, type of lipid were optimized. Developed nanoparticles were characterised for particle size, in vitro dissolution studies, DSC thermogram, surface morphology and cytotoxicity assay. Pharmacokinetic and biodistribution study were performed to assess the distribution of the drug in vivo. Modulation of the therapeutic activity of the drug was studied by performing antimetastatic activity on a B16F10 melanoma mouse model. The obtained results exhibited suitability of trimysristin for fabrication of nanoparticles. Characterisation of nanoparticles depicted formation of homogenous, spherical particles entrapping approximately 50% of the drug. The results for the performed MTT assay suggested that the developed nanoparticles exhibited cytotoxicity in a time- and concentration-dependent fashion. These findings concord with the results of the in vitro dissolution profile. Pharmacokinetic parameters demonstrated increase in area under curve (AUC), t_1/2 and mean residence time (MRT) for drug in plasma. Further there is enhancement in the ratio of the drug that reaches to the highly perfused organs (upon encapsulation into solid lipid nanoparticles). Generally, cancer cells metastasized through the blood or lymphatic system. Accumulation of the drug in the highly perfused organ suggests suitability of the developed nanoparticles for targeting metastasized tumors. This was proved by the findings of the in vivo B16F10 mouse melanoma model. Improvement in the tumoricidal activity and survival rate of the animals substantiates the application of nanoparticles for improved therapeutic activity of etoposide.     

An insight into transcatheter aortic valve implantation—a perspective from multidetector‐computed tomography

Transcatheter aortic valve implantation (TAVI) has now become an acceptable alternative to surgical aortic valve replacement for patients with severe aortic stenosis at high risk. The early enthusiasm for this technology has not diminished but rather has developed at an unprecedented rate over the last decade. Alongside the developments in implantation technique, transcatheter design, and postprocedural care, cardiac imaging modalities have also had to concurrently evolve to meet the perpetual demand for lower peri‐ and postprocedural complication rates. Although transthoracic and transesophageal echocardiography remain vital in patient's selection and periprocedural guidance, there is now emerging evidence that indicates that multidetector‐computed tomography (MDCT) may also have an equally important role to play. The aim of the current review is to examine the modern role of MDCT in assessing patients with aortic stenosis being considered for TAVI. © 2012 Wiley Periodicals, Inc.     

Comparative Activities of Telavancin Combined with Nafcillin,Imipenem, and Gentamicin against Staphylococcus aureus

Beta-lactams enhance the killing activity of vancomycin. Due to structural and mechanistic similarities between vancomycin and telavancin, we investigated the activity of telavancin combined with nafcillin and imipenem compared to the known synergistic combination of telavancin and gentamicin. Thirty strains of Staphylococcus aureus, 10 methicillin-susceptible S. aureus (MSSA), 10 methicillin-resistant S. aureus (MRSA), and 10 heterogeneously vancomycin-intermediate S. aureus (hVISA), were tested for synergy by time-kill methodology. Six strains (2 each of MSSA, MRSA, and hVISA) were further evaluated in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model with simulated regimens of 10 mg/kg of body weight of telavancin once daily alone and combined with 2 g nafcillin every 4 h, 500 mg imipenem every 6 h, or 5 mg/kg gentamicin once daily over 72 h. In the synergy test, 67% of strains displayed synergy with the combination of telavancin and gentamicin, 70% with telavancin and nafcillin, and 63% with telavancin and imipenem. In the PK/PD model, the activities of all three combinations against MRSA and hVISA were superior to all individual drugs alone (P ≤ 0.002) and were similar to each other (P ≥ 0.187). The activities of all three combinations against MSSA were generally similar to each other except for one strain where the combination of telavancin and imipenem was superior to all other regimens (P ≤ 0.011). The activity of the combination of telavancin and beta-lactam agents was similar to that of telavancin and gentamicin against S. aureus, including resistant strains. Because beta-lactam combinations are less likely to be nephrotoxic than telavancin plus gentamicin, these beta-lactam combinations may have clinical utility.     

Focal adhesion kinase a potential therapeutic target for pancreatic cancer and malignant pleural mesothelioma

The non-receptor cytoplasmic tyrosine kinase, Focal Adhesion Kinase (FAK) is known to play a key role in a variety of normal and cancer cellular functions such as survival, proliferation, migration and invasion. It is highly active and overexpressed in various cancers including Pancreatic Ductal Adenocarcinoma (PDAC) and Malignant Pleural Mesothelioma (MPM). Here, initially, we demonstrate that FAK is overexpressed in both PDAC and MPM cell lines. Then we analyze effects of two small molecule inhibitors PF-573228, and PF-431396, which are dual specificity inhibitors of FAK and proline rich tyrosine kinase 2 (PYK2), as well as VS-6063, another small molecule inhibitor that specifically inhibits FAK but not PYK2 for cell growth, motility and invasion of PDAC and MPM cell lines. Treatment with PF-573228, PF-431396 and VS-6063 cells resulted in a dose-dependent inhibition of growth and anchorage-independent colony formation in both cancer cell lines. Furthermore, these compounds suppressed the phosphorylation of FAK at its active site, Y397, and functionally induced significant apoptosis and cell cycle arrest in both cell lines. Using the ECIS (Electric cell-substrate impedance sensing) system, we found that treatment of both PF compounds suppressed adherence and migration of PDAC cells on fibronectin. Interestingly, 3D-tumor organoids derived from autochthonous KC (Kras;PdxCre) mice treated with PF-573228 revealed a significant decrease in tumor organoid size and increase in organoid cell death. Taken together, our results show that FAK is an important target for mesothelioma and pancreatic cancer therapy that merit further translational studies.     

Adaptive optics imaging of the retina

Adaptive optics is a relatively new tool that is available to ophthalmologists for study of cellular level details. In addition to the axial resolution provided by the spectral-domain optical coherence tomography, adaptive optics provides an excellent lateral resolution, enabling visualization of the photoreceptors, blood vessels and details of the optic nerve head. We attempt a mini review of the current role of adaptive optics in retinal imaging. PubMed search was performed with key words Adaptive optics OR Retina OR Retinal imaging. Conference abstracts were searched from the Association for Research in Vision and Ophthalmology (ARVO) and American Academy of Ophthalmology (AAO) meetings. In total, 261 relevant publications and 389 conference abstracts were identified.