One Pot Synthesis of PEGylated Bimetallic Gold-Silver Nanoparticles for Imaging and Radiosensitization of Oral Cancers.

BACKGROUND: Radiotherapy is an important treatment modality for many types of head and neck squamous cell carcinomas. Nanomaterials comprised of high atomic number (Z) elements are novel radiosensitizers enhance radiation injury by production of free radicals and subsequent DNA damage. Gold nanoparticles are upcoming as promising radiosensitizers due to their high (Z) biocompatibility, and ease for surface engineering. Bimetallic nanoparticles have shown enhanced anticancer activity compared to monometallic nanoparticles. MATERIALS AND METHODS: PEG-coated Au-Ag alloy nanoparticles (BNPs) were synthesized using facile one pot synthesis techniques. Size of ~50±5nm measured by dynamic light scattering. Morphology, structural composition and elemental mapping were analyzed by electron microscopy and SAXS (small-angle X-ray scattering). The radiosensitization effects on KB oral cancer cells were evaluated by irradiation with 6MV X-rays on linear accelerator. Nuclear damage was imaged using confocal microscopy staining cells with Hoechst stain. Computed tomography (CT) contrast enhancement of BNPs was compared to that of the clinically used agent, Omnipaque. RESULTS: BNPs were synthesized using PEG 600 as reducing and stabilizing agent. The surface charge of well dispersed colloidal BNPs solution was -5mV. Electron microscopy reveals spherical morphology. HAADF-STEM and elemental mapping studies showed that the constituent metals were Au and Ag intermixed nanoalloy. Hydrodynamic diameter was ~50±5nm due to PEG layer and water molecules absorption. SAXS measurement confirmed BNPs size around 35nm. Raman shift of around 20 cm-1 was observed when BNPs were coated with PEG. 1H NMR showed extended involvement of - OH in synthesis. BNPs efficiently enter cytoplasm of KB cells and demonstrated potent in vitro radiosensitization with enhancement ratio ~1.5-1.7. Imaging Hoechst-stained nuclei demonstrated apoptosis in a dose-dependent manner. BNPs exhibit better CT contrast enhancement ability compared to Omnipaque. CONCLUSION: This bimetallic intermix nanoparticles could serve a dual function as radiosensitizer and CT contrast agent against oral cancers, and by extension possibly other cancers as well.

The Prevalence of Pacing-Induced Cardiomyopathy (PICM) in Patients With Long Term Right Ventricular Pacing - Is it a Matter Of Definition?

BACKGROUND: Chronic right ventricular pacing may contribute to deterioration in left ventricular ejection fraction (LVEF). The aim of the study was to identify the prevalence of pacing-induced cardiomyopathy (PICM) in patients with chronic right ventricular pacing. METHODS: Patients attending a pacemaker clinic were retrospectively identified as having had transthoracic echocardiographic LVEF measurement during the 12 months prior to device implantation. Those with cardioverter-defibrillators or biventricular devices were excluded. The remaining patients were invited back for a repeat echocardiogram. Three (3) different definitions of PICM were employed: 1) follow-up LVEF of ≤40% if baseline LVEF was ≥50%, or an absolute reduction in LVEF ≥5% if baseline LVEF was <50%; 2) follow-up LVEF of ≤40% if baseline LVEF was ≥50%, or an absolute reduction in LVEF ≥10% if baseline LVEF was ≤50%; 3) absolute reduction in LVEF ≥10% irrespective of baseline LVEF. Alternate causes of cardiomyopathy were excluded following a chart review. RESULTS: The study cohort of 118 included 67 males (mean age 77.8±10.5years) and 51 females (mean age 76.8±11.2years). The mean time between baseline and follow-up echocardiograms was 3.5+1.4years (range 1.5-6.4 years). The prevalence of PICM ranged from 5.9 to 39.0% depending on PICM definition. Multivariate analysis found that PICM was significantly associated with ventricular pacing burden (p=0.013). CONCLUSIONS: The prevalence of pacing induced cardiomyopathy is dependent on current accepted clinical definitions. A clear definition of PICM is required for a better understanding of the clinical implications of right ventricular pacing.

Surface 12 lead electrocardiogram recordings using smart phone technology.

IMPORTANCE: AliveCor ECG is an FDA approved ambulatory cardiac rhythm monitor that records a single channel (lead I) ECG rhythm strip using an iPhone. In the past few years, the use of smartphones and tablets with health related applications has significantly proliferated. OBJECTIVE: In this initial feasibility trial, we attempted to reproduce the 12 lead ECG using the bipolar arrangement of the AliveCor monitor coupled to smart phone technology. METHODS: We used the AliveCor heart monitor coupled with an iPhone cellular phone and the AliveECG application (APP) in 5 individuals. RESULTS: In our 5 individuals, recordings from both a standard 12 lead ECG and the AliveCor generated 12 lead ECG had the same interpretation. CONCLUSIONS: This study demonstrates the feasibility of creating a 12 lead ECG with a smart phone. The validity of the recordings would seem to suggest that this technology could become an important useful tool for clinical use. This new hand held smart phone 12 lead ECG recorder needs further development and validation.

Relationship between professional dental care in childhood and coronary heart disease in adulthood in a single urban dental clinic.

PURPOSE: A growing body of evidence supports an association between coronary heart disease (CHD) and dental diseases, particularly periodontitis (PD). The present study was designed to assess the relationship between childhood dental care and adult CHD in a single community dental clinic. MATERIALS AND METHODS: Consecutive patients (n = 223) at a single urban U.S. dental clinic were asked to complete a questionnaire regarding the details of their childhood and present dental care as well as CHD and PD diagnoses. RESULTS: A significantly greater proportion of patients who reported a lack of prophylactic dental care in childhood also reported a present diagnosis of CHD (54.2% vs 23.6%, P < 0.001). In a multivariate logistic regression model including the traditional CHD risk factors of smoking, family history, age and sex, the relationship between dental care in childhood and reduced CHD remained significant (OR = 0.318, 95% CI = 0.159-0.635, P = 0.001). This association cannot be explained wholly by a mechanism involving the development of PD in patients with poor childhood dental care, as PD was not significantly associated with CHD in the multivariate model (OR = 1.646, 95% CI = 0.836-3.239, P = 0.149). CONCLUSIONS: In our single dental clinic assessment, adequate childhood professional dental prophylactic care was associated with reduced CHD in adulthood, an association independent of traditional risk factors. Further studies are required to better define the magnitude of this association.

Value of coronary computed tomography as a prognostic tool.

Coronary computed tomography angiography (CCTA) has become an important part of our armamentarium for noninvasive diagnosis of coronary artery disease (CAD). Emerging technologies have produced lower radiation dose, improved spatial and temporal resolution, as well as information about coronary physiology. Although the prognostic role of coronary artery calcium scoring is known, similar evidence for CCTA has only recently emerged. Initial, small studies in various patient populations have indicated that CCTA-identified CAD may have a prognostic value. These findings were confirmed in a recent analysis of the international, prospective Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter (CONFIRM) registry. An incremental increase in mortality was found with a worse severity of CAD on a per-patient, per-vessel, and per-segment basis. In addition, age-, sex-, and ethnicity-based differences in mortality were also found. Whether changing our management algorithms based on these findings will affect outcomes is unclear. Large prospective studies utilizing targeted management strategies for obstructive and nonobstructive CAD are required to incorporate these recent findings into our daily practice.

Dabigatran: a new chapter in anticoagulation.

For the last 60 years warfarin has been the cornerstone for chronic anticoagulation in prevention of ischemic strokes and systemic embolization. Warfarin therapy has several limitations including frequent monitoring and various food and significant drug interactions, which make it a less than ideal chronic oral anticoagulant. The continued search for safe, effective, medications with predictable pharmacokinetic profiles has led to newer alternatives. Dabigatran is a potent reversible, competitive direct thrombin inhibitor which is available as the prodrug, Dabigatran etexilate. It was first approved in Europe and recently in October 2010, the US food and drug administration (FDA) has approved the use of this novel oral anticoagulation for prevention of stroke in those with non valvular atrial fibrillation. This review will cover the chemical structure, mechanism of action, pharmacokinetic profile, clinical trials, dosage, clinical implication and adverse effects of dabigatran.

Ménétrier disease in an acquired immunodeficiency syndrome patient.

Ménétrier disease is a rare disorder of unknown etiology. An overexpression of TGF-alpha has been proposed to play a role in the pathophysiology. HIV-1 tat gene product has been shown to stimulate TGF-alpha production leading to a positive feedback autocrine loop. The case of a 41-year-old male with AIDS who presented with weight loss, abdominal pain, ascites, edema, nausea, vomiting, and diarrhea is discussed. A computed tomography (CT) scan of the abdomen showed avid enhancement of the stomach mucosa. Magnetic resonance angiography revealed gastric and small bowel distention with diffuse wall thickening. Biopsies of the stomach showed marked foveolar hyperplasia with active inflammation and gland changes consistent with Ménétrier disease.