Electromagnetic navigation during flexible bronchoscopy

BACKGROUND: Flexible bronchoscopy is routinely utilized in the diagnosis and treatment of various lung diseases. Nondiagnostic bronchoscopy leads to more invasive interventions, such as transthoracic needle aspiration, mediastinoscopy or even thoracotomy. Electromagnetic navigation is a novel technology that facilitates approaching peripheral lung lesions, which are difficult to sample by conventional means. The navigation system involves creating an electromagnetic field around the chest and localizing an endoscopic tool using a microsensor overlaid upon previously acquired CT images. OBJECTIVES: To determine the practicality, accuracy and safety of real-time electromagnetic navigation, coupled with previously acquired 3D CT images, in locating artificially created peripheral lung lesions in a swine model. METHODS: Peripheral lung lesions were created in four swine models by insertion of a metal tube (1 x 10 mm) via a transthoracic approach. An electromagnetic field was created by placing the animal on an electromagnetic location board. A position sensor incorporated into the distal tip of a dedicated tool was used to navigate to the various target lesions. Information gathered in real time during bronchoscopy was presented on a monitor simultaneously by displaying previously acquired CT images. Upon reaching the target lesion, biopsies were performed and the functionality and safety of the superDimension/Bronchus System was observed and documented. RESULTS: The registration accuracy expressed by the fiducial target registration error, expressing both the registration quality and the stability of fiducial (registration) points, was 4.5 mm on average. No adverse effects, such as pneumothorax or internal bleeding, were encountered in any of the animals in this study. CONCLUSIONS: Real-time electromagnetic positioning technology coupled with previously acquired CT images is an accurate technology added to standard bronchoscopy to assist in reaching peripheral lung lesions and performing biopsies.     

Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheumatoid arthritis: data from a phase II clinical trial

OBJECTIVE: Adenosine exerts antiinflammatory effects via activation of the A3 adenosine receptor (A3AR), a Gi protein-associated cell-surface receptor, overexpressed in synovial tissue and peripheral blood mononuclear cells (PBMC) in patients with active rheumatoid arthritis (RA). CF101 is a highly specific orally bioavailable A3AR agonist. METHODS: This was a multicenter study, blinded to dose, designed to assess the clinical activity and safety of CF101 in active RA. Seventy-four patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 bid for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. A3AR expression levels were analyzed in PBMC from 18 patients. RESULTS:. Maximal responses were observed with 1.0 mg bid, lower at 0.1 and 4.0 mg bid. At 12 weeks, 55.6%, 33.3%, and 11.5% of the patients receiving 1.0 mg CF101 achieved ACR20%, 50%, and 70% responses, respectively. CF101 was generally well tolerated, with mild headache (4.1%), nausea (2.7%), and rash (2.7%) being the most common treatment-related adverse events. Statistically significant correlations between A3AR overexpression at baseline and ACR50 and ACR70 responses were observed. CONCLUSION: CF101 administered bid for 12 weeks resulted in improvement in signs and symptoms of RA that did not achieve statistical significance, and was safe and well tolerated. The expression level of A3AR was directly correlated with patient responses to CF101, suggesting its utilization as a biomarker for the pharmacodynamic and therapeutic effects of this novel agent. These findings require confirmation in a double-blind randomized placebo-controlled trial, currently under way.     

Impaired nocturnal melatonin secretion in non-dipper hypertensive patients

BACKGROUND: Melatonin plays a role in the biologic regulation of circadian rhythms, including sleep. Melatonin has also been shown to modulate vascular smooth muscle tone and to induce hemodynamic effects in humans. OBJECTIVE: To evaluate whether melatonin plays a role in the circadian rhythm of blood pressure in hypertensive patients. METHODS: Sixteen elderly patients with essential hypertension were evaluated. Patients were defined as either dippers (DIP, n = 8) or non-dippers (NDIP, n = 8) according to the nocturnal change in the mean arterial pressure (MAP). 6-Sulfatoxymelatonin (6-SMT), the main melatonin metabolite, was determined by enzyme-linked immunosorbent assay (ELISA) in two separate urine collections, one in the daytime and one during the night. RESULTS: Both groups of DIP and NDIP hypertensives were comparable in regard to age and sex. During the night, the mean arterial pressure decreased by 10.3 +/- 2.2% in the DIP and increased by 7.5 +/- 1.7% in the NDIP group (p < 0.01). Daily 6-SMT was comparable in DIP (3.28 +/- 0.87 microg/12 h) and NDIP (2.31 +/- 0.68 microg/12 h) (p = 0.39). However, while the DIP presented the physiological nocturnal increase in urinary 6-SMT (mean 8.19 +/- 1.68 microg/ 12 h), this surge of melatonin production was missing in NDIP in whom nocturnal urinary 6-SMT concentrations were not significantly different from daily levels (mean 2.56 +/- 0.79 microg/12 h). The nocturnal change in urinary 6-SMT excretion was positively correlated to the nocturnal change in MAP (R = 0.54; p = 0.031). CONCLUSIONS: NDIP hypertensive patients differ from DIP hypertensives by having an impaired nocturnal melatonin secretion. Thus, melatonin may play a role in the circadian rhythm of blood pressure in hypertensive patients.     

Radiofrequency ablation for cure of atrial flutter

Abstract Background: Atrial flutter is a common arrhythmia which frequently recurs after cardioversion and is relatively difficult to control with antiarrhythmic agents.
Aims: To evaluate the success rate, recurrence rate and safety of radiofrequency (RF) ablation for atrial flutter in a consecutive series of patients with drug refractory chronic or paroxysmal forms of the arrhythmia.
Methods: Electrophysiologic evaluation of atrial flutter included activation mapping with a 20 electrode halo cadieter placed around the tricuspid annulus and entrainment mapping from within the low right atrial isthmus. After confirmation of the arrhythmia mechanism with these techniques, an anatomic approach was used to create a linear lesion between the inferior tricuspid annulus and the eustachian ridge at the anterior margin of the inferior vena cava. In order to demonstrate successful ablation, mapping techniques were employed to show that bi-directional conduction block was present in the low right atrial isthmus.
Results: Successful ablation was achieved in 26/27 patients (96%). In one patient with a grossly enlarged right atrium, isthmus block could not be achieved. Of the 26 patients with successful ablation, mere has been one recurrence of typical flutter (4%) during a mean follow-up period of 5.5±2.7 months. This patient underwent a successful repeat ablation procedure. Of eight patients with documented clinical atrial fibrillation (in addition to atrial flutter) prior to the procedure, five continued to have atrial fibrillation following the ablation. There were no procedural complications and all patients had normal AV conduction at the completion of the ablation.
Conclusions: RF ablation is a highly effective and safe procedure for cure of atrial flutter. In patients with chronic or recurrent forms of atrial flutter RF ablation should be considered as a first line therapeutic option.     

Mutations in TAX1BP3 Cause Dilated Cardiomyopathy with Septo‐Optic Dysplasia

We describe a Bedouin family with a novel autosomal recessive syndrome characterized by dilated cardiomyopathy and septo‐optic dysplasia. Genetic analysis revealed a homozygous missense mutation in TAX1BP3, which encodes a small PDZ domain containing protein implicated in regulation of the Wnt/β‐catenin signaling pathway, as the causative mutation. The mutation affects a conserved residue located at the core of TAX1BP3 binding pocket and is predicted to impair the nature of a crucial hydrophobic patch, thereby interrupting the structure and stability of the protein, and its ability to interact with other proteins. TAX1BP3 is highly expressed in heart and brain and consistent with the clinical findings observed in our patients; a knockdown of TAX1BP3 causes elongation defects, enlarged pericard, and enlarged head structures in zebrafish embryos. Thus, we describe a new genetic disorder that expands the monogenic cardiomyopathy disease spectrum and suggests that TAX1BP3 is essential for heart and brain development.