Takayasu’s arteritis occurring under TNF blockers in a patient with spondyloarthritis: is it an association or a paradoxical effect?

Coexistence of spondyloarthritis (SpA) and Takayasu’s arteritis is not a common finding, but such cases have been discussed, particularly in the context of choice of therapy. Inhibition of inflammation by tumor necrosis factor inhibitors (TNFi) is a key aspect of the treatment of SpA and also positive effects of such treatment in concomitant large vessel vasculitis have been reported. However, TNFi is also associated with the possibility of initiating vasculitis.The present article based on a case study and the available literature is an attempt to discuss coexistence of these two diseases and the impact of treatment with biological drugs from the anti-TNF group in the course of SpA with Takayasu’s arteritis.     

Study and development of encapsulated forms of 4, 5′, 8‐Trimethylpsoralen for topical drug delivery

Trimethylpsoralen (TMP) is often used to treat skin diseases (i.e., psoriasis, vitiligo, etc.). This drug permeates moderately the skin barrier. In the present study, we investigated the effect of formulation on the improvement of TMP skin bioavailability. Three formulations were performed. Each form (liposomes, nanospheres, and EtOH solution) contained 0.05% of TMP. For each preparation, the quantity deposited on the skin surface was 250 µg (Q₀). The TMP percutaneous penetration through ex‐vivo human skin was processed by Franz^® cells (n=4) using a human albumin solution (1.4% w/v) as receiver medium. The percentages of the extracted TMP that permeated through the skin and that were retained in the skin over 24 h, were calculated with respect to Q₀. The values obtained were reported, respectively, as follows: EtOH solution (1.33 vs. 0.08%), liposomes (0.93 vs. 0.93%), and PLG‐nanospheres (0.79 vs. 3.01%). So, considering the correlation between the cumulated amounts of TMP permeated through the skin and the TMP stocked in the skin, the nanosphere form showed the higher quantity of TMP accumulated in the skin structures. On the other hand, the maximum value of the flux (ng/cm²/h) in the steady state of TMP incorporated in each formulation was at 6 h for all formulations: 173.5±1.06 (EtOH solution) > 120.4±1.06 (liposomes) > 93.82±0.88 (PLG‐nanospheres). These results indicate that the controlled release of TMP by incorporation in PLG‐nanospheres may increase drug content in the skin, while maintaining a minimal percutaneous absorption. Finally, this work shows that the PLG‐nanospheres could constitute a promising approach for controlling TMP release in order to maintain its topical activity. Drug Dev. Res. 61:86–94, 2004. © 2004 Wiley‐Liss, Inc.     

MR Spectroscopic Evidence of Brain Injury in the Non-Diagnosed Collision Sport Athlete

With growing evidence of long-term neurological damage in individuals enduring repetitive head trauma, it is critical to detect lower-level damage accumulation for the early diagnosis of injury in at-risk populations. Proton magnetic resonance spectroscopic scans of the dorsolateral prefrontal cortex and primary motor cortex were collected from high school American (gridiron) football athletes, prior to and during their competition seasons. Although no concussions were diagnosed, significant metabolic deviations from baseline and non-collision sport controls were revealed. Overall the findings indicate underlying biochemical changes, consequential to repetitive hits, which have previously gone unnoticed due to a lack of traditional neurological symptoms.     

The Effect of Sonophoresis on Topical Anesthesia: A Pilot Project

The dental anesthesia sonophoresis device (DASD) is a novel device that is intended to reduce the discomfort associated with intraoral mucosa needle puncture. The DASD produces ultrasonic energy that provides a sonophoretic effect on the oral mucosa, generating microchannels through the lipids between the keratinized cells that make up the stratum corneum. Once the topical anesthetic has permeated the stratum corneum, it quickly diffuses through the soft tissue, desensitizing the nerve endings and reducing the perception of pain caused by needle penetration. The aim of this study is to evaluate whether topical anesthesia applied using the DASD will reduce the discomfort of the needle puncture when compared to the control device. A split-mouth model, using 50 healthy subjects with puncture site at the maxillary canine vestibule, was used for this study. Subjects received a needle puncture on both sides of the mouth. Prior to the needle puncture, there was randomized application of 5% lidocaine with the DASD and a control device. Subjects rated their discomfort after needle punctures utilizing the visual analog scale pain scoring system. There was no statistically significant difference in the pain perception using the DASD versus the control device.Key Words: Dental anesthesia sonophoresis device, SonophoresisSonophoresis, which is low-frequency ultrasound, has been shown to enhance transdermal transport of various drugs, including macromolecules. Enhancement from sonophoresis occurs by disordering the structured lipids in the stratum corneum. Although sonophoresis has been shown to be effective on the skin, its effect has not been studied intraorally. The development of the dental anesthesia sonophoresis device (DASD), a device whose design was specially developed for the application of sonophoresis in the oral cavity, has opened the door for exploration in the benefits and effectiveness of sonophoresis application in the dental field. Fear of intraoral local anesthetic injection is one of the main reasons people avoid dental treatment.¹ Many investigators, using a variety of different techniques, have explored reducing the pain and discomfort of the dental injection. The majority of research has focused on the application of topical anesthesia.The results are inconsistent with regard to the effectiveness of topically applied anesthetic. Some studies show that there are no significant differences when compared to the placebo.^2–5 On the other hand, there are several studies that support the efficacy of topical anesthetic.^3,6–9Duration of application has been isolated as an important factor to achieve adequate topical anesthesia. Meechan¹⁰ summarizes that the degree of topical anesthesia penetration and its effectiveness are governed by the duration of application. It has been suggested that success of topical anesthesia is guaranteed when used in the buccal fold of either jaw after a 5-minute application.¹¹ Due to the lack of consistency in the literature regarding the effectiveness of topical anesthesia, there is need for continued research and improvement.Topical anesthetic must cross the physical barrier of the intraoral mucosa to reach the underlying nerve receptors. The free nerve endings are located close to the basal surface of the oral epithelium.¹² The location of these free nerve endings only reinforces the importance of the topical anesthetic passing through the oral mucosa barrier. The intraoral mucosa, like the skin, consists of stratified squamous epithelium with different layers of cells. The most superficial layer is the stratum corneum, which is filled with short stacks of lipid lamellae.¹³ This lipid layer makes it difficult for substances to cross the stratum corneum. To demonstrate this, Squier¹⁴ showed that horseradish peroxidase could not penetrate the top 3 layers of the oral mucosa of 3 mammals when applied topically.Attempts have been made to improve the penetration of topical anesthetics across this anatomic barrier. Hutchins et al⁷ studied the effect of vibration with a placebo and vibration with 20% benzocaine on pain of intraoral injections, and found vibration had no effect on reducing pain. Others have studied the use of iontophoresis and phonophoresis for application of anesthesia.^15,16 Research suggests that skin anesthesia by application of a topical anesthetic can be expedited through iontophoresis; however, this still requires a minimum of 10 minutes at relatively high voltage.¹⁷Ultrasound has been shown to enhance transdermal transport of various drugs, including macromolecules. This type of enhancement is termed sonophoresis, indicating the enhanced transport of molecules under the influence of ultrasound.¹⁸The DASD is a novel device intended to expedite penetration of topical anesthetic with a faster onset of clinical effectiveness. The DASD is a portable, battery-powered device that simultaneously generates ultrasonic energy and sonic vibration in a small applicator head that can easily reach and adapt to injection sites in the oral cavity. The ultrasonic energy is in small bursts of 300–350 kHz that provide a sonophoretic effect on the oral mucosa. The manufacturer claims the DASD works by generating microchannels through the lipids in the stratum corneum. The sonic vibration is provided simultaneously with the ultrasonic energy in the form of sinusoidal motion ranging from 200–300 Hz. This vibration helps to randomize and distribute the sensation associated with the ultrasonic energy. Once the topical anesthetic has permeated the stratum corneum, it quickly diffuses through the soft tissue, desensitizing the nerve endings. The purpose of this study is to evaluate whether topical anesthesia applied using the DASD will reduce the discomfort of the needle puncture when compared to the control device. The null hypothesis is that there is no difference of perceived discomfort between the DASD and the control device (CD).     

Atrial fibrillation during myocardial infarction with and without ST segment elevation

INTRODUCTION: The occurrence of atrial fibrillation (AF) in the acute phase of myocardial infarction with ST segment elevation is common and responsible for an excess hospital mortality. The aim of this work was to define the incidence, predictive factors, and the prognostic impact of AF during MI with and without raised ST segment in the RICO study. PATIENTS AND METHODS: Between January 2001 and July 2003, 1701 patients were included in this study: 130 (7.6%) had AF in the first 24 hours of management (AF+ group); 1571 (92.4%) remained in sinus rhythm (AF- group). RESULTS: Among the 1701 patients included in this study, 1197 (70.4%) had MI with raised ST and 504 (29.6%) had MI without raised ST. The incidence of AF was identical whatever the type of MI (7.6% with raised ST versus 7.7% without, p=0.334). The presence of Killip class >2 on admission and chronic obstructive pulmonary disease were independent predictive factors for the occurrence of AF (OR=3.84, p=0.007, and OR=2.47, p=0.014 respectively). The presence of AF was significantly associated with the occurrence of ventricular arrhythmia and/or cardiovascular mortality during admission in the non-selected MI population whatever the type of MI (raised ST ; AF+; 34% and AF-; 18%, p<0.01 versus without raised ST; AF+; 36% and AF-; 16%, p = 0.01). CONCLUSION: This study provides evidence that the incidence of AF during the first 24 hours of MI, as well as its poor prognosis, are identical whether or not there is ST segment elevation.