Evaluation of Glucose Uptake and Uncoupling Protein 1 Activity in Adipose Tissue of Diabetic Mice upon β-Adrenergic Stimulation

Molecular Imaging and Biology - Regulation of metabolic activity in adipose tissue is of great concern for treating obesity. This study aimed to evaluate the adrenergic regulation of glucose uptake...     

Noninvasive Transcranial Stimulation of Rat Abducens Nerve by Focused Ultrasound

Nonpharmacologic and nonsurgical transcranial modulation of the nerve function may provide new opportunities in evaluation and treatment of cranial nerve diseases. This study investigates the possibility of using low-intensity transcranial focused ultrasound (FUS) to selectively stimulate the rat abducens nerve located above the base of the skull. FUS (frequencies of 350 kHz and 650 kHz) operating in a pulsed mode was applied to the abducens nerve of Sprague-Dawley rats under stereotactic guidance. The abductive eyeball movement ipsilateral to the side of sonication was observed at 350 kHz, using the 0.36-msec tone burst duration (TBD), 1.5-kHz pulse repetition frequency (PRF), and the overall sonication duration of 200 msec. Histologic and behavioral monitoring showed no signs of disruption in the blood brain barrier (BBB), as well as no damage to the nerves and adjacent brain tissue resulting from the sonication. As a novel functional neuro-modulatory modality, the pulsed application of FUS has potential for diagnostic and therapeutic applications in diseases of the peripheral nervous system.     

Can Surface Neuromuscular Electrical Stimulation of the Wrist and Hand Combined With Routine Therapy Facilitate Recovery of Arm Function in Patients With Stroke?

Rosewilliam S, Malhotra S, Roffe C, Jones P, Pandyan AD. Can surface neuromuscular electrical stimulation of the wrist and hand combined with routine therapy facilitate recovery of arm function in patients with stroke?ObjectiveTo investigate whether treatment with surface neuromuscular electrical stimulation to the wrist extensors improves recovery of arm function in severely disabled patients with stroke.DesignSingle blinded randomized controlled trial.SettingAcute stroke unit and stroke rehabilitation wards of a university hospital.ParticipantsPatients with no upper limb function (Action Research Arm Test [ARAT] score 0) (N=90; mean age ± SD, 74±11y; 49% men) were recruited to the study within 6 weeks of stroke. Only 67 participants were alive at the end of the study and data from 66 of these people were analyzed.InterventionsParticipants were randomized to surface neuromuscular electrical stimulation using surface electrical stimulators for 30 minutes, twice in a working day for 6 weeks in addition to standardized upper limb therapy or just standardized upper limb therapy.Main Outcome MeasureThe primary outcome measure was the ARAT score. Assessments were made at baseline and at 6, 12, 24, and 36 weeks after recruitment.ResultsThere were statistically significant improvements in measures of wrist extensor (mean difference 0.5; 95% confidence interval [CI], 0.0–1.0) and grip strength (mean difference 0.9; 95% CI, 0.1–1.7) over the treatment period. Arm function (ARAT score) was not significantly different between the groups over the treatment period at 6 weeks (mean difference 1.9; 95% CI, ?2.9 to 6.8) or over the study period at 36 weeks (mean difference 6.4; 95% CI, ?1.8 to 14.7), and the rate of recovery was not significantly different (mean difference 0.7; 95% CI, ?0.2 to 1.6).ConclusionsIn patients with severe stroke, with no functional arm movement, electrical stimulation of wrist extensors improves muscle strength for wrist extension and grip, and larger studies are required to study its influence on arm function.     

Stimulation of pulmonary big endothelin-1 and endothelin-1 by antithrombin III: a rationale for combined application of antithrombin III and endothelin antagonists in sepsis-related acute respiratory distress syndrome?

OBJECTIVES: Antithrombin (AT) III reduces lung damage in animal models of septic acute respiratory distress syndrome (ARDS), which is generally attributed to stimulation of endothelial prostacyclin synthesis. However, clinical studies have failed so far to demonstrate mortality reduction by application of AT III. We investigated whether AT III stimulates pulmonary prostacyclin release. In addition, we hypothesized that it may promote pulmonary endothelins, thereby mitigating its own protective effect in the course of ARDS. DESIGN: Controlled experiment using isolated organs. SETTING: Experimental laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Isolated lungs were perfused over 120 mins in recirculatory mode in the presence of 50 microg/mL endotoxin (n = 11), 2U/mL AT III (n = 10), 5 U/mL AT III (n = 13), endotoxin plus 2 U/mL AT III (n = 5), or vehicle alone (controls, n = 13), respectively. MEASUREMENTS AND MAIN RESULTS: We determined the effects of AT III on vascular release of thromboxane B2, 6-keto-prostaglandin-F1alpha, big endothelin-1, and endothelin-1. Control lungs released 59+/-23 pg/mL thromboxane B2, 1,480+/-364 pg/mL 6-keto-prostaglandin-F1alpha, 15.2+/-4.5 pg/mL big endothelin-1, and 0.46+/-0.13 pg/mL endothelin-1. Exposure to endotoxin increased thromboxane B2 release 2.9-fold, 6-keto-prostaglandin-F1alpha release 1.6-fold, and endothelin-1 1.6-fold (p < .05 each); levels of big endothelin-1 were unchanged. AT III at 2 U/mL elevated production of big endothelin-1 (1.7-fold) and endothelin-1 (1.2-fold) (p < .05 for both). AT III at 5 U/mL enhanced levels of big endothelin-1 (1.6-fold) and endothelin-1 (1.3-fold) (p < .05 for both). Neither dose of AT III affected thromboxane B2 or 6-keto-prostaglandin-F1alpha concentrations. Application of 2 U/mL AT III plus endotoxin stimulated big endothelin-1 production (2.6-fold) compared with endotoxin or AT III alone (p < .05 for both), but did not further elevate endothelin-1 release. CONCLUSIONS: AT III does not stimulate pulmonary prostacyclin, but promotes pulmonary release of big endothelin-1 and endothelin-1 under basal and, particularly, under septic conditions, which may blunt the AT III-induced lung protection during ARDS. Therefore, we suggest combined application of AT III and endothelin antagonists in animal models of septic ARDS.     

Is Transcranial Direct Current Stimulation (tDCS) Effective for the Treatment of Pain in Fibromyalgia? A Systematic Review and Meta-Analysis

Background: Fibromyalgia is a debilitating condition characterized by chronic widespread pain. It is believed to be caused by dysfunction of the central nervous system (CNS) but current treatments are largely ineffective. Transcranial direct current stimulation (tDCS), a neuromodulation technique that targets the CNS, may offer a new line of treatment. Objective: To systematically review the most up-to-date literature and perform a meta-analysis of the effects of tDCS on pain intensity in fibromyalgia. Methods: The following databases were searched from inception: Medline (Ovid), PsychInfo, CINAHL, Cochrane Library, and Web of Science. Studies were eligible if they were randomized controlled trials, quasi-randomized trials, and nonrandomized. Crossover and parallel-group design studies were included. Risk of bias was assessed for all included studies. Meta-analysis was conducted on studies investigating pain intensity after tDCS in participants with fibromyalgia and analyzed using standardized mean difference and 95% confidence intervals. Results: Fourteen clinical studies were included. Ten were controlled trials and 4 were within-subjects crossover studies. Meta-analysis of data from 8 controlled trials provides tentative evidence of pain reduction when active tDCS is delivered compared to sham. However, substantial statistical heterogeneity and high risk of bias of primary studies prevent more conclusive recommendations being made. Conclusions: tDCS is a safe intervention with the potential to lower pain intensity in fibromyalgia. However, there is a need for more empirical research of the neural target sites and optimum stimulation parameters to achieve the greatest effects before conducting further clinical studies.PerspectiveThis systematic review and meta-analysis synthesizes current evidence for the clinical effectiveness of tDCS in the treatment of fibromyalgia pain. There is only tentative evidence of pain reduction when active tDCS is compared to sham. High heterogeneity and risk of bias across studies suggest a need for further empirical research.     

Evidence for Transcutaneous Electrical Nerve Stimulation in the Management of Low Back Pain?

Abstract

Low back pain is a huge burden on society and the health care system, and cost the UK over £1.5 billion in 1998 alone. One of the modalities available to treat this condition is transcutaneous electrical nerve stimulation (TENS), a form of electrotherapy that is inexpensive and widely used by clinicians and patients alike for many conditions including pain relief. The aim of this review was to determine whether TENS is an effective treatment for pain relief in people with low back pain. This paper outlines the evidence for the use of TENS for low back pain, and recommends that future research should try to map specific TENS parameters with each of the different types of low back pain.     

Clinical Use of Neuromuscular Electrical Stimulation for Neuromuscular Rehabilitation: What Are We Overlooking?

The clinical success of neuromuscular electrical stimulation (NMES) for neuromuscular rehabilitation is greatly compromised by the poor consideration of different physiological and methodological issues that are not always obvious to the clinicians. Therefore, the aim of this narrative review is to reexamine some of these fundamental aspects of NMES using a tripartite model perspective. First, we contend that NMES does not actually bypass the central nervous system but results in a multitude of neurally mediated responses that contribute substantially to force generation and may engender neural adaptations. Second, we argue that too much emphasis is generally placed on externally controllable stimulation parameters while the major determinant of NMES effectiveness is the intrinsically determined muscle tension generated by the current (ie, evoked force). Third, we believe that a more systematic approach to NMES therapy is required in the clinic and this implies a better identification of the patient-specific impairment and of the potential “responders” to NMES therapy. On the basis of these considerations, we suggest that the crucial steps to ensure the clinical effectiveness of NMES treatment should consist of (1) identifying the neuromuscular impairment with clinical assessment and (2) implementing algorithm-based NMES therapy while (3) properly dosing the treatment with tension-controlled NMES and eventually amplifying its neural effects.     

Spinal Cord Stimulation in the Treatment of Cancer-Related Pain: “Back to the Origins”

Spinal cord stimulation (SCS) has been used in the treatment of chronic pain for more than 40 years. The most common indication for SCS in the USA is failed back surgery syndrome (FBSS). Interestingly, the first two spinal cord stimulators ever implanted were in patients suffering from bronchogenic carcinoma and pelvic cancer, respectively. While cancer accounts for millions of deaths each year in the USA, pain is often the first sign of malignancy. An increasing number of people suffer from cancer-related pain each year and many receive suboptimal relief. Given the demonstrated value of spinal cord stimulation in the treatment of neuropathic pain, spinal cord stimulation should be considered "earlier" as an adjunct to the treatment of cancer-related pain. In addition, with the improving survival rates associated with advances in cancer treatment, spinal cord stimulation may help reduce the risk of development of chronic neuropathic pain in survivors.     

In Vivo Microbial Stimulation Induces Rapid CD40 Ligand–independent Production of Interleukin 12 by Dendritic Cells and their Redistribution to T Cell Areas

The early induction of interleukin (IL)-12 is a critical event in determining the development of both innate resistance and adaptive immunity to many intracellular pathogens. Previous in vitro studies have suggested that the macrophage (MΦ) is a major source of the initial IL-12 produced upon microbial stimulation and that this response promotes the differentiation of protective T helper cell 1 (Th1) CD4⁺ lymphocytes from precursors that are primed on antigen-bearing dendritic cells (DC). Here, we demonstrate by immunolocalization experiments and flow cytometric analysis that, contrary to expectation, DC and not MΦ are the initial cells to synthesize IL-12 in the spleens of mice exposed in vivo to an extract of Toxoplasma gondii or to lipopolysaccharide, two well characterized microbial stimulants of the cytokine. Importantly, this production of IL-12 occurs very rapidly and is independent of interferon γ priming or of signals from T cells, such as CD40 ligand. IL-12 production by splenic DC is accompanied by an increase in number of DCs, as well as a redistribution to the T cell areas and the acquisition of markers characteristic of interdigitating dendritic cells. The capacity of splenic DC but not MΦ to synthesize de novo high levels of IL-12 within hours of exposure to microbial products in vivo, as well as the ability of the same stimuli to induce migration of DC to the T cell areas, argues that DC function simultaneously as both antigen-presenting cells and IL-12 producing accessory cells in the initiation of cell-mediated immunity to intracellular pathogens. This model avoids the need to invoke a three-cell interaction for Th1 differentiation and points to the DC as both a sentinel for innate recognition and the dictator of class selection in the subsequent adaptive response.Interleukin 12 (IL-12) is a key cytokine in the induction of cell-mediated immunity to intracellular pathogens. In the innate response to these microbial agents, IL-12 triggers the production of IFN-γ and TNF from unsensitized NK and T cells. At the same time, IL-12 selectively promotes the differentiation of Th1 CD4⁺ cells, which produce the same effector lymphokines upon restimulation with antigen. Thus, the induction of IL-12 early in infection initiates innate resistance to the pathogen while ensuring the induction of the correct class of adaptive host response (1).Macrophages (MΦ)¹ activated by microbial stimulation produce high levels of IL-12, and it has been assumed that these cells provide the major source of the cytokine in Th1 response initiation (2). Indeed, in vitro studies with TCR transgenic CD4⁺ cells primed by antigen-pulsed cells showed IL-12–producing MΦ to be highly effective in inducing selective Th1 cell differentiation (3). However, the model of class selection suggested by these experiments requires that both antigen-bearing dendritic cells (DC) and IL-12–producing MΦ travel from the site of infection to lymphoid tissues where the responding T cells are found, and at present, no evidence exists for such MΦ migration. Furthermore, a model in which IL-12 produced by MΦ acts in a paracrine fashion to drive Th1 development of microbe-specific T cells would lead to Th1 differentiation of all recently activated precursors in the local microenvironment, thus limiting the ability of the immune system to independently control Th1 responses to different antigens and potentially leading to inflammatory responses to self-antigens. A similar objection applies to models of type 1 response initiation involving other “third-party” IL-12–producing cells such as neutrophils (4).In contrast to MΦ, DC constitute a highly efficient system for capturing antigens in the periphery and delivering them to the T cell areas of lymphoid tissues (5, 6). It is believed that this allows perusal of peripheral antigens by T cells that recirculate between the blood and lymphoid compartments. In addition, DC possess many specializations that allow them to function as efficient APCs, such as high levels of MHC products, adhesion and costimulatory molecules, extensive surface area, and high motility (5, 6). These properties suggest that DC act as the priming APC for most T cell responses and thus would be ideally placed to produce IL-12 at a site where it acts directly on those T cells responding to DC-presented immunogenic MHC–peptide complexes derived from infectious agents.The early synthesis of IL-12 is of crucial importance in determining both innate and adaptive host resistance to the intracellular protozoan, Toxoplasma gondii, and live replicative forms (tachyzoites) as well as parasite extracts have been shown to be potent inducers of the cytokine from peritoneal inflammatory MΦ in vitro (7–10). Nevertheless, inflammatory MΦ populations that are elicited by local injection of an irritant, or, for that matter, any population obtained after in vivo or in vitro manipulation, may not be representative of the naive cells that initiate IL-12 responses. Therefore, we have used immunolocalization techniques to identify the cells first making IL-12 after in vivo stimulation with T. gondii products or LPS. Our results clearly demonstrate that DC, not MΦ, are the cells involved in the IL-12 response to these microbial stimuli, which also simultaneously trigger DC recruitment to the T cell areas of the spleen. Together, these findings support a two cell model of in vivo T cell activation in which the DC serves as both the APC and the IL-12–producing initiator of the Th1 response.     

Examination of Factors Related to the Effect of Improving Gait Speed With Functional Electrical Stimulation Intervention for Stroke Patients

Background

Functional electrical stimulation (FES) for patients with stroke and foot drop is an alternative to ankle foot orthoses. Characteristics of FES responders and nonresponders have not been clarified.

Relation research of the expression and function of VEGF and its receptor

VEGF stimulates the formation of vessle and proliferation of endothelial cells．VEGF and its rece ptor，FLK －１have the function of chemotaxing and division．Now ，it is well known that VEGF is involved in growth and metastasis of a number of experimental tu－mors［１］．Neuroblastoma is characterized by higher malignace，early metastasis，abundant vessels．The mechanism of its high malignace is not clear now．We detected expressio n and distribution of VEGF and its receptor in neruob…     

Management of Phrenic Stimulation in CRT Patients over the Long Term: Still an Unmet Need ?

Background: Phrenic stimulation (PS) may cause intolerable symptoms and prevent CRT delivery in 2–5% of patients. We sought to ensure effective cardiac resynchronization therapy (CRT) delivery by management of PS at the left ventricular (LV) target site. Methods and Results : Two hundred and eleven consecutive patients received a CRT device despite PS occurrence at the LV target site at implantation, when a PS‐LV difference >2V was achieved by LV stimulation programming (cathode, pacing vector). PS management strategy both at implantation and at follow‐up (FU) aimed to keep the target LV implantation site. LV reverse remodeling was assessed by echocardiography before implantation and at follow‐up. LV lead placement was lateral/posterolateral in all the 211 patients; 51 of 211 had detectable PS at FU, 26 of 211 (12.3%) were symptomatic. Symptoms occurred more frequently when PS‐LV difference was <3V (16/16 vs 10/35, P < 0.001). Cathode and pacing vector reprogramming improved the PS‐LV difference and symptoms in 14 of 23 patients. LV output as threshold +0.5V was helpful to manage PS symptoms in patients with a PS‐LV ≤2V at FU. Median FU was 34.9 (16–50) months: 12 patients had tolerable PS symptoms, 76% (39/51) were objective responders at echocardiography compared to 74% (119/160) in patients without PS (P = NS). Conclusions : CRT delivery at long term is feasible despite PS at the target LV site. PS management is mandatory in about 12.3% of patients at FU, with 6.6% remaining symptomatic. Symptoms improve at FU when a PS‐LV >3V is achieved. Further improvement in lead manufacturing and pacing electronics are awaited to meet this clinical need. (PACE 2011; 34:1201–1208)     

Manifestations and causes of psychological and behavioral problems in infant patients and patients of early age

Largeamountsclinicalfactsdemonstratethatmanydiseasescaninduceemotionaldisturbancesandpsychologicalproblemssuchasfear,anxiety,restlessness,agitationandirritabilityininfantilepatientsandpatientsofearlyage.Theauthorwouldliketodiscussbrieflyseveralcommonpsychologicalandbehavioralproblemsandthecorrespondingcausesofthem.1CommonpsychologicalandbehavioralproblemsininfantpatientsandpatientsofearlyageCryingandmakingnoise:Cryingandmakingnoiseisasignalinfantsandchildrenusetoconveylargeamountsofinformation…     

Manifestations and Causes of psychological and behavioral problems in infant patients and patients of early age

Lage amounts clinical facts demonstrate that many diseases can induce emotional disturbances and psychological problems such as fear,anxiety,restlessness,agitation and irritability in infantile patients and patients of early age.The author would like to discuss briefly several common psychological and behavioral problesms and the corresponding causes of them.     

Efficacy and tolerability of a combination of Lyprinol® and high concentrations of EPA and DHA in inflammatory rheumatoid disorders

This 12-week drug-monitoring study was conducted to evaluate the efficacy of Sanhelios Mussel Lyprinol Lipid Complex on 50 adult men and women with inflammatory rheumatoid arthritis. A total of 34 patients required drug therapy before and during the study. By the end of the study, 21 (62%) patients were able to reduce their dosage and 13 were able to terminate drug therapy. At the end of the treatment period, 38% were regarded symptom free, and the number of patients with severe pain decreased significantly from 60% at baseline to 25% at the completion of the trial. A significant effect was observed for each investigated parameter. The special combination of Lyprinol and omega-3 fatty acids was generally very well tolerated, with only one, nonserious adverse event (mild nausea) reported. This dietary supplement may therefore be considered an effective and well-tolerated component of treatment regimens for inflammatory rheumatoid arthritis.     

Experience of prevention and treatment of deep burn of hand

INTRODUCTIONHowtopreventhanddeformitycausedbyburn,restoreappearanceandworkingabilityhasbeenalwaysthemainproblem,thefollow-ingisthereportaboutcausesofdeformityandexperienceofpre-ventionandtreatment.GENERALDATA2037casesofburntreatedfromJanuary1997toOctober2002amongincluding957casesofburnofhandsandtheincidencewas46.9%amongwhichwere229casesofdeepburnand195pa-tientsreceivedearlysurgicaltreatment.6patients(15fingers)un-derwentfingeramputation.38casesneededplasticsbecauseofscardeformityinlat…     

Is Automatic Mode Switching Effective for Atrial Arrhythmias Occurring at Different Rates? A Study of the Efficacy of Automatic Mode and Rate Switching to Simulated Atrial Arrhythmias by Chest Wall Stimulation

Automatic mode switching (AMS) is a useful means to avoid rapid ventricular response during atrial fibrillation (AF), but AMS cannot occur if the detected atrial rate during AF is below the mode switching criteria. This may be the result of antiarrhythmic medications, or when the atrial events fall within the atrial blanking period, or if the atrial amplitudes during AF are too small to be sensed. We hypothesize that the addition of an automatic rate switching (ARS) algorithm may complement AMS response during AF with different detected atrial rates. We studied the Marathon DDDR pacemaker (Model 294-09, Intermedics Inc.) with the AMS and ARS algorithms that are independently programmable but can also operate in combination. AF sensed above the AMS rate (160 beats/min) will lead to VDIR pacing, whereas AF below AMS rate will be tracked at an interim rate as dictate by the ARS, at a ventricular response that is 20 beats/min above the sensor indicated rate. Atrial tachyarrhythmias were simulated by chest wall stimulation (CWS). CWS was applied to 33 patients (16 men, 17 women, mean age 69 +/- 11 years) with a Marathon DDDR pacemaker using an external pacer to simulate AF occurring at two rate levels: above the AMS rate (programmed at 160 beats/min) at 180 beats/min and below the AMS rate at 120 beats/min. The maximum, minimum, and mean ventricular rates during CWS in DDDR mode with AMS alone, ARS alone, and their combination were compared. During CWS at 120 beats/min, the AMS plus ARS setting showed a mean ventricular rate of 79 +/- 3 beats/min and 124 +/- 14 beats/min in the AMS setting alone (P < 0.01). With CWS at 180 beats/min, the mean ventricular rate in the AMS plus ARS setting compared to the AMS setting alone was not significantly different. However, the variation in ventricular pacing rate was 7 +/- 14 beats/min in the AMS plus ARS setting and 40 +/- 42 beats/min in the AMS setting (P < 0.05). In conclusion, AMS is effective for simulated atrial tachyarrhythmias sensed above the AMS rate. Combined AMS with ARS is useful to handle simulated atrial tachyarrhythmia at a slower rate and to avoid rate fluctuation during AMS. There is also a possibility that this can be applied to the naturally occurring atrial tachyarrhythmias.     

Three-Year Cost-effectiveness Model for Non–Animal Stabilized Hyaluronic Acid and Dextranomer Copolymer Compared With Sacral Nerve Stimulation After Conservative Therapy for the Management of Fecal Incontinence

Background

Two new therapies for fecal incontinence (FI) are now available: non–animal stabilized hyaluronic acid and dextranomer copolymer (NASHA/Dx) and sacral nerve stimulation (SNS).

Purpose

This study aimed to determine the cost-effectiveness of NASHA/Dx compared with SNS and conservative therapy (CT) for the treatment of FI after CT failure.

Methods

Decision tree models with Markov subbranches were developed to compare all direct costs and outcomes during a 3-year period from the viewpoint of the US third-party payer. Costs (in 2013 US dollars) of devices, medical and surgical care, and hospitalization were included. Outcomes included quality-adjusted life-years (QALYs) and incontinence-free days (IFDs). Both costs and outcomes were discounted at an annual rate of 3%. The incremental cost-effectiveness ratio was calculated for each outcome. One-way and probabilistic sensitivity analyses were performed to examine robustness of results and model stability. A budget impact analysis was also undertaken to estimate the potential cost and savings of NASHA/Dx for a payer with 1,000,000 covered lives.

Results

For the 3-year cost-effectiveness models, the expected cost was $9053 for CT, $14,962 for NASHA/Dx, and $33,201 for SNS. The numbers of QALYs were 1.769, 1.929, and 2.004, respectively. The numbers of IFDs were 128.8, 267.6, and 514.8, respectively. The incremental cost-effectiveness ratios per additional IFD gained were $42.60 for NASHA/Dx vs CT, $73.76 for SNS vs NASHA/Dx, and $62.55 for SNS vs CT. The incremental costs per QALY gained were $37,036 for NASHA/Dx vs CT, $244,509 for SNS vs NASHA/Dx, and $103,066 for SNS vs CT. The budget impact analysis evaluated the financial effect on the health care system of the use of NASHA/Dx and SNS. For the scenarios evaluated, when all of the patients receive NASHA/Dx, the net annual effect to the health care payer budget ranged from $571,455 to $2,857,275. When all of the patients receive SNS, the net annual effect to the health care payer budget ranged from $1,959,323 to $9,796,613.

Conclusion

Both NASHA/Dx and SNS have produced significant improvements in FI symptoms for affected patients. NASHA/Dx is a cost-effective and more efficient use of resources for the treatment of FI when compared with SNS. The budget impact analysis suggests that although reimbursement for NASHA/Dx treatment initially adds costs to the health care system, it is significantly less expensive than SNS for patients who are candidates for either treatment.     

Effect of Low-Intensity Pulsed Ultrasound Stimulation,Extracorporeal Shockwaves and Radial Pressure Waves on Akt,BMP-2, ERK-2, FAK and TGF-β1 During Bone Healing in Rat Tibial Defects

An experimental study was conducted to determine whether low-intensity pulsed ultrasound stimulation (LIPUS), extracorporeal shockwave treatment (ESWT) and radial pressure wave treatment (RPWT) modulate Akt, bone morphogenetic protein-2 (BMP-2), extracellular signal-regulated kinase-2 (ERK-2), focal adhesion kinase (FAK) and transforming growth factor-β1 (TGF-β1) during bone healing in rat tibial defects. Rat tibial defects were exposed to 500 shots of ESWT delivered at 0.12 mJ/mm², 500 impulses of RPWT operated at 2.0 bar or to daily 20-min 30 mW/cm² LIPUS. Following 1, 3 and 6 wk, bones were harvested to determine the expression and activity of Akt, BMP-2, ERK-2, FAK and TGF-β1. Animals exposed to ultrasound were followed up to 3 wk. Protein expression and activity were unchanged following LIPUS treatment. ESWT increased Akt activity 2.11-fold (p = 0.043) and TGF-β1 expression 9.11-fold (p = 0.016) at 1 wk and increased FAK activity 2.16-fold (p = 0.047) at 3 wk. RPWT increased FAK activity 2.6-fold (p = 0.028) at 3 wk and decreased Akt expression 0.52-fold (p = 0.05) at 6 wk. In conclusion, the protocols employed for ESWT and RPWT modulated distinct signaling pathways during fracture healing, while LIPUS standard protocol did not change the usual signaling pathways of the proteins investigated. Future studies are required to monitor osteogenesis so that the biologic meaning of our results can be clarified.