Does the Application of Tecar Therapy Affect Temperature and Perfusion of Skin and Muscle Microcirculation? A Pilot Feasibility Study on Healthy Subjects.

Background: Tecar therapy (TT) is an endogenous thermotherapy used to generate warming up of superficial and deep tissues. TT capability to affect the blood flow is commonly considered to be the primary mechanism to promote tissue healing processes. Despite some preliminary evidence about its clinical efficacy, knowledge on the physiologic responses induced by TT is lacking. Objective: The aim of this quantitative randomized pilot study was to determinate if TT, delivered in two modes (resistive and capacitive), affects the perfusion of the skin microcirculation (PSMC) and intramuscular blood flow (IMBF). Design: A randomized controlled pilot feasibility study. Subjects: Ten healthy volunteers (n = 4 females, n = 6 males; mean age 35.9 ± 10.7 years) from a university population were recruited and completed the study. Intervention: All subjects received three different TT applications (resistive, capacitive, and placebo) for a period of 8 min. Outcome measures: PSMC, IMBF, and the skin temperature (ST) were measured pre- and post-TT application using power Doppler sonography, laser speckle contrast imaging (LSCI), and infrared thermography. Results: Compared with placebo application, statistically significant differences in PSMC resulted after both the resistive (p = 0.0001) and the capacitive (p = 0.0001) TT applications, while only the resistive modality compared with the placebo was capable to induce a significant change of IMBF (p = 0.013) and ST (p = 0.0001). Conclusions: The use of power Doppler sonography and LSCI enabled us to evaluate differences in PSMC and IMBF induced by TT application.

Dosimetric issues with simplified homogeneous body models in low frequency magnetic field exposure assessment.

A simplified procedure, using circular disk models with homogeneous electric conductivity as representations for different body parts, has been proposed recently by product standard IEC 62822-3 for the assessment of magnetic field exposure in proximity to current-carrying conductors of welding equipment. Based on such simplified models, worst case coupling coefficients CCEi(I), i.e. maximum induced electric field strength, normalised for current and frequency, for body parts at different distances d to straight single and double wire arrangements, as well as rectangular loop-shaped current paths are tabulated in the standard. In this work we compared CCEi(I) values obtained by numerical computations with detailed anatomical models of the hand/forearm with the corresponding values given in IEC 62822-3 for current-carrying single wire conductors along the forearm at distances d = 30, 50 and 100 mm, respectively. Our results clearly indicated that the CCEi(I) given in the standard may substantially underestimate the actual exposure. Using average values for tissue conductivities the observed extent of underestimation was up to 8.9 dB (factor 2.79) and may be even higher for worst case combinations of tissue conductivities. The reasons for this substantial underestimation are the oversimplified geometry, i.e. the circular disk does not reflect anatomical constrictions of the induction area present in realistic hand/forearm geometries, as well as the missing conductivity contrast between different tissues in the homogeneous disk models. Results of exposure assessment and corresponding minimum distances to components of welding equipment obtained by the simplified disk model approach suggested by IEC 62822-3 should therefore be considered with caution.

Right lateral versus left lateral view for forearm coronary angiography. An operator radiation exposure and image quality study.

OBJECTIVES: The aim of this study was to analyze the operator radiation exposure (ORE) and the image quality in a coronary angiography (CA) of the standard left lateral view (LLV) and compare it with an alternative right lateral view (RLV). BACKGROUND: Interventional cardiologists are exposed to high doses of scatter radiation, especially in angulated projections. METHODS: We prospectively included consecutive patients who underwent diagnostic CA. A standard +90° LLV and an alternative RLV (-90°) were done in each patient with the same protocol. The operator effective dose rate (mSv/h) was determined for each projection with digital dosimeters located in the collar, waist and knee. The image quality of both the LLV and RLV was analyzed and compared to a standard projection. RESULTS: 116 patients were enrolled; left coronary artery (LCA) was assessed in 52 patients and right coronary artery (RCA) in 64 patients. The ORE was significantly lower with the RLV compared to the conventional LLV with a maximum ORE reduction of 91.5% in the operator waist (LLV: 6.84 mSv h-1 versus RLV: 0.58 mSv h-1, p < 0.001). No significant differences in image quality were observed for the RCA in both projections. For the LCA, a slight loss of quality was observed with the RLV. CONCLUSIONS: -90° RLV is associated with a significant decrease in ORE compared to the conventional +90° LLV without losing image resolution for the RCA and resulting in a slight quality loss for the LCA evaluation. The RLV should be the first choice for RCA evaluation. For the LCA, the RLV loss of resolution should be balanced with the benefit of minimizing ORE, mainly in cases with long fluoroscopy times, such as complex percutaneous coronary interventional procedures.

Reliable assessment of forearm photoageing by high-frequency ultrasound: a cross-sectional study.

OBJECTIVE: High-frequency ultrasound is a non-invasive tool used in skin ageing research to assess dermis thickness and echogenicity. This study evaluated the reliability of a range of high-frequency ultrasound parameters and tested their correlation with age and a validated clinical scale for the assessment of forearm skin photoageing; the difference between two body sites according to environmental exposition patterns was also investigated. METHODS: Twenty-three volunteers aged 28-82 years were divided into three groups according to forearm photoageing degree. A 20 MHz ultrasound unit was used to obtain cross-sectional images of the skin by two trained investigators on two different sites: the dorsal forearm (chronically photoexposed skin) and the proximal medial arm (non-photoexposed skin). Several echogenicity parameters were studied for each skin compartment: total dermis, upper dermis and lower dermis, and the ratio between upper and lower dermis. RESULTS: The intraclass correlation coefficient (for complete agreement) between investigators was higher for upper and total dermis echogenicity measures compared with the lower dermis. At the non-photoexposed site, the upper and lower dermis parameter ratio was better correlated with age. At the photoexposed area, total dermis parameters demonstrated higher correlations with clinical score. CONCLUSION: The authors discuss the choice of parameters for forearm photoageing assessment using high-frequency ultrasound.

Phase IIB Randomized Study of Topical Difluoromethylornithine and Topical Diclofenac on Sun-Damaged Skin of the Forearm.

Prevention of nonmelanoma skin cancers remains a health priority due to high costs associated with this disease. Diclofenac and difluoromethylornithine (DFMO) have demonstrated chemopreventive efficacy for cutaneous squamous cell carcinomas. We designed a randomized study of the combination of DFMO and diclofenac in the treatment of sun-damaged skin. Individuals with visible cutaneous sun damage were eligible. Subjects were randomized to one of the three groups: topical DFMO applied twice daily, topical diclofenac applied daily, or DFMO plus diclofenac. The treatment was limited to an area on the left forearm, and the duration of use was 90 days. We hypothesized that combination therapy would have increased efficacy compared with single-agent therapy. The primary outcome was change in karyometric average nuclear abnormality (ANA) in the treated skin. Individuals assessing the biomarkers were blinded regarding the treatment for each subject. A total of 156 subjects were randomized; 144 had baseline and end-of-study biopsies, and 136 subjects completed the study. The ANA unexpectedly increased for all groups, with higher values correlating with clinical cutaneous inflammation. Nearly all of the adverse events were local cutaneous effects. One subject had cutaneous toxicity that required treatment discontinuation. Significantly more adverse events were seen in the groups taking diclofenac. Overall, the study indicated that the addition of topical DFMO to topical diclofenac did not enhance its activity. Both agents caused inflammation on a cellular and clinical level, which may have confounded the measurement of chemopreventive effects. More significant effects may be observed in subjects with greater baseline cutaneous damage.

Correlation between treatment time, photobleaching, inflammation and pain after photodynamic therapy with methyl aminolevulinate on tape-stripped skin in healthy volunteers.

Photodynamic therapy (PDT) is an attractive treatment option for skin diseases such as actinic keratosis, since large skin areas can be treated with high response rates and good cosmetic outcomes. Nevertheless inflammation and pain are still major side effects. The aim of this study was to investigate the extent to which less time-consuming PDT treatment regimens using methyl aminolevulinate (MAL) decrease protoporphyrin IX (PpIX) photobleaching, inflammation and pain. Twenty-four healthy volunteers were treated with 4 different interventions on each forearm. All 8 fields were tape-stripped 10 times. On the right arm MAL was applied for 20, 40, 60 or 180 min, followed by further incubation after wiping off MAL until 180 min after start and then illuminating with red light 180 min after start. On the left arm MAL or vehicle was applied for 30, 60, or 90 min and illuminated immediately after MAL removal. PpIX fluorescence, photobleaching, objective and subjective erythema (as a measure for inflammation), pigmentation and pain were measured. The results showed a significant correlation between incubation time, time until illumination and photobleaching. Furthermore, there was a significant correlation between photobleaching and erythema and also between photobleaching and pain. In conclusion, shorter PDT regimens result in decreased photobleaching and also less inflammation and pain. We hypothesize that a shorter incubation time is important for the optimal specific subcellular distribution of PpIX and to avoid unspecific distribution. We propose a shorter PDT regimen, "Pulse PDT", comprising, for example 30 min incubation with MAL and illumination after 180 min, and we have planned a study of actinic keratosis and "Pulse PDT".

Complex difference constrained compressed sensing reconstruction for accelerated PRF thermometry with application to MRI-induced RF heating.

PURPOSE: Introduce a novel compressed sensing reconstruction method to accelerate proton resonance frequency shift temperature imaging for MRI-induced radiofrequency heating evaluation. METHODS: A compressed sensing approach that exploits sparsity of the complex difference between postheating and baseline images is proposed to accelerate proton resonance frequency temperature mapping. The method exploits the intra-image and inter-image correlations to promote sparsity and remove shared aliasing artifacts. Validations were performed on simulations and retrospectively undersampled data acquired in ex vivo and in vivo studies by comparing performance with previously published techniques. RESULTS: The proposed complex difference constrained compressed sensing reconstruction method improved the reconstruction of smooth and local proton resonance frequency temperature change images compared to various available reconstruction methods in a simulation study, a retrospective study with heating of a human forearm in vivo, and a retrospective study with heating of a sample of beef ex vivo. CONCLUSION: Complex difference based compressed sensing with utilization of a fully sampled baseline image improves the reconstruction accuracy for accelerated proton resonance frequency thermometry. It can be used to improve the volumetric coverage and temporal resolution in evaluation of radiofrequency heating due to MRI, and may help facilitate and validate temperature-based methods for safety assurance.

Measurement of SAR-induced temperature increase in a phantom and in vivo with comparison to numerical simulation.

PURPOSE: To compare numerically simulated and experimentally measured temperature increase due to specific energy absorption rate from radiofrequency fields. METHODS: Temperature increase induced in both a phantom and in the human forearm when driving an adjacent circular surface coil was mapped using the proton resonance frequency shift technique of magnetic resonance thermography. The phantom and forearm were also modeled from magnetic resonance image data, and both specific energy absorption rate and temperature change as induced by the same coil were simulated numerically. RESULTS: The simulated and measured temperature increase distributions were generally in good agreement for the phantom. The relative distributions for the human forearm were very similar, with the simulations giving maximum temperature increase about 25% higher than measured. CONCLUSION: Although a number of parameters and uncertainties are involved, it should be possible to use numerical simulations to produce reasonably accurate and conservative estimates of temperature distribution to ensure safety in magnetic resonance imaging. R01 EB006563

Electromagnetic effects on forearm disuse osteopenia: a randomized, double-blind, sham-controlled study.

A randomized, double-blind, sham-controlled, feasibility and dosing study was undertaken to determine if a common pulsing electromagnetic field (PEMF) treatment could moderate the substantial osteopenia that occurs after forearm disuse. Ninety-nine subjects were randomized into four groups after a distal radius fracture, or carpal surgery requiring immobilization in a cast. Active or identical sham PEMF transducers were worn on the distal forearm for 1, 2, or 4 h/day for 8 weeks starting after cast removal ("baseline") when bone density continues to decline. Bone mineral density (BMD) and bone geometry were measured in the distal forearm by dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) at entry ("baseline") and 8, 16, and 24 weeks later. Significant average BMD losses after baseline were observed in the affected forearm at all time points (5-7% distally and 3-4% for the radius/ulna shaft). However, after adjusting for age, gender, and baseline BMD there was no evidence of a positive effect of active versus sham PEMF treatment on bone loss by DXA or pQCT for subjects completing all visits (n = 82, ∼20 per group) and for an intent-to-treat analysis (n = 99). Regardless of PEMF exposure, serum bone-specific alkaline phosphatase (BSAP) was normal at baseline and 8 weeks, while serum c-terminal collagen teleopeptide (CTX-1) was markedly elevated at baseline and less so at 8 weeks. Although there was substantial variability in disuse osteopenia, these results suggested that the particular PEMF waveform and durations applied did not affect the continuing substantial disuse bone loss in these subjects.

Reproducibility and expression of skin biomarkers in sun-damaged skin and actinic keratoses.

OBJECTIVES: To explore p53 and proliferating cell nuclear antigen (PCNA) expression and polyamine content as biomarkers in skin cancer chemoprevention trials, we evaluated their expression in early stages of UV-induced squamous cell tumorigenesis. METHODS: Biopsies were collected from three groups: 78 subjects with sun damage on forearms, 33 with actinic keratosis (AK) on forearms, and 32 with previous squamous cell carcinoma. Participants with sun damage were randomized to sunscreen or no sunscreen. RESULTS: We found significant differences in p53 and polyamines in forearms from the sun-damaged group (11.5 +/- 1.2% for p53, 65.5 +/- 1.9 nmol/g for putrescine, and 187.7 +/- 3.3 nmol/g for spermidine) compared with the group with sun damage plus AK (20.9 +/- 2.3% for p53, P = 0.0001; 81.7 +/- 3.9 nmol/g for putrescine, P = 0.0001; 209.4 +/- 8.2 nmol/g for spermidine, P < 0.06). PCNA was not different. When lesion histology was considered, there was a stepwise significant increase in p53 in biopsies without characteristics of AK compared with early AK (P = 0.02) and AK (P = 0.0006) and a similar pattern for PCNA with the only significant difference between early AK and AK. There was a stepwise increase in putrescine and spermidine in normal, sun-damaged forearm, forearm from subjects with AK, and the AK lesion itself (P < 0.0001). No significant differences in p53 or polyamines were seen in 3-month biopsies or, as a result of sunscreen use, although PCNA in the sun-damaged group not using sunscreen decreased significantly. CONCLUSIONS: p53 expression and polyamines in skin were elevated in early stages of skin tumorigenesis and were not affected by sunscreen, adding validity to their use as biomarkers in skin cancer chemoprevention trials.

[Restoration of function by microsurgical reconstruction after sarcoma excision in the upper limb]. / Funktionserhalt durch mikrochirurgische Rekonstruktion nach Sarkomresektion an der oberen Extremität.

The treatment of soft tissue sarcomas includes different modalities, but the complete excision of the tumor is the most important one. It is often difficult to resect the tumor completely and simultaneously restore a good function of the upper limb. Therefore a microsurgical reconstruction is often necessary as demonstrated here.

TMS motor cortical brain mapping in patients with complex regional pain syndrome type I.

OBJECTIVE: The motor cortical representation in patients with complex regional pain syndrome type I (CRPS I) was determined under the assumption that the motor cortex undergoes representational adaptations in the course of CRPS. METHODS: A total of 14 patients with CRPS I and a group of healthy subjects without any known neurological symptoms participated in the study. The motor cortical representation, i.e. the size of representation (cm2), motor-evoked potentials (MEP), the calculated volume (cm2 mV), and the center of gravity (CoG) were measured by transcranial magnetic stimulation. Recordings were made of the long extensor muscles of the forearm of the affected and unaffected hand. RESULTS: Analyses of the results revealed a significant asymmetry between the two hemispheres: the motor cortical representation corresponding to the unaffected hand was significantly larger. While the CoG data did not differ statistically between the two hemispheres, the CoG coordinates corresponding to the affected hand indicated a larger variability. CONCLUSIONS: The presence of pain and other CRPS symptoms may induce lasting changes in motor cortical plasticity, as it also does in the sensory cortex. SIGNIFICANCE: This could be of importance in rehabilitative strategies for the sensory motor system in CRPS I patients.

Local heating of human skin by millimeter waves: effect of blood flow.

We investigated the influence of blood perfusion on local heating of the forearm and middle finger skin following 42.25 GHz exposure with an open ended waveguide (WG) and with a YAV mm wave therapeutic device. Both sources had bell-shaped distributions of the incident power density (IPD) with peak intensities of 208 and 55 mW/cm(2), respectively. Blood perfusion was changed in two ways: by blood flow occlusion and by externally applied vasodilator (nonivamide/nicoboxil) cream to the skin. For thermal modeling, we used the bioheat transfer equation (BHTE) and the hybrid bioheat equation (HBHE) which combines the BHTE and the scalar effective thermal conductivity equation (ETCE). Under normal conditions with the 208 mW/cm(2) exposure, the cutaneous temperature elevation (DeltaT) in the finger (2.5 +/- 0.3 degrees C) having higher blood flow was notably smaller than the cutaneous DeltaT in the forearm (4.7 +/- 0.4 degrees C). However, heating of the forearm and finger skin with blood flow occluded was the same, indicating that the thermal conductivity of tissue in the absence of blood flow at both locations was also the same. The BHTE accurately predicted local hyperthermia in the forearm only at low blood flow. The HBHE made accurate predictions at both low and high perfusion rates. The relationship between blood flow and the effective thermal conductivity (k(eff)) was found to be linear. The heat dissipating effect of higher perfusion was mostly due to an apparent increase in k(eff). It was shown that mm wave exposure could result in steady state heating of tissue layers located much deeper than the penetration depth (0.56 mm). The surface DeltaT and heat penetration into tissue increased with enlarging the irradiating beam area and with increasing exposure duration. Thus, mm waves at sufficient intensities could thermally affect thermo-sensitive structures located in the skin and underlying tissue.

TMS-responses during anticipatory postural adjustment in bimanual unloading in humans.

Transcranial magnetic brain stimulation (TMS) was used to assess the influence of the corticospinal system on motor output during forearm unloading in humans. Unloading was obtained either "passively" by the experimenter, or "actively" with the subjects' own contralateral arm. Anticipatory postural adjustments consisted of changes in the activity of a forearm flexor muscle prior to active unloading of the limb and acted to stabilize the forearm position. Motor evoked potentials (MEPs) were recorded in the forearm flexor at different times during active and passive unloading, static forearm loading, and during lifting of an equivalent weight by the contralateral arm while the ipsilateral forearm was statically loaded and held stationary. In active unloading, MEP amplitude decreased with the decrease of muscle activity. Passive unloading resulted in a similar decrease of MEP as with active unloading. During stationary forearm loading, the change in MEP corresponded to the degree of loading. If during static loading the contralateral arm has lifted a separate, equivalent weight, the amplitude of MEP decreased. A possible role of direct corticospinal volley and the motor command mediated by subcortical structures in anticipatory postural adjustments is discussed.

A comparison of narrowband (TL-01) UVB-induced erythemal response at different body sites.

In most dermatology centres where phototesting is performed, the starting dose is calculated as a proportion of the minimal erythema dose (MED). Previous studies have found significant differences in MED readings between forearm and back skin with both broadband and narrowband (NB) UVB. Our objective was to compare MEDs obtained from three body sites, the forearm, back and abdomen, to see if there was a significant difference in individuals. We recruited 20 healthy volunteers who were exposed to our standard dose series for phototesting with NB-UVB to three body sites: forearm, back and abdomen. MEDs were assessed 24 h post exposure. The median MED for the abdomen was 0.79 J/cm2, the back 0.95 J/cm2 and the arm 1.11 J/cm2. Friedman's analysis of variance by ranks showed that these differences were significant (P = 0.003). There was no correlation between skin type and MED for any of the three anatomical sites. Our results support phototesting for all patients prior to treatment with NB-UVB. Furthermore, we have shown that the abdomen is the anatomical site of choice for phototesting, as this will result in a reduced risk of burning episodes.

Focal fibrocartilaginous dysplasia in the upper limb: seven additional cases.

Focal fibrocartilaginous dysplasia is a benign bone lesion known to cause deformity around the knee in young children. Three cases affecting the long bones of the upper limb have been reported, and little is known of the natural history. This study reports seven more cases affecting the upper extremity. All patients presented with deformity in early childhood. The location was the radius in two, the ulna in three, the proximal phalanx in one, and the middle phalanx in one. The radiographic appearance of the condition is diagnostic, regardless of the bone it affects. Proportional shortening of the affected segment was present in all patients. The phalangeal cases had marked deformity and were osteotomized, with early recurrence of the deformity in one case. The forearm lesions did not all resolve spontaneously. In the two patients with 7-year follow-up, the length discrepancy increased from 0.5 cm to 2 cm and a degree of cosmetic deformity remained, without functional impairment. Ulna lesions place the radiocapitellar joint at risk for dislocation and should be observed for this complication.

Influence of vehicle resistance on transdermal iontophoretic delivery of acetylcholine and sodium nitroprusside in humans.

Iontophoresis is a valuable method of noninvasive drug delivery for assessment of skin microvascular function, but it is important to consider and minimize its potential nonspecific electrical effects on blood flow. The use of sodium chloride (NaCl) instead of water as the iontophoresis vehicle has been reported to reduce these effects because it has a lower electrical resistance. However, this argument may not be valid when an agonist is added to the vehicle because its resistance will be changed. The aim of our study was to determine whether there is a difference in resistance between water and NaCl when used as vehicles for iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Four cumulative doses of each drug, dissolved in either water or NaCl, were delivered via iontophoresis to the forearm skin of 14 healthy volunteers. We measured the resulting blood flow responses by using laser-Doppler imaging and the voltage across the electrodes for each delivery as an index of resistance. For ACh and SNP, there were no significant differences between the voltages measured when either water or NaCl was used as the vehicle. However, the blood flow responses to both agonists were significantly lower with NaCl (ACh: 25% lower, P < 0.001; SNP: 15% lower, P = 0.019). The use of NaCl is therefore unlikely to decrease any nonspecific electrical effects, and it may in fact reduce the effective dose of drug delivered. Deionized water is a better iontophoresis vehicle for the assessment of microvascular function in skin when using ACh and SNP.

Effects of blood flow on skin heating induced by millimeter wave irradiation in humans.

We have previously reported species differences in the rate of skin heating in response to millimeter wavelength microwave exposure. We hypothesized that these differences were predominantly a function of species differences in the ability to increase skin blood flow during local heating. Mathematical modeling also suggested that, in humans, the rate of skin heating during prolonged millimeter wavelength exposure would be dependent on skin blood flow. In order to empirically test this hypothesis, we determined the role of baseline skin blood flow on the rate of cutaneous heating induced by 94-GHz microwave energy in humans (3 female, 3 male) using infrared thermography and laser Doppler imaging to measure skin temperature and relative skin blood flow, respectively. Millimeter wavelength exposure intensities used were high power (HP), 1 W x cm(-2) for 4 s and low power, 175 mW cm(-2) for 180 s. Skin blood flow was (a) normal, (b) eliminated using a blood pressure cuff to occlude forearm blood flow, or (c) elevated by heating the skin prior to irradiation. Results showed that for the HP exposures, these manipulations did not influence the rate of skin heating. For the low power exposures, occlusion of baseline skin blood flow had a small impact on the subsequent rate of heating. In contrast, a two-fold elevation in baseline skin blood flow had a profound impact on the subsequent rate of heating, resulting in a substantially lower rate of heating. Occlusion of an elevated skin blood flow reversed this lower rate of heating. The results of these studies demonstrate that relatively small changes in skin blood flow may produce substantial alterations in the rate of skin heating during prolonged 94-GHz exposure.

Electrosensibility and electromagnetic hypersensitivity.

Electromagnetic sensibility, the ability to perceive electric and electromagnetic exposure, and electromagnetic hypersensitivity (EHS), developing health symptoms due to exposure to environmental electromagnetic fields, need to be distinguished. Increased electrosensibility is a necessary, however, not a sufficient condition for electromagnetic hypersensitivity. At an extended sample of the general population of 708 adults, including 349 men and 359 women aged between 17 and 60 years, electrosensibility was investigated and characterized by perception threshold and its standard deviation. By analyzing the probability distributions of the perception threshold of electric 50 Hz currents, evidence could be found for the existence of a subgroup of people with significantly increased electrosensibility (hypersensibility) who as a group could be differentiated from the general population. The presented data show that the variation of the electrosensibility among the general population is significantly larger than has yet been estimated by nonionizing radiation protection bodies, but much smaller than claimed by hypersensitivity self-aid groups. These quantitative results should contribute to a less emotional discussion of this problem. The investigation method presented, is capable of exclusion diagnostics for persons suffering from the hypersensitivity syndrome.