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It has been reported that when a grounded human is exposed to an electric field at power frequency, a short-circuit current flowing from the feet to the ground is proportional to the square of his or her height. The current, however, should also vary with the body surface area, that is, body shape, even in people with the same height. In the present study, we confirmed this hypothesis using an analytical solution derived from a semi-ellipsoidal model. The short-circuit currents were calculated for various numerical human body models in which the horizontal length of a voxel was varied from 1.8 to 3.0 mm, and the results for different body shapes were compared. Finally, we derived an approximate expression for estimating the short-circuit current from the left-right width (2b), frontal thickness (2c), and height (a) of a human from the analytical solution. The short-circuit currents obtained from the approximate expression are consistent with those obtained from numerical calculations for 48 differently shaped human body models with a correlation coefficient of 0.9942. Hence, we concluded that the short-circuit current can be determined depending on the similarity ratio (a/b) and the ellipticity ratio (c/b) of the human body as well as the height. This finding is consistent with the numerical human body models that have been used previously, in which the similarity and ellipticity ratios were very close. Therefore, we can make the limited conclusion that the short-circuit current is proportional only to the square of the height. Additionally, numerical calculations showed that the short-circuit current is the same whether one foot or both feet are grounded.

Gel nails are a common artificial nail option. Ultraviolet (UV) nail lamps are commonly used to cure gel nails. Ultraviolet A radiation is a known mutagen that penetrates into the nail bed. Although previously reported, the role of UV nail lamps in the carcinogenesis of both keratinocyte carcinoma and melanoma remains controversial. Herein, we report a patient taking the photosensitizing agent hydrochlorothiazide who developed numerous squamous cell carcinomas on the dorsal hands and feet with a 10-year history of UV nail light exposure every 2-3 weeks.

Aims: The aim of this study was to quantify the risk of developing cancer from the exposure to radiation associated with surgery to correct limb deformities in children., Patients and Methods: A total of 35 children were studied. There were 19 girls and 16 boys. Their mean age was 11.9 years (2 to 18) at the time of surgery. Details of the radiological examinations were recorded during gradual correction using a Taylor Spatial Frame. The dose area product for each radiograph was obtained from the Computerised Radiology Information System database. The effective dose in millisieverts (mSv) was calculated using conversion coefficients for the anatomical area. The lifetime risk of developing cancer was calculated using government-approved Health Protection Agency reports, accounting for the age and gender of the child., Results: Correction was undertaken in five femurs, 18 tibiae, and 12 feet. The median duration of treatment was 45 months (11 to 118). The mean effective dose was 0.31 mSv (0.05 to 0.64) for the femur, 0.29 mSv (0.01 to 0.97) for the tibia, and 0.027 mSv (0.001 to 0.161) for the foot. The cumulative exposure gave 'negligible' risk in 26 children and 'minimal' risk in nine children, according to Public Health England categories. These results are below the mean annual background radiation in the United Kingdom., Conclusion: The lifetime attributable risk of developing cancer from repeated exposure to radiation was negligible or minimal in all children. This is the first study to quantify the exposure to radiation from serial radiographs in children with limb deformities who are treated surgically using circular external fixation, linking this to the risk of developing cancer. Cite this article: Bone Joint J 2019;101-B:241-245.

A 41-year-old man with gastric adenocarcinoma presented with hepatic metastases. The metastases were refractory to systemic chemotherapy, so radioembolization with Y microspheres was performed. Because of stasis or saturation of the tumor with embolic particles, 79% of the microspheres were injected. At follow-up, the patient complained of "red bumps" that had developed on his right foot/ankle the day after the radioembolization. Because a portion of the dose was still in the catheter when withdrawn from the right femoral artery, the interventional radiologist used a Geiger counter to confirm radioactivity in the cutaneous lesions and thus the distal embolization of the microspheres.

Low-level laser therapy (LLLT) has been suggested as a resource capable of increasing resistance to fatigue and enhancing muscle performance through its metabolic and photochemical effects. This study evaluated the immediate effects of the application of LLLT on neuromuscular performance of the plantar ankle flexors in healthy subjects through a fatigue-induced protocol. This is a randomized controlled clinical trial, attended by 60 young and physically active volunteers of both genders. The subjects were randomly assigned into three groups, control, placebo, and laser, and underwent a preliminary evaluation of the isokinetic performance of plantar flexors and electromyographic activity of the soleus muscle to ensure homogeneity between groups. After the application of the respective intervention protocols, participants were induced to fatigue by performing 100 isokinetic concentric contractions of ankle plantar flexors at a speed of 90°/s. The dynamometric fatigue index (DFI) and median frequency were recorded during the fatigue protocol for comparison between groups. The group receiving the laser application showed significantly lower dynamometric fatigue index (p = 0.036) when compared to control and placebo groups. In relation to the median frequency during the fatigue test, there was a decrease in all groups, however with no differences between them. We suggest that LLLT being applied prior to exercise can reduce the fatigue index in the ankle plantar flexors of healthy subjects.

Background: Soft-tissue sarcomas (STS) of the distal extremities are a rare disease entity, hence proper treatment strategy is not well established. We evaluated the local control, survival and complications of treating sarcomas in the wrist, hand, ankle and foot with limb-sparing surgery (LSS) and postoperative radiotherapy (PORT)., Patients and Methods: Seventeen patients with STS in wrist, hand, ankle and foot who received PORT after LSS from August 2008 to November 2015 were retrospectively reviewed. Primary outcome was 5-year local recurrence-free survival (LRFS). Secondary outcomes were 5-year distant metastasis-free survival (DMFS) and toxicities., Results: The median age was 32 (range=12-78) years. The most frequent STS location was the foot in 11 patients (64%) followed by two patients each in the wrist, hand and ankle, respectively. Fourteen patients (82%) underwent wide resection with flap grafts and the same number of patients achieved clear resection margins. The median postoperative radiation dose was 54 (range=46-60) Gy. Five patients also received chemotherapy. At a median follow-up of 39 (range=6-87) months, 5-year LRFS and DMFS were both 100%. Only one patient experienced grade 3 radiation dermatitis and there was no major wound complication. Radiation-induced bone fracture occurred in two patients., Conclusion: PORT after LSS showed excellent local control for STS in the wrist, hand, ankle and foot. Considering the good local control and saving of limb function without any significant toxicity, the combination of LSS followed by PORT could be an appropriate and safe modality for STS of the distal extremities., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

It is 40 years ago that a very popular X-ray device disappeared in German shoe shops: the shoe-fitting fluoroscope or Pedoskop. Since the 1930s, these X-ray machines were an integral part of any good shoe business. Following the entry into force X-Ray Regulation (RöV 1973) the use of these devices was prohibited in Germany., (Copyright © 2014. Published by Elsevier GmbH.)

The increase in PGE2 production by microsomal PGE synthase-1 (mPGES-1) in CNS contributes to the severity of the inflammatory and pain responses in the model of edema formation and hyperalgesia induced by carrageenan. PGI2, alike to PGE2, plays an important role in the inflammation. Low-level laser therapy (LLLT) has been used in the treatment of inflammatory pathologies, reducing both pain and the acute inflammatory process. In this work, we studied the effect of LLLT on the expression of both mPGES-1 and IP messenger RNA (mRNA), in either subplantar or total brain tissues obtained from rats submitted to model of edema formation and hyperalgesia induced by carrageenan administration. The test sample consisted of 30 rats divided into five groups: A1 (control-saline), A2 (carrageenan-0.5 mg/paw), A3 (carrageenan-0.5 mg/paw + LLLT), A4 (carrageenan-1.0 mg/paw), and A5 (carrageenan-1.0 mg/paw + LLLT). The animals from groups A3 and A5 were irradiated 1 h after induction of inflammation by carrageenan injection. Continuous-wave red laser with wavelengths of 660 nm and dose of 7.5 J/cm(2) was used. Six hours after carrageenan-induced inflammation, mPGES-1 and prostacyclin receptor (IP) mRNA expression were significantly increased both in subplantar and brain tissues. LLLT was able to reduce both mPGES-1 and IP mRNA expression in subplantar and brain tissues. We suggest that LLLT is able to reduce both inflammation and hyperalgesia observed in the model of edema formation and hyperalgesia induced by carrageenan, by a mechanism involving the decrease in the expression of both mPGES-1 and IP.

This is a proof-of-concept study demonstrating the capacity for modulated electron radiation therapy (MERT) dose distributions using 3D printed bolus. Previous reports have involved bolus design using an electron pencil beam model and fabrication using a milling machine. In this study, an in-house algorithm is presented that optimizes the dose distribution with regard to dose coverage, conformity, and homogeneity within the planning target volume (PTV). The algorithm takes advantage of a commercial electron Monte Carlo dose calculation and uses the calculated result as input. Distances along ray lines from the distal side of 90% isodose line to distal surface of the PTV are used to estimate the bolus thickness. Inhomogeneities within the calculation volume are accounted for using the coefficient of equivalent thickness method. Several regional modulation operators are applied to improve the dose coverage and uniformity. The process is iterated (usually twice) until an acceptable MERT plan is realized, and the final bolus is printed using solid polylactic acid. The method is evaluated with regular geometric phantoms, anthropomorphic phantoms, and a clinical rhabdomyosarcoma pediatric case. In all cases the dose conformity are improved compared to that with uniform bolus. For geometric phantoms with air or bone inhomogeneities, the dose homogeneity is markedly improved. The actual printed boluses conform well to the surface of complex anthropomorphic phantoms. The correspondence of the dose distribution between the calculated synthetic bolus and the actual manufactured bolus is shown. For the rhabdomyosarcoma patient, the MERT plan yields a reduction of mean dose by 38.2% in left kidney relative to uniform bolus. MERT using 3D printed bolus appears to be a practical, low-cost approach to generating optimized bolus for electron therapy. The method is effective in improving conformity of the prescription isodose surface and in sparing immediately adjacent normal tissues.

Objective: The purpose of this study was to evaluate the influence of monochromatic infrared energy (MIRE) on the microcirculation of the skin surface of the feet in healthy subjects., Background Data: Near-infrared energy was shown to increase microcirculation in an animal study. In humans, only one case study demonstrated that MIRE increases microcirculation in the skin of the lower limbs., Methods: Thirty healthy volunteers were recruited and randomly allocated into three groups to receive either: (1) active MIRE; (2) sham MIRE (placebo group); or (3) warm packs (control group) on the feet. The MIRE device comprised an array of 60 x 890 nm LEDs attached to flexible pads (3×7.5 cm). Each diode spot size was 0.2 cm(2), and each LED power was 12 mW with a power density of 60 mW/cm(2). The arrays were placed in direct contact with the skin for 30 min delivering a total fluence of 108 J/cm(2) over an area of 22.5 cm(2). Capillary blood cell velocity (CBV) and superficial skin blood flow (flux) were recorded before and after intervention., Results: Significant differences among the three groups were recorded in both CBV and flux (both p<0.05). Post-hoc comparisons indicated that a significantly greater increase in both CBV and flux occurred in the active MIRE group than in the placebo group and control group (all p<0.05)., Conclusions: A 30-min MIRE produced a significantly greater increase in the CBV and flux of the feet in the active MIRE group than in the placebo and control groups.

The purpose of this study was to determine if NO blood concentrations increased acutely following an 8-week course of pulsed infrared light therapy (PILT) which could be linked to an improvement in peripheral protective sensation (PPS) in patients who have profound chronic diabetic peripheral neuropathy. A total of 22 subjects with the diagnosis of type 1 (N = 2) or type 2 (N = 20) diabetes participated in the study. PILT was administered to one foot chosen at random with the other foot serving as a within-subject control (no treatment). Patients underwent 24 treatments (3 times/week, for 8 weeks) for 30 min per treatment. Venous blood samples were taken during the last 5 min of treatment from veins in the dorsum of the control and experimental feet and were later analyzed for NO concentration. Contrary to the popular supposition, PILT treatments actually resulted in a significantly (P < 0.05) decreased concentration of NO. Additionally, there were no significant differences between the treated and untreated feet. Since in individuals where PILT has significantly improved PPS, PILT did not stimulate an increased NO content in the blood, it appears that infrared light improves peripheral protective sensation in patients by a mechanism other than an increased NO production.

Background: Increasing experimental and clinical evidence suggests that illumination of the skin with relatively low intensity light may lead to therapeutic results such as reduced pain or improved wound healing. The goal of this study was to evaluate prospectively whether socks made from polyethylene terephthalate (PET) incorporating optically active particles (Celliant) ameliorates chronic foot pain resulting from diabetic neuropathy or other disorders. Such optically modified fiber is thought to modify the illumination of the skin in the visible and infrared portions of the spectrum, and consequently reduce pain., Methods: A double-blind, randomized trial with 55 subjects (38 men, 17 women) enrolled (average age 59.7 +/- 11.9 years), 26 with diabetic neuropathy and 29 with other pain etiologies. Subjects twice completed the Visual Analogue Scale (VAS), Brief Pain Inventory (BPI), McGill Pain Questionnaire (MPQ), and SF-36 a week apart (W(1+2)) before receiving either control or Celliant socks. The same questionnaires were answered again one and two weeks (W(3+4)) later. The questionnaires provided nine scores for analyzing pain reduction: one VAS score, two BPI scores, five MPQ scores, and the bodily pain score on the SF-36. Mean W(1+2) and W(3+4) scores were compared to measure pain reduction., Results: More pain reduction was reported by Celliant subjects for 8 of the 9 pain questions employed, with a significant (p = 0.043) difference between controls and Celliant for McGill question III. In neuropathic subjects, Celliant caused more pain reduction in 6 of the 9 questions, but not significantly. In non-neuropathic subjects 8 of 9 questions showed more pain reduction with the Celliant socks., Conclusion: Socks with optically modified PET (Celliant) appear to have a beneficial impact on chronic foot pain. The mechanism could be related to the effects seen with illumination of tissues with visible and infrared light., Trial Registration: ClinicalTrials.gov NCT00458497.

There are several reports of altered pain sensation after exposure (from a few minutes to hours in single or repeated doses for 2-3 weeks) to electromagnetic fields (EMF) in adults. The commonly utilized noxious stimulus is radiant heat. The nociceptive responses are known to be influenced by characteristics of stimulus, organism, and environment. We studied the pattern of nociceptive responses to various noxious stimuli in growing rats exposed to radiofrequency field (73.5 MHz amplitude modulated, 16 Hz power density 1.33 mw/cm(2), SAR = 0.4 w/kg) for 45 d (2 h/d). Threshold current for stimulation of nociceptive afferents to mediate motor response of tail (TF), vocalization during stimulus (VD), and vocalization after discharge (VA); the withdrawal latency of tail (TFL) and hind paw (HPL) to thermal noxious stimulus and tonic pain responses were recorded in every rat. The TFL was not affected, HPL was decreased (p < 0.01), and the thresholds of TF and VD were not affected, while, that of VA was significantly decreased. The tonic pain rating was decreased (p < 0.01). A decrease in the threshold of VA (p < 0.01) is indicative of an increase in the emotional component of the response to the phasic pain, whereas a decrease in the pain rating indicates analgesia in response to the tonic pain. The results of our study suggest that chronic (45 d), intermittent (2 h/d) amplitude modulated RF field exposure to the peripubertal rat increases the emotional component of phasic pain over a basal eaualgesic state, while late response to tonic pain is decreased. The data suggest that amplitude modulated RF field differentially affects the mechanisms involved in the processing of various noxious stimuli.

Change of impulse activity in branches of n. saphenus caused by influence of linearly polarized light with various wave lengths on the skin of rat's hind limb was studied. It was established that polarized light effect on skin receptor endings depended on wave length. Exposure of skin to red and blue parts of spectrum increased afferent impulsing of peripheral nerve for a short time, and influence of polychromatic polarized light (400-2000 nm) significantly decreased it for a long time (like lidocaine effect).

Basal cell carcinoma of the sole is very rare. This report describes an occurrence in which a basal cell carcinoma may have developed in relation to radiation exposure from a shoe-fitting fluoroscope. The obvious limitation is that there is no record or means to measure any amount of radiation that a person may have received from this primitive fluoroscope. We conclude that radiation very likely did induce this lesion in this individual.

The noradrenergic nucleus locus coeruleus (LC) has a direct projection to the basal lateral amygdala (BLA). Behavioral, lesion and pharmacological studies suggest that this pathway has an important role in mediating responses to emotional stimuli and in the formation of long term memory. The effect of LC activation on the activity of BLA neurons in vivo is not known. Therefore, in the present experiments, simultaneous extracellular unit recordings were made in the two regions while the anesthetized rat received electrical stimulation of the paw to simulate a real-life acute stressor, commonly used as an aversive reinforcer in conditioning experiments. All LC neurons exhibited a multiphasic excitatory response followed by prolonged inhibition. Responses of BLA cells were more heterogeneous, but predominantly inhibitory, with a release from inhibition during the refractory phase of LC. Direct electrical stimulation of the LC with a single pulse also elicited an inhibitory response in BLA. BLA response to both footshock and LC stimulation was partially blocked by the beta adrenergic receptor antagonist, timolol, infused into the BLA. These experiments are the first to report in vivo effects of activation of the noradrenergic system on neuronal activity in the BLA.

In treatment planning for hadron therapy, information about the relative stopping power in a patient's body is used to calculate the range of incident ions. This information is obtained from computed tomography (CT) images using a conversion table from x-ray CT numbers into stopping powers relative to the stopping power of water. In treatment planning at the National Institute of Radiological Sciences (NIRS), the conversion table has been created based on the polybinary tissue model. However, it has not been fully verified that the model is accurate enough for use in real animal tissues. In order to irradiate heavy ions more precisely in radiotherapy, we have to evaluate the accuracy of the polybinary tissue calibration in animal tissues. We have measured animal tissue samples with a heavy-ion CT (HICT) and an x-ray CT. The x-ray CT image was converted to an image of relative stopping power by using the table derived from the polybinary tissue calibration (polybinary-tissue-model CT (PTCT) image). On the other hand, with HICT, the two-dimensional distribution of relative stopping power can be obtained directly. A comparison between PTCT and HICT images enabled us to verify the accuracy of the conversion table derived from the polybinary tissue calibration. Consequently, it was found that the agreement between the relative stopping powers of PTCT and HICT is 1.6% for fat, muscle and bone.

Background: The basolateral complex (BLA) and the central nucleus of the amygdala (CeA) are believed to mediate the expression of affective responses. After affective learning, conditioned stimulus-related information is thought to be conveyed from the BLA to the CeA; the medial CeA (Cem), in turn, projects to hypothalamic and brainstem structures involved with induction of affective responses. Although the conditioned stimulus and unconditioned stimulus both evoke affective responses, the precise response often differs. It is unknown whether this difference is represented by distinct activity patterns of single Cem neurons. Furthermore, the nature of the interaction between the BLA and Cem is unknown., Methods: Using in vivo extracellular and intracellular recordings, we examined how the BLA affects the Cem and compared this with effects induced by footshock (unconditioned stimulus) in the same neurons., Results: Our results demonstrate that, contrary to conventional views, BLA stimulation primarily inhibits Cem neurons by a polysynaptic circuit, and show that single Cem neurons respond to both BLA input and footshock in an opposite manner., Conclusions: These results demonstrate the predominantly inhibitory nature of the BLA-Cem interaction. These data further demonstrate the distinct cellular events that might lead to differential modulation of conditioned and unconditioned affective responses.

Background: According to clinical studies, the stimulation of acupuncture points (APs) by a variety of methods (eg, needles, pressure, etc) is an effective method for the treatment of many pain syndromes. However, no experimental proof exists showing that the exposure of APs to low-intensity incoherent polarized (P) light evokes an analgesic affect., Objectives: The authors' previous work, using mice, shows that the exposure of APs to low-intensity microwaves effectively decreases pain. The purpose of the present study was to determine whether exposure of APs to low-intensity incoherent P light evokes a statistically significant reduction in pain., Methods: The effects of P light on behavioural responses to acute and tonic pain were tested in mice. The threshold of vocalization during electrical stimulation of the foot (acute pain) was measured before and after exposure of AP E-36 to P light. The duration of licking the formalin-injected foot (tonic pain) was investigated in control mice and mice exposed to P light on APs E-36, V-56 and V-60 or on skin that did not contain analgesic APs., Results: Exposure of APs to P light evoked a statistically significant increase in pain threshold by 34.2% to 59.1%, and shortened the licking time by 32.3% to 50% in mice. The most effective AP was E-36 in both the painful foot and the normal foot. After 2 min, 6 min and 10 min of P light exposure, analgesia was 7.6%, 30.9% and 50%, respectively. The exposure to P light on skin that did not contain analgesic APs did not evoke significant effect., Conclusions: The results show the efficacy of pain suppression by exposure of antinociceptive APs to P light.

The medical records of 2239 patients (mean age=73 years) with established peripheral neuropathy (PN) were examined to determine whether treatment with MIRE was, in fact, associated with increased foot sensitivity to the Semmes Weinstein monofilament (SWM) 5.07 and a reduction in neuropathic pain. The PN in 1395 of these patients (62%) was due to diabetes. Prior to treatment with MIRE, of the 10 tested sites (5 on each foot), 7.1+/-2.9 were insensitive to the SWM 5.07, and 2078 patients (93%) exhibited loss of protective sensation defined by Medicare as a loss of sensation at two or more sites on either foot. After treatment, the number of insensate sites on both feet decreased to 2.4+/-2.6, an improvement of 66%. Of the 2078 (93%) patients initially presenting with loss of protective sensation, 1106 (53%) no longer had loss of protective sensation after treatment (P<.0001); 1563 patients (70%) also exhibited neuropathic pain in addition to sensory impairment. Prior to treatment with MIRE, pain measured on the 11-point visual analogue scale (VAS) was 7.2+/-2.2 points, despite the use of a variety of pain-relieving therapeutic agents. After treatment with MIRE, pain was reduced by 4.8+/-2.4 points, a 67% reduction. Therefore, MIRE appears to be associated with significant clinical improvement in foot sensation and, simultaneously, a reduction in neuropathic pain in a large cohort of primarily Medicare aged, community-dwelling patients, initially diagnosed with PN. The quality of life associated with these two outcomes cannot be underappreciated.

Radiation safety was determined to maintain quality control in the cyclotron laboratory. Based on the results of 438 runs in the Faraday cup (20 microA for 10 min), 20 runs on 18O-water target (40 microA for 2 h) and 10 runs on 18O-gas targets (30 microA for 45 min), we have established that occupationally exposed workers remain 10 +/- 5 times below federal regulatory limits (FRLs) in the cyclotron vault, 30 +/- 8 times below FRL in the radiochemistry laboratory and 200 +/- 10 times below the FRL outside the cyclotron laboratory during beam operation. (The FRL for unrestricted area are <20 microSv in 1 h.) The non-occupationally exposed workers serving in offices in the vicinity of the cyclotron vault within 100 m distance remained 200 times below the FRL irrespective of beam being on or off, suggesting that routine beam operation of 40 microA for 2 h once a day during office hours is safe provided quality control and system performance measures as discussed in this report are strictly maintained.

Studies were undertaken to find out the effects of low frequency pulsed electromagnetic field (PEMF) in adjuvant induced arthritis (AIA) in rats, a widely used model for screening potential therapies for rheumatoid arthritis (RA). AIA was induced by an intradermal injection of a suspension of heat killed Mycobacterium tuberculosis (500 mug/0.1 ml) into the right hind paw of male Wistar rats. This resulted in swelling, loss of body weight, increase in paw volume as well as the activity of lysosomal enzymes viz., acid phosphatase, cathepsin D, and beta-glucuronidase and significant radiological and histological changes. PEMF therapy for arthritis involved optimization of three significant factors, viz., frequency, intensity, and duration; and the waveform used is sinusoidal. The use of factorial design in lieu of conventional method resulted in the development of an ideal combination of these factors. PEMF was applied using a Fransleau-Braunbeck coil system. A magnetic field of 5 Hz x 4 muT x 90 min was found to be optimal in lowering the paw edema volume and decreasing the activity of lysosomal enzymes. Soft tissue swelling was shown to be reduced as evidenced by radiology. Histological studies confirmed reduction in inflammatory cells infiltration, hyperplasia, and hypertrophy of cells lining synovial membrane. PEMF was also shown to have a membrane stabilizing action by significantly inhibiting the rate of release of beta-glucuronidase from lysosomal rich and sub-cellular fractions. The results indicated that PEMF could be developed as a potential therapy in the treatment of arthritis in humans., ((c) 2005 Wiley-Liss, Inc.)

Administration of 3 mg/kg 5-hydroxytryptamine2A/2C (5-HT2A/2C) receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) induced c-Fos expression in all areas of the rat neocortex. The single footshock 24 h before DOI administration significantly attenuated DOI-induced c-Fos expression in layer IV of the primary somatosensory cortex. These changes in c-Fos expression suggest an adaptational change in the somatosensory cortex by acute stress.

Background and Purpose: The validity of the assumption of equal biological effect with dose per fraction in fractionated radiotherapy has been examined for the acute skin reaction in a rat foot model using a variable number of 2-Gy daily fractions followed by graded top-up doses., Material and Methods: Mature female rats were used. Both hind feet of each rat were irradiated with a range of fractionated and top-up doses of 60Co gamma-rays. The dose-related incidence of moist desquamation was used as an end-point. Quantal data for the incidence of moist desquamation were analysed using probit analysis and ED50 (+/-SE) values were obtained. The results were also compared with predicted values obtained from the application LQ-model., Results: After a single 2-Gy fraction followed by top-up doses 24 h later, the dose effect curve for the top-up doses used was shifted to lower doses as expected and the ED50 for moist desquamation of 19.78 +/- 0.13 Gy was 1.16 Gy less than the ED50 of 20.94 +/- 0.15 Gy for large single dose exposure alone. This implied that only approximately 58% of the initial 2-Gy fraction was effective, and the rest was repaired within a 24-h interval between the 2 Gy and top-up doses. However, after two or three 2-Gy daily fractions the dose effect curves for the subsequent top-up doses moved to the higher doses again and the ED50 for top-up dose increased to 20.33 +/- 0.21 and 20.75 +/- 0.11 Gy, respectively. A further increase in the number of 2-Gy daily fractions shifted the dose effect curves for the top-up doses to lower doses and ED50 values for the top-up doses decreased progressively., Conclusions: The findings were not in keeping with values predicted based on the assumption of equal effect per fraction and could not be explained by the use of a single alpha/beta ratio in the LQ-model.

Aim: The aim of this work was to estimate the error in dose calculations, to check the agreement between the measured and calculated doses and to analyse dose discrepancies in the group of patients undergoing total body irradiation., Patients and Methods: A combination of lateral and anterior-posterior fields was used in 8 fractions and on 4 consecutive days. Doses were preliminarily calculated and then measured in vivo by thermoluminescent, semiconductor and ionization dosimeters attached to the body in 10 representative transverse cross-sections. Calculations and measurements were carried out for the beam at the body entry and exit. The error in dose calculations was estimated for each reference point. Dose deviations between calculations and measurements were analysed using the Student's t-test., Results: The error in preliminary dose calculations ranged from 3% to 15% (Table 1). Standard deviations of the measurements and percent deviations from the calculations exceeded 10% only for the lung and neck exits (Table 3). Average thermoluminescent readings were 6% higher than the corresponding semiconductor readings. The measured doses fitted the calculated values within the limit of error, except for the lung, head and neck exits for the whole group, depending on the type of fields used (Table 4).

Background: In the literature there is some evidence that the incidence of metastases may increase after radiation treatment., Methods: In order to investigate whether radiation-induced changes in the lymphatic drainage may alter the rate of lymph node metastasis, the center part of the left hind foot of rats was irradiated with a dose of 1 x 55 Gy before inoculation of tumor cells into the irradiated part of the footpad at different time intervals. Cells of 2 different tumor lines were employed. A rarely metastasising rhabdomyosarcoma, R-1, to look for a possible enhancement of lymphatic metastases, and a readily metastasising mammary carcinoma, Cl-2, in case of a possible decrease in the rate of lymphatic metastasis from tumors growing in pre-irradiated footpads., Results: The incidence of regional lymph node metastasis decreased for R-1 tumors growing in pre-irradiated footpads, but not for Cl-2 tumors. Furthermore, the average time required for lymph node metastasis to attain a reference volume of 100 mm3 is not significantly influenced by pre-irradiation of the footpad. No difference was observed in average times for doubling in volume of lymph node metastases originating from primary tumors in pre-irradiated footpads. Abscopal effects after footpad irradiation may cause a 50-fold increase in size of regional lymph nodes and, therefore, histological examination is essential for verification of lymph node metastases., Conclusions: Damage to the lymphatic system to be expected in the irradiated footpad did not enhance the incidence of regional metastasis of R-1 tumors. A reduced rate of lymphatic metastasis contradicts earlier findings of enhanced lymphatic metastasis development of R-1 tumors, growing in pre-irradiated gastrocnemius muscles. The influence of irradiation on regional metastasis formation seems to be "tumor bed" dependent for R-1 tumors.

Objective: This controlled experimental study was designed to compare the effects of a well-known NSAID, tenoxicam, with mid-laser irradiation on the inflammatory component of adjuvant-induced arthritis (AIA). Four groups of animals, each consisting of 10 Wistar rats, were included in the study. The primary concern was not to investigate the antiinflammatory effects of tenoxicam, but to compare the previously proven effects of this drug with a physical therapy agent which might be considered to have fewer side effects and/or contraindications., Method: The first group received only 0.1 ml of complete Freund's adjuvant (CFA) and served as the control for the other groups. The 2nd, 3rd and 4th groups, after having CFA injected into the plantar surfaces of their right paws, were treated with tenoxicam alone, mid-laser alone, or with a combination of the two, respectively., Results and Conclusion: All 3 groups showed significantly reduced paw edema compared with the control group. Although the reduction in paw edema in the animals treated with tenoxicam or with tenoxicam+ mid-laser was more significant, mid-laser is proposed as an alternative therapy for symptomatic relief in certain conditions well known to limit the use of NSAIDs.

Nucleolar organizer regions stained with colloidal silver techniques (AgNOR) evidence sites of active rRNA transcription. It has been proved that AgNOR undergo a rise in number and variations in size and shape in conditions which traditionally involve enhanced cell proliferation and rRNA transcription. AgNOR have been described as a marker of malignant transformation in multiple entities. Our laboratory has previously described their value as markers of radioinduced damage. The finding, at light microscopy level, that silver staining persisted at later post-irradiation times when cells are characteristically inactive, prompted the present study to correlate findings at light microscopy level with the ultrastructural analysis of nucleoli and their AgNOR in a model of irradiated skin. We herein attempt to explain the biological significance of AgNOR variations in the different phases of radioinduced response (which involves cellular hyperactivity followed by regressive features). Ten Wistar rats were submitted to local irradiation of the left leg (the shielded right leg was used as control) with 50 Gy x rays and killed 15 days post- irradiation. Silver staining was performed on ultrathin sections. In the basal layer of control epithelium silver affinity was established for fibrillar centers (FC) and fibrillar dense components (DFC). During the phase of radioinduced hyperplasia (1-3 days post-exposure) basal cells exhibit large reticular nucleoli, with irregular contours and silver staining on DFC. In the regressive phase (4-5 days post-irradiation) silver staining persists despite the halt in transcriptional activity, associated to homogeneous and compact nucleoli. These findings suggest caution in the interpretation of silver staining patterns.

Purpose: A patient with malignant melanoma on the left foot was treated by thermal neutron capture therapy using 10B-paraboronophenylalanine. We compared the actual (clinical) response with the predicted response estimated using our past experimental and clinical data, and discussed some problems to be overcome in the future., Materials and Methods: We adopted an intravenous drip infusion of the compound whereby 170 mg/kg of the drug was administered over 4-5 hours before neutron irradiation. The patient was then irradiated with thermal neutrons from the Musashi Reactor at a reactor power of 100 kW and a neutron flux of 1.0 x 10(9) n/cm2/s at the collimator surface. The total absorbed dose to the melanoma and the surrounding skin was calculated by multiplying the thermal neutron fluences by the conversion factor., Results: The total absorbed doses to the melanoma and the surrounding normal skin were calculated as 19.0 and 9.4 Gy, respectively. These absorbed doses were estimated at 33.5 and 14.2 RBE-Gy, respectively, assuming that the relative biological effectiveness (RBE) of the high LET radiations was 2.0 and that each component of the mixed radiation was simply additive. The melanoma showed marked regression with mild skin reaction (dry desquamation) a month after therapy, and finally disappeared 10 months after therapy. There were no no substantial side effects., Conclusion: We concluded that the outcome of our calculated dose values agreed well with the clinical response and that their compatibility indicated considerable validity for our approach. However, there are still some problems-uncertainty concerning the 10B concentration in tumor and skin, determination of the total absorbed dose, and a single curative dose for malignant melanoma-to be overcome with regard to clinical use of this therapy.

Radio frequency currents in the human body, induced by high-frequency and medium-frequency high-power broadcast antennas, were studied theoretically and experimentally. An analytical formula was derived to calculate the foot currents in a grounded semispheroidal model of the human body. The model agrees within 30% with the results given by the standard formula presented by Gandhi on the basis of measurements with humans. Near 100 kHz, the model predicts a decrease of 14% of the current dissipated in the human body, which is due to the beta relaxation of the cells. The effect of the body and foot-contact impedances were studied with the aid of a simplified equivalent circuit which showed that the body impedance does not considerably affect the foot current below 10 MHz. The normalized foot currents measured in front of the broadcast antennas were within 30% agreement of the currents calculated with the Gandhi formula from the electric fields measured at a height of 1 m. The foot currents are induced by vertical electric fields for both medium-frequency and high-frequency antennas in spite of a strong horizontal component in the latter case. The distance at which the occupational exposure limit of 200 mA was exceeded in the worst (maximum coupling) case was 50 m for the high-frequency antenna and < 14 m for the medium-frequency antenna. In the latter case, the radio frequency shocks resulting from touching ungrounded metallic bodies impose a practical limit to about 40 m.

This is a case of a young woman with a low grade malignant hemangioendothelioma of bone, who is considered cured after more than 8 years of follow-up post radiotherapy. This patient demonstrates that, despite the characteristic multifocality of this rare tumor, treatment with radiotherapy alone can be curative.

Thermal hyperalgesia was induced by UV irradiation of the glabrous skin of the hindpaw of adult female Sprague-Dawley rats. We have recorded single cell activity and studied excitability changes in wide dynamic range neurons in the lumbar spinal segments during the early phase (days 1-3) and late phase (days 5-7) of thermal hyperalgesia in animals under urethane anaesthesia. The proportion of spontaneously active wide dynamic range cells was increased following UV irradiation and the degree of spontaneous activity was enhanced during the course of hyperalgesia. In addition there was a significant increase in the total number of spikes evoked by standardized mechanical and noxious heat stimuli when tested at days 1-3 and days 5-7. The duration of the evoked responses was also significantly prolonged in both UV-treated groups. The noxious temperature threshold to radiant heat stimulation was significantly decreased on the UV-treated but not on the contralateral hindpaw. The average size of the receptive fields on the UV-treated paws was expanded in comparison to control. To differentiate between possible central and peripheral components of the hyperactivity of wide dynamic range cells we performed in situ dorsal rhizotomy during the recording. Cutting the dorsal roots (L2-5) evoked a significantly larger and more prolonged discharge in wide dynamic range cells in both UV-treated groups in comparison to control. Spontaneous activity in spinal wide dynamic range neurons was reduced after rhizotomy in each group. However, the decrease was only significant at days 1-3 (P < 0.05) but not at days 5-7.(ABSTRACT TRUNCATED AT 250 WORDS)

Our previous study on early- and late-appearing murine foot reactions following combined hyperthermia and irradiation suggested that hyperthermia may not inhibit repair of sublethal and/or potentially lethal radiation damage for the late-appearing reaction. A series of split dose experiments was performed by using C3Hf/Sed mouse foot reaction, which showed both early and late responses in the same tissue. Hyperthermia given in a 43.5 degrees C water bath for 45 min inhibited radiation damage repair in the early-appearing reaction, but was not able to modify repair in the late-appearing reaction. The failure of thermal inhibition of radiation damage repair in the late-appearing reaction was observed regardless of the sequence of heat and irradiation. Complete repair appeared to require approximately 9 hr. Although it is unknown whether radiation damage repair can be completely inhibited in all late-responding normal tissues, the reduction in thermal repair inhibition in some late-responding tissues may be an advantage of "heat prior to irradiation" treatment over radiation alone.

The effect of twice-a-day irradiation on the foot reaction was studied in C3Hf/Sed mice. A numerical scoring system was used to evaluate the foot reaction that became visible shortly after irradiation. Peak reaction occurred on the 21st to 23rd day and reappeared after approximately the 200th postirradiation day. These reactions are called early- and late-appearing reactions, respectively. Animals studied for early-appearing reactions were continuously scored for more than 600 days after irradiation. The late-appearing reaction increased continuously or remained constant, but never decreased during the course of the experiments. Animal feet were irradiated with a fraction size from 1.0 to 5.0 Gy twice-a-day daily with a treatment interval of 6 and 18 hours, and varying numbers of fractions were given. A top-up dose of 20 Gy was given as the last dose. The late-appearing foot reaction following a fraction size of 1.5 Gy or greater increased with increasing total dose. However, the increase in the late reaction score with increasing total dose was trivial following multiple doses with a fraction size of 1.0 Gy, suggesting a possible repopulation during prolonged irradiation or that the observed reaction was a consequential late effect. The Fe-plot based on doses which induced fibrosis in one-half of the irradiated animals, showed an alpha/beta ratio of 6.57 +/- 0.62 Gy, and the presence of a breaking point at approximately 1.5 Gy. The alpha/beta ratios calculated by Joiner's method and Thames direct analysis were identical. The slope of the Fe-plot below 1.5 Gy was significantly steeper than that above 1.5 Gy.

To study the effect of multiple daily fractions on acute murine foot reaction, the left feet of C3Hf/Sed mice were irradiated by a Cs-137 irradiator at intervals of 6 and 18 hr, alternately. Fraction sizes ranged from 1 to 12 Gy, and various numbers of fractions were given. At the end of fractionation, a top-up dose of 20 Gy was administered. The overall treatment time ranged from 2 to 21 days. The average skin reaction from 10 to 35 days after completion of irradiations was determined. The skin reactions started from 8 to 27 days following the completion of irradiations. The skin reaction after fraction sizes of 3.5 and 5 Gy was dependent on the total dose. The skin reaction after fraction sizes of 1.5 and 2 Gy showed a biphasic response; at lower total doses, the skin reaction was proportional to the total dose, but at higher total dose, the skin reaction reached a plateau. The average skin reaction at the plateau with fraction sizes of 1, 1.5, and 2 Gy were 0.79 +/- 0.03, 1.12 +/- 0.13, and 1.37 +/- 0.06, respectively. The alpha/beta ratio for acute skin reaction following the twice a day scheme was 9.09 Gy (at dose/fraction greater than or equal to 3.5 Gy). The plateau may be attributed to the effect of accelerated proliferation and a balance between cell depletion and proliferation during twice-a-day irradiations. It is also suggested that twice-a-day irradiations induce more proliferation in skin than once a day treatments.

The interactions of seven cancer chemotherapeutic drugs and radiation in normal skin were studied using the mouse foot skin scoring system. Single drug doses were administered 15 min before graded single doses of irradiation or at different intervals before and after a fixed radiation dose. Adriamycin (ADM), bleomycin (BLM), methotrexate (MTX), mitomycin-C (MM-C), and cis-platinum (cis-DDP) all significantly enhanced the radiation-induced skin reactions. The dose-effect factors (DEF) for these drugs ranged from 1.07 to 1.11. Cyclophosphamide (CTX) had a radioprotective effect (DEF 0.90), whereas 5-fluorouracil (5-FU) had no effect (DEF 1.00). The effect of ADM was present at administration from 6 h before to 2 min after irradiation, and the effect of BLM from 24 h before to 4 h after irradiation. The radioprotective effect of CTX and the enhanced effect of MM-C were only present on administration 15 min before and 2 min after irradiation. MTX and cis-DDP enhanced the skin reactions only when given before irradiation.

Effects of a range (2-50 Gy) of single doses of 250 kV X rays on epidermal Langerhans cells in vivo were quantified in groups of CBA/CaH mice. Animals were sacrificed and compared with controls on the 10th day after local irradiation of their hind feet, when Langerhans cell numbers were at a minimum. ATPase-positive Langerhans cells in sheets of footpad epidermis were counted by light microscopy and cells with Birbeck granules were enumerated by electron microscopy. Both methods revealed a dose-dependent loss of Langerhans cells after ionizing radiation. Fifty percent of the ATPase-positive cells were lost after 14.4 +/- 1.3 Gy, and 50% of Birbeck granule-containing cells were lost after 17.9 +/- 4.2 Gy, suggesting that differentiated epidermal Langerhans cells are radioresistant. Loss of equivalent proportions of ATPase-positive and ultrastructurally identifiable cells after a range of doses indicates that X rays do not merely alter Langerhans cell surface markers but actually deplete the epidermal population of these cells.

The effect of hyperthermia on radiation carcinogenesis was investigated in the C3Hf/Sed mouse foot. The foot was irradiated under hypoxic conditions, in air, or under hyperbaric oxygen conditions to evaluate the oxygen effect. Hyperthermia at 43.5 degrees C for 45 min was given by immersing the animal foot into a constant temperature water bath. A malignant tumor in the irradiated foot was first observed congruent to 250 days after irradiation. Tumors developed in the irradiated area until day 850. RCD50, or 50% radiation carcinogenesis dose was the endpoint and was calculated based on the tumor incidence 650 days after irradiation. RCD50 following radiation given alone under hypoxic conditions was 66.3 (60.0-73.2) Gy, and the oxygen enhancement ratio (hypoxic/hyperbaric oxygen) was 3.0 (2.5-3.5). Radiation carcinogenesis was enhanced by hyperthermia given with a 20 min treatment interval with no significant alteration in the oxygen effect. Thermal enhancement was greatest when hyperthermia was given 20 min prior to irradiation (2.5 [2.2-2.9] under hypoxia). No thermal enhancement was observed when two treatments were given with a treatment interval of 2 days. The median time to develop a malignant tumor decreased with increasing radiation dose. This median time was shorter following combined hyperthermia and irradiation (423 days) than following radiation alone (504 days). Histological studies revealed that more than 80% of tumors were soft tissue sarcomas, and the most common tumor was fibrosarcoma. Squamous cell carcinoma was found in 7% of all tumors.

A study is made of the relationship between early and late damage after irradiation of the feet or ears of rats. In one type of experiment in which large groups of animals were given the same dose, there was a good correlation between the early and late forms of damage. In another experiment, the relationship between these two forms of radiation damage was found to be unaltered by a single dose of X-rays given 8 months earlier. Thus, both types of experiment point to the early and late forms of reaction in the skin of rodents resulting from a common cause. Other relevant experimental data and their relationship to clinical observations are discussed.

The results of radiation treatment as visible residual damage are reported for acute skin reaction and foot deformity in mice exposed to argon ions. Two groups of 40 mice each were exposed to argon ions at the plateau and peak center of a 10-cm-wide Bragg peak to a fixed dose of 1200 and 1300 rad, respectively. A third group of 40 mice was exposed to 1750 rad of 250-kVp X rays while the fourth group was kept as controls. The acute skin reactions were scored for 60 days and foot deformity at 8 months after exposure. These mice were reexposed 8 months after the first exposure to graded doses of X rays ranging from 1200 to 2500 rad. Acute skin reactions were scored again for 60 days and foot deformity 8 months after the second exposure to graded doses of X rays. The results showed that no significant visible residual damage of the first treatment of either argon ions or X rays was observed after a second irradiation with X rays for acute skin reaction. For the end point deformity, however, residual damage of the first treatment was observed. The residual damage for foot deformity for argon ions does not seem to be higher than for X rays when the doses of first treatment with argon ions and X rays were matched to produce nearly uniform effect. The results also suggest a threshold dose to show the residual damage of the first treatment.

For the early mouse foot skin reactions an increase in RBE relative to 60Co has been found for the irradiations with X ray beams generated between 100 and 250 kVp at both the surface and depth, respectively. In most cases, the RBE of the late skin reactions for irradiations at the surface and at depth are significantly lower than those for the early reactions. The clinical implications of these results, the effect of a possible hypoxic fraction of cells in the skin, and the choice of a "standard" radiation modality for radiobiological experiments are discussed.

Mice receiving a first treatment with graded doses of various heavy charged particles (protons and heavy ions) to one of their hind legs were re-exposed to a fixed dose of x rays eight months later to study the "memory" of residual damage from the first treatment. No significant memory of the first radiation exposure was observed for acute skin rection. However, there is an indication of memory for foot deformity. The results do not seem to indicate any significant differences in memory after exposure to 60Co gamma rays compared with protons or heavy ions, if biological effectiveness of the doses is taken into consideration.

The temporary immunological depression previously demonstrated after high level head irradiation of adult rabbits seems to be due to decrease in lymphoblastic transformation capacity connected with encephalon injury.

The effects of fractionated irradiation on the feet of rats were the subjects of a time-dose study. The doses required to produce various levels of early skin damage, late skin damage, and late structural damage were determined for single doses and for treatments employing three fractions per week and lasting up to 50 days. The data did not follow the relationship first proposed by strandqvist, in which dose is proportional to time-n; rather, when the normal-tissue reactions were plotted on a linear-coordinate graph, they formed parallel time-dose isoeffect curves with distinct positive curvatures.

The effect of Corynebacterium parvum treatment on the response of tumor and normal tissue to hyperthermia (43.5 degrees) was studied. Animals were C3Hf/Sed mice from our defined flora mouse colony. The time at hyperthermia that achieved control of one-half of methylcholanthrene-induced fibrosarcomas and the foot reaction were examined after treatment. C. parvum, if given 3 to 32 days before hyperthermia, enhanced the reaction to local hyperthermia of normal tissue. No enhancement was observed if C. parvum was given after hyperthermia. This enhancement was more dramatic for tumor response resulting in a therapeutic gain factor of congruent to 2.3 (3.7/1.6). Comparative studies on combined Corynebacterium and radiation failed to demonstrate the enhancement to normal tissue.