Case Report: Industrial X-Ray Injury Treated With Non-Cultured Autologous Adipose-Derived Stromal Vascular Fraction (SVF).

Local cutaneous injuries induced by ionizing radiation (IR) are difficult to treat. Many have reported local injection of adipose-derived stromal vascular fraction (SVF), often with additional therapies, as an effective treatment of IR-induced injury even after other local therapies have failed. The authors report a case of a locally recurrent, IR-induced wound that was treated with autologous, non-cultured SVF without other concurrent therapy. A nondestructive testing technician was exposed to 130 kVp x rays to his non-dominant right thumb on 5 October 2011. The wound healed 4 mo after initial conservative therapy with oral/topical α-tocopherol, oral pentoxifylline, naproxen sodium, low-dose oral steroids, topical steroids, hyperbaric oxygen therapy (HBOT), oral antihistamines, and topical aloe vera. Remission lasted approximately 17 mo with one minor relapse in July 2012 after minimal trauma and subsequent healing. Aggressive wound breakdown during June 2013 required additional therapy with HBOT. An erythematous, annular papule developed over the following 12 mo (during which time the patient was not undergoing prescribed treatment). Electron paramagnetic resonance (EPR) done more than 2 mo after exposure to IR revealed dose estimates of 14 ± 3 Gy and 19 ± 6 Gy from two centers using different EPR techniques. The patient underwent debridement of the 0.5 cm papular area, followed by SVF injection into and around the wound bed and throughout the thumb without complication. Eleven months post SVF injection, the patient has been essentially asymptomatic with an intact integument. These results raise the possibility of prolonged benefit from SVF therapy without the use of cytokines. Since there is currently no consensus on the use of isolated SVF therapy in chronic, local IR-induced injury, assessment of this approach in an appropriately powered, controlled trial in experimental animals with local radiation injury appears to be indicated.

A three-hour measurement to evaluate bone calcium turnover.

It is well established that short-term clearance of an intravenous calcium load in vivo reflects bone uptake. Using results from isotope-dilution experiments with 42Ca, a 3-h test has been developed to measure a quantity, gamma, related to bone accretion. This test is proposed as a useful, clinically applicable measure of bone status. For early times, t, after a bolus of 42Ca, plasma tracer dilution was well approximated by t-gamma, where gamma is related to the fractional rate of loss of tracer, q, from blood into bone (1/q)(dq/dt) = -gamma/t). Gamma was evaluated from kinetic measurements on 91 normal female children, adolescents, and adult women in the age range 4-50 years. For t < or = 3 h, all clearance curves were well fit by a power function. Gamma was found to vary from 0.244 +/- 0.031 for adult premenopausal women (N = 22) to 0.392 +/- 0.056 for prepubertal children (N = 29). Using the Spearman rank-order correlation test, gamma was correlated with bone accretion measured from classic calcium kinetic studies with a correlation coefficient of 0.721, significant at p < 0.005. In those cases in which accretion and resorption remain tightly linked, gamma also provides information on the state of calcium loss from bone. Gamma was evaluated in 14 subjects with bone disease characterised by increased resorption (osteoporosis, Paget's disease) and in 27 subjects with decreased accretion (osteogenesis imperfecta, types I, III, IV; steroid-treated juvenile dermatomyositis). All subjects with Paget's disease and with osteoporosis showed increased gamma, consistent with high bone turnover. The osteoporotic patients furthermore exhibited gamma increasing monotonically by approximately 1% per year after age 55.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrasonic pulse-echo determination of thermal injury in deep dermal burns.

Burns of all kinds represent a serious class of traumatic injury, affecting over two million people annually in the United States alone. Of this number, over 70000 are serious enough to require extended hospitalization. Currently, there is no sensitive, quantitative technique for measuring the depth of thermal damage in such injuries. An ultrasonic pulse-echo technique is described here whereby such information can be obtained within a few minutes postburn. Results from model porcine experiments are given to illustrate the usefullness of the method, and implication for the clinical care of human burn victims are discussed.

Early dose assessment following severe radiation accidents.

Early treatment of victims of high level acute whole-body x-ray or gamma exposure has been shown to improve their likelihood of survival. However, in such cases, both the magnitude of the exposure and the dosimetry profile(s) of the victim(s) are often not known in detail for days to weeks. A simple dose-prediction algorithm based on lymphocyte kinetics as documented in prior radiation accidents is presented here. This algorithm provides an estimate of dose within the first 8 h following an acute whole-body exposure. Early lymphocyte depletion kinetics after a severe radiation accident follow a single exponential, L(t) = L(o)e(-k(D¿t), where k(D) is a rate constant, dependent primarily on the average dose, D. Within the first 8 h post-accident, K(D) may be calculated utilizing serial lymphocyte counts. Data from the REAC/TS Radiation Accident Registry were used to develop a dose-prediction algorithm from 43 gamma exposure cases where both lymphocyte kinetics and dose reconstruction were felt to be reasonably reliable. The inverse relationship D(K) may be modeled by a simple two parameter curve of the form D = a/(1 + b/K) in the range 0 < or = D < or = 15 Gy, with fitting parameters (mean +/- SD): a = 13.6 +/- 1.7 Gy, and b = 1.0 +/- 0.20 d(-1). Dose estimated in this manner is intended to serve only as a first approximation to guide initial medical management.

Early dose assessment in criticality accidents.

Early estimation of dose is useful in the medical evaluation of severe radiation accidents. In a prior publication, lymphocyte depletion kinetics were shown to follow an exponential decline for gamma accidents in which the average whole-body dose was in the range 50 cGy < D < 8-10 Gy. In that study, the depletion rate constant was linearly related to dose, within the statistical variation of the historical hematological data. This simple technique has now been extended to include analysis of various types of criticality accidents (liquid process; water moderated systems; metallic systems). Lymphocyte depletion in high-level mixed gamma/neutron accidents is found to be approximately equal, at a given effective dose, to that for gamma accidents. This universality would indicate a neutron RBE for human lymphocytes close to unity. Furthermore, the technique appears to be insensitive to the shape of gamma and neutron spectra, therefore making it especially robust for initial, approximate dose estimation.

Biodosimety Assessment Tool: a post-exposure software application for management of radiation accidents.

The Biodosimetry Assessment Tool software application under development will equip health care providers with diagnostic information (clinical signs and symptoms, physical dosimetry, etc.) germane to the management of human radiation casualties. Designed primarily for prompt use after a radiation incident, the user-friendly program facilitates collection, integration, and archiving of data obtained from exposed persons. Data collected in templates are compared with established radiation dose responses obtained from the literature to provide multiparameter dose assessments. The program archives clinical information (e.g., extent of contamination, wounds, infection, etc.) useful for casualty management, displays relevant diagnostic information in a concise format, and can be used to manage both military and civilian radiation accidents. In addition, monitoring of diagnostic information of individuals using this program could potentially minimize the severity of psychological casualties by making a marked impact on the way that both radiation casualties and the worried well view their exposure, dose, and future risk for the development of disease.

Use of stable isotopic tracers in studies of whole body calcium metabolism.

Stable isotopic tracers of calcium have been used to characterize the absorption of dietary calcium and the subsequent distribution of this element through the body. For a group of 7 healthy children, ages 4-14, and 7 children with osteogenesis imperfecta (OI), types I, III and IV, ages 6-17, there were no detectable differences in the fractional absorption of dietary calcium, 0.29+/-0.11 and 0.28+/-0.16, respectively. The total exchangeable pool of calcium was found to be 161+/-52 mg/kg for the healthy children and 95+/-29 mg/kg for the 3 children with Type I OI, 250+/-75 mg/kg for the 3 children with Type III OI and 216 mg/kg for the child with Type IV OI.

A non-Markovian model for calcium kinetics in the body.

We present a new generalized compartmental model for calcium kinetics as measured by tracer concentration in blood plasma. The parameter measuring incorporation of calcium in bone discriminates between different levels of physical development in female teenagers and between teenagers and adults.

Calcium kinetics in children with osteogenesis imperfecta type III and IV: pre- and post-growth hormone therapy.

Children with osteogenesis imperfecta (OI) type III and type IV were studied using a (42)Ca stable isotope technique. Serum dilution kinetics of (42)Ca were studied pre- and post-growth hormone (GH) treatment in 9 OI III (age range 5-9 years) and 8 OI IV patients (age range 5-12 years). Each subject was studied twice: at baseline and following GH therapy (range 1-1.5 years). Isotopic enrichments of (42)Ca were followed over 7 days using thermal ionization mass spectrometry. A binding site model, which describes reversible and irreversible binding of calcium (Ca) ions to postulated short- and long-term binding sites in bone, was used to analyze the kinetic data. In type III patients, GH treatment (1) increased the fraction of short-term binding sites, theta (0.777 +/- 0.112 versus 0.877 +/- 0.05, respectively; P = 0.034); (2) increased the apparent half-life of a Ca ion attached to the long-term binding site by 76% (P = 0. 009); (3) although not statistically significant (P = 0.098), a trend toward an increased growth rate was observed with increasing change in theta (Deltatheta); (4) patients experienced a 75% increase in growth rate during the first 6 months of treatment. In type IV patients, GH treatment increased the apparent half-life of a Ca ion attached to the long-term binding site by 83% (P = 0.048), however, no trend toward an increased growth rate was observed with increasing Deltatheta in these patients. These significant changes in Ca binding to bone may influence growth in type III patients.

Calcium kinetics in glycogen storage disease type 1a.

Glycogen storage disease type 1a (Von Gierke's disease) is one of the more common glycogen storage diseases (GSD). GSD 1a patients can have severe idiopathic osteopenia, often beginning at a young age. Since calcium tracer studies offer a sensitive probe of the bone microenvironment and of calcium deposition, kinetics might be disturbed in patients with GSD 1a. Plasma dilution kinetics obtained using the stable isotope 42Ca are shown in this paper to be quite different between GSD 1a patients and age-matched controls. Comparison of kinetic parameters in these two populations is made using a new binding site model for describing calcium dynamics at the plasma-bone interface. This model describes reversible binding of calcium ions to postulated short-term and long-term sites by a retention probability density function psi (t). Using this analysis, adult GSD subjects exhibited a significant decrease (P = 0.023) in the apparent half-life of a calcium ion on the longer-term site compared with controls. The general theory of calcium tracer dilution kinetics is then discussed in terms of a new model of short-term calcium homeostasis recently proposed by Bronner and Stein [5].

Calcium tracer kinetics show decreased irreversible flow to bone in glucocorticoid treated patients.

Osteopenia resulting from pharmacologic doses of glucocorticoids is well known. Previously, there has been no satisfactory quantitative model describing the kinetics of calcium flow in subjects on chronic steroid use. A mathematical model of calcium isotope interaction with bone is described and applied to determine an estimate of kinetic parameters characterizing these changes. Calcium tracer dilution kinetics after a bolus injection of 42Ca were measured in 14 subjects with juvenile dermatomyositis, 6 on prednisone regimens and 8 on treatment regimens without prednisone. Irreversible tracer loss from plasma bone is found to be significantly reduced (P = 0.043) in the glucocorticoid-treated patients compared with patients on nonsteroid regimens. Reversible flow to bone is noted to be similar in the two groups. These results suggest a direct effect of glucocorticoids on osteoblast function.