Thermal thresholds for teratogenicity, reproduction, and development.
ABSTRACT The human embryo and foetus may be especially vulnerable to chemical and physical insults during defined stages of development. In particular, the scheduled processes of cell proliferation, cell migration, cell differentiation, and apoptosis that occur at different times for different organ structures can be susceptible to elevated temperatures. With limited ability to regulate temperature on its own, the developing embryo and foetus is entirely dependent upon the mother's thermoregulatory capacity. As a general rule, maternal core body temperature increases of ∼2°C above normal for extended periods of time, 2-2.5°C above normal for 0.5-1 h, or ≥4°C above normal for 15 min have resulted in developmental abnormalities in animal models. Significant differences in thermoregulation and thermoneutral ambient temperatures make direct extrapolation of animal data to humans challenging, and the above temperatures may or may not be reasonable threshold predictions for adverse developmental effects in humans. Corresponding specific absorption rate (SAR) values that would be necessary to cause such temperature elevations in a healthy adult female would be in the range of ≥15 W/kg (whole body average or WBA), with ∼4 W/kg required to increase core temperature 1°C. However, smaller levels of thermal stress in the mother that are asymptomatic might theoretically result in increased shunting of blood volume to the periphery as a heat dissipation mechanism. This could conceivably result in altered placental and umbilical blood perfusion and reduce heat exchange with the foetus. It is difficult to predict the magnitude and threshold for such an effect, as many factors are involved in the thermoregulatory response. However, a very conservative estimate of 1.5 W/kg WBA (1/10th the threshold to protect against measurable temperature increases) would seem sufficient to protect against any significant reduction in blood flow to the embryo or foetus in the pregnant mother. This is more than three times above the current WBA limit for occupational exposure (0.4 W/kg) as outlined in both IEEE C95.1-2005 and ICNIRP-1998 international safety standards for radiofrequency (RF) exposures. With regard to local RF exposure directly to the embryo or foetus, significant absorption by the mother as well as heat dissipation due to conductive and convective exchange would offer significant protection. However, a theoretical 1-W/kg exposure averaged over the entire 28-day embryo, or averaged over a 1-g volume in the foetus, should not elevate temperature more than 0.2°C. Because of safety standards, exposures to the foetus this great would not be attainable with the usual RF sources. Foetal exposures to ultrasound are limited by the US Food and Drug Administration (FDA) to a maximum spatial peak temporal average intensity of 720 mW/cm(2). Routine ultrasound scanning typically occurs at lower values and temperature elevations are negligible. However, some higher power Doppler ultrasound devices under some conditions are capable of raising foetal temperature several degrees and their use in examinations of the foetus should be minimised.
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ABSTRACT: This article is the presentation I gave at the D'Arsonval Award Ceremony on June 14, 2011 at the Bioelectromagnetics Society Annual Meeting in Halifax, Nova Scotia. It summarizes my research activities in acoustic and electromagnetic millimeter waves over the past 47 years. My earliest research involved acoustic millimeter waves, with a special interest in diagnostic ultrasound imaging and its safety. For the last 21 years my research expanded to include electromagnetic millimeter waves, with a special interest in the mechanisms underlying millimeter wave therapy. Millimeter wave therapy has been widely used in the former Soviet Union with great reported success for many diseases, but is virtually unknown to Western physicians. I and the very capable members of my laboratory were able to demonstrate that the local exposure of skin to low intensity millimeter waves caused the release of endogenous opioids, and the transport of these agents by blood flow to all parts of the body resulted in pain relief and other beneficial effects. Bioelectromagnetics. © 2012 Wiley Periodicals, Inc.Bioelectromagnetics 08/2012; · 2.02 Impact Factor
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ABSTRACT: Purpose: This study aims to evaluate the effects of fever on follicular development in women undergoing controlled ovarian stimulation during in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) cycles. Materials and methods: This was a retrospective observational self-controlled study at a tertiary-care fertility centre. Six gonadotropin stimulation cycles characterised by poor ovarian response in which women reported the occurrence of a febrile illness, were considered for evaluation. Fever-exposed cycles were compared to the next stimulation cycle in the same women. Primary outcome measures were final number of pre-ovulatory follicles (≥ 16 mm) and final peak serum estradiol levels (pg/mL). Other outcome measures were final number of medium-sized follicles (12-15 mm), final mean estradiol serum level per follicle ≥ 12 mm (pg/mL), total days of stimulation and total gonadotropin ampoules utilised. Results: Fever-exposed cycles were associated with significantly lower number of pre-ovulatory follicles (0.7 ± 0.8), significantly higher number of medium-size follicles (21.0 ± 4.5), and significantly reduced serum estradiol per follicle ≥12 mm (50.7 ± 11.7 pg/mL). They also required a significantly longer duration of ovarian stimulation (15.7 ± 3.3 days) and a significantly increased number of gonadotropin ampoules (47.2 ± 10.9). Four women had polycystic ovary syndrome and one hypothalamic hypogonadism. Conclusion: This preliminary report suggests a possible negative effect of fever on follicular development and ovarian estradiol production in some women undergoing controlled ovarian stimulation.International Journal of Hyperthermia 10/2012; · 2.59 Impact Factor
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ABSTRACT: OBJECTIVE: To define thresholds of safe local temperature increases for MR equipment that exposes patients to radiofrequency fields of high intensities for long duration. These MR systems induce heterogeneous energy absorption patterns inside the body and can create localised hotspots with a risk of overheating. METHODS: The MRI + EUREKA research consortium organised a "Thermal Workshop on RF Hotspots". The available literature on thresholds for thermal damage and the validity of the thermal dose (TD) model were discussed. RESULTS/CONCLUSIONS: The following global TD threshold guidelines for safe use of MR are proposed: 1. All persons: maximum local temperature of any tissue limited to 39 °C 2. Persons with compromised thermoregulation AND (a) Uncontrolled conditions: maximum local temperature limited to 39 °C (b) Controlled conditions: TD < 2 CEM43°C 3. Persons with uncompromised thermoregulation AND (a) Uncontrolled conditions: TD < 2 CEM43°C (b) Controlled conditions: TD < 9 CEM43°C The following definitions are applied: Controlled conditions A medical doctor or a dedicated trained person can respond instantly to heat-induced physiological stress Compromised thermoregulation All persons with impaired systemic or reduced local thermoregulation KEY POINTS : • Standard MRI can cause local heating by radiofrequency absorption. • Monitoring thermal dose (in units of CEM43°C) can control risk during MRI. • 9 CEM43°C seems an acceptable thermal dose threshold for most patients. • For skin, muscle, fat and bone,16 CEM43°C is likely acceptable.European Radiology 04/2013; · 3.55 Impact Factor