Arrhenius thermodynamics and birth defects: chemical teratogen synergy. Untested, testable, and projected relevance.

This article addresses the issue of hyperthermia-induced birth defects with an accompanying additional teratogen, be it a chemical or a physical agent (i.e., a simultaneous "combinational" exposure to two teratogens, one of which is hyperthermia).

Fetal thermal dose considerations during the obstetrician's watch: Implications for the pediatrician's observations.

There are a number of seemingly "usual" thermal episodes during pregnancy for which it is relatively easy to determine a rudimentary aspect of thermal dose; these episodes include fever, labor, labor plus epidural, and the normally-occurring 0.5 degrees C temperature elevation above maternal core temperature of the fetus during the entirety of the third trimester. Complications can involve, for instance, fever during the third trimester.

Quantification of risk from fetal exposure to diagnostic ultrasound.

Biomedical ultrasound may induce adverse effects in patients by either thermal or non-thermal means. Temperatures above normal can adversely affect biological systems, but effects also may be produced without significant heating. Thermally induced teratogenesis has been demonstrated in many animal species as well as in a few controlled studies in humans.

Biological and environmental factors affecting ultrasound-induced hemolysis in vitro: 5. Temperature.

This research project tested the hypothesis that cold-equilibrated (approximately 0 degrees C) human erythrocytes in vitro in the presence of an ultrasound contrast agent (Albunex) will undergo greater ultrasound-induced hemolysis than physiologically equilibrated (37 degrees C) human erythrocytes in vitro because of a temperature-related transition in membrane fluidity leading to increased fragility. First, it was shown that cold-equilibrated erythrocytes are more susceptible to mechanically induced hemolysis than physiologically equilibrated erythrocytes. Second, when adjustments were made for (1) temperature-dependent efficiencies of a 1-MHz transducer (200 micros pulse length, 20 ms interpulse interval, 30 s exposure duration) such that when cold or physiological temperatures were employed, there were equivalent acoustic outputs in terms of peak negative pressure (MPa P-) and (2) comparable viscosities of the 0 and 37 degrees C blood plasmas, the cold (approximately 0 degrees C) erythrocytes displayed substantially greater amounts of ultrasound-induced hemolysis than the physiological (37 degrees C) erythrocytes.

Cell size relations for sonolysis.

The occurrence of cell lysis following exposure to ultrasound (US) has been well documented; the specifics of the mechanistic process(es) involved have proven to be difficult to characterize. There appear to be two major mechanisms of US-induced cell lysis in vitro, acoustic cavitation and bubble transport. Both involve shear forces.

An extended commentary on "Models and regulatory considerations for transient temperature rise during diagnostic ultrasound pulses" by Herman and Harris (2002).

This commentary addresses the matter of misinterpretation of thermal dose as discussed by Herman and Harris (2002), and shows that the thermal doses they would consider as ineffective (i.e., "safe") for producing a hyperthermia-induced teratologic effect, can be highly effective ones.

The relevance of cell size on ultrasound-induced hemolysis in mouse and human blood in vitro.

This paper describes a further test of the hypothesis that cell size is an important physical parameter in ultrasound (US)-induced hemolysis, that is, the larger the cell the greater the potential for sonolysis by a cavitational mechanism. Mouse (M) and human (Hu) erythrocytes in vitro were used; their mean corpuscular volumes were 49.0 and 89.

Comparative hemolytic effectiveness of 1 MHz ultrasound on human and rabbit blood in vitro.

This project continued testing of the general working hypothesis that cell size is a physical determinant in extent of ultrasound (US)-induced hemolysis, the larger the cell the greater the lysis. For this project, the specific hypothesis tested was that human erythrocytes, being larger than rabbit erythrocytes, would be the more sensitive to sonolysis induced by inertial cavitation in the presence of Albunex, a US contrast agent. The rationale behind this hypothesis was 1.

The pulse length-dependence of inertial cavitation dose and hemolysis.

Gas-based ultrasound (US) contrast agents increase erythrocyte sonolysis, presumably via enhancing inertial cavitation (IC) activity. The amount of IC activity (IC "dose") and hemolysis generated by exposure to 1.15 MHz US were examined with different US pulse lengths, but with the same delivered acoustic energy, for Optison and Albunex.

Biological and environmental factors affecting ultrasound-induced hemolysis in vitro: medium tonicity.

Whole human anticoagulated blood in vitro underwent controlled plasma replacement with either isotonic (0.9%) or hypotonic (0.5%) saline to 1.

Biological and environmental factors affecting ultrasound-induced hemolysis in vitro: 3. Antioxidant (Trolox) inclusion.

This project tested the hypothesis that human erythrocytes pretreated with Trolox (a water-soluble analog of vitamin E) would be more susceptible to ultrasound (US)-induced hemolysis by a cavitational mechanism because of an increased fragility of the erythrocyte membrane over that without Trolox supplementation. Samples of whole human blood from apparently healthy donors (hematocrit approximately 40%) in vitro were supplemented or not supplemented with Trolox at various concentrations, ranging from 1.8 to 0.

Biological and environmental factors affecting ultrasound-induced hemolysis in vitro: 2. Medium dissolved gas (pO2) content.

The data collected in this project supported the a priori hypothesis that the concentration of dissolved oxygen in whole human blood in vitro affected the extent of ultrasound (US)-induced hemolysis under conditions conducive to the occurrence of inertial cavitation. Aliquots of whole human blood in vitro with a relatively high O(2) level had statistically significantly more 1-MHz US-induced hemolysis than aliquots with a relatively low O(2) level in the presence of controlled gas nucleation (Albunex or ALX, supplementation), with US-induced hemolytic yields being substantially less at 2.2- and 3.

Biological and environmental factors affecting ultrasound-induced hemolysis in vitro: 1. HIV macrocytosis (cell size).

This paper reports the results of a further test of the hypothesis that the extent of ultrasound (US)-induced cell lysis in the presence of a US contrast agent to enhance cavitational effects is a function of cell size. The present data support the hypothesis. Human adult erythrocytes in vitro derived from patients with HIV (n = 15) and apparently healthy individuals (n = 15) were compared for US-induced hemolysis in vitro.

Biological Effects of Ultrasound. The Perceived Safety of Diagnostic Ultrasound Within the Context of Ultrasound Biophysics: A Personal Perspective.

This brief review addresses the issue of health and safety from exposure to diagnostic ultrasound. The exemplary historical record of diagnostic ultrasound exposures is coupled with great patient benefit. However, the power outputs of clinical devices have been increasing over the past decade such that inertial cavitation seems reasonably likely to occur if appropriate gas nuclei are present.

Temporality in Ultrasound-Induced Cell Lysis In Vitro.

To test the hypothesis that the full extent of in vitro cell lysis due to ultrasound becomes evident with time lapse following insonation, human erythrocytes (2% hematocrit) in autologous plasma were mixed with Albunex(R), a pulse echo contrast agent, and exposed to 1-MHz, continuous-wave ultrasound (US) (5 W/cm(2) SPTA intensity) for 60 seconds while in a rotating (200 rpm) dialysis membrane vessel. Exposed and sham-exposed samples were subsequently assayed for hemolysis colorimetrically, either immediately or after a delay of 3 hours. Hemolysis was dependent on the interval between US exposure and assay, with significantly greater lysis evident with delayed assay.