Citations

Many therapeutic procedures have been introduced into the art and science of medical practice empirically by a method of trial and error. Such a method has marked limitations and may produce unfavorable consequences. The facilities available in experimental medicine permit a thorough and extensive investigation of biological effects of many therapeutic agents or procedures before any clinical application is made. Optimal doses of the therapeutic agent can be approximated and a comparative study of various technics designed for clinical application can be made. Unfortunately ultrasound was used clinically by certain enthusiastic therapeutists before a thorough study of its biologic effects was completed. These therapeutists regarded the major biologic effect of ultrasonic energy to be mechanical. They were aware of a heating effect, but considered that it played a minor role. Experimental measurements have shown clearly that the major effect of ultrasound on living tissues is thermal when an intensity suitable for therapy is employed. The heating of bone by ultrasound is spectacular. No other heating agent used in therapy can raise the temperature of bone to such high levels so quickly. The application of ultrasound for diagnostic purposes and also for instrumentation will be described.

Experimental investigations indicate that ultrasound may prove useful for therapy, for diagnosis, and for biologic measurement. Ultrasound, although it may be dangerous in unskilled hands, is an excellent agent for the structural heating of living tissues. The term “structural heating” is used to denote heating at abrupt interfaces.The living organism presents numerous abrupt interfaces. Ultrasound promises to become a reliable diagnostic tool. Either the transmitted or the reflected ultrasonic energy can be used in this application. Tumors, gallstones, kidney stones, stones in the salivary glands, foreign bodies, and abnormal collections of fluid have been located accurately. Preliminary observations on the use of ultrasound for certain biologic measurements are encouraging. Instrumentation for biologic measurement includes ultrasonic flowmeters, devices for measuring thickness of some tissue structures, and equipment for measuring the viscosity of blood.

Experiments have been carried out to investigate ultrasound as a possible therapeutic agent. These show that selective heating occurs in nerves and bones treated in situ. Effects of direct heat on nerves are strikingly similar to the effects of ultrasound. Blocking of nerves by sound or heat with present techniques seems impractical because the margin of safety is too narrow.

As early as 1932 Freundlich, Sollner, and Rogowski proposed the use of ultrasonics in medicine for diathermy. They were able to demonstrate that bone marrow could be heated. The results of their study indicated clearly that further experiments needed to be done to extend these preliminary observations. We have completed a study of the temperatures produced by ultrasonics in bone marrow, bone, and adjacent tissues in the extremities of the dog. The frequency used in these studies was 800 kilocycles per second. The maximum output of the ultrasonic generator was approximately 15 watts. High temperatures can be produced in bone marrow and bone with relatively low outputs of ultrasonic energy. The adjacent tissues are heated only moderately. Ultrasonics must be used with caution in the proximity of bones because the temperatures produced in bone and bone marrow may rise to dangerous levels within a very few minutes.

Dilute suspensions of canine erythrocytes were exposed to 1 Mc focused ultrasonic fields with maximum acoustic pressures estimated at 10 atm. In standing wave patterns in which circulation was inhibited, the cells clumped rapidly at the nodes and no changes were found. With a free surface, fountaining and stirring occurred. Exposure at 1 atm ambient pressure then resulted in rapid lysis. Erythrocytes exposed briefly in isotonic Rous-Turner mixture and controls were both diluted with sodium chloride solutions of varying concentration. The optical density at 650 mμ was plotted as a function of salt concentration. The exposed samples showed a greater fractional decrease in optical density at low sodium chloride concentrations than did the controls. Other samples exposed in hypotonic solutions showed both the greater sensitivity to low sodium chloride concentrations and a smaller change in optical density as the sodium chloride was varied from isotonic to 70% isotonic. It has not been possible to demonstrate that any factor other than cavitation was responsible for the observed changes in osmotic fragility.

By use of a high-power, corona type loudspeaker we have been able to demonstrate behavioral and endocrine responses of laboratory rodents to measured high sound-pressure levels at the frequencies at which their hearing is most sensitive, namely, 10 to 40 kc. The corona type loudspeaker behaves in the fashion predicted by the theoretical analysis reviewed in this paper. It is limited by extremely low efficiency (2.5%) and high production of ozone. At high frequencies it is limited by the volume of the corona, and at low frequencies by the failure of the quasi-adiabatic condition within the corona. Despite these limitations its performance has not been equaled by other types of loudspeakers; it is a unique tool for studying the responses of laboratory rodents to sound fields.

AbstractGenetic counseling students were surveyed about their backgrounds, application process to genetic counseling programs, and career motivations and plans. Program directors from 27 accredited programs were asked to distribute 362 surveys to students. Fifty‐two survey items assess demographics; sources of support for pursuing a genetic counseling career (information about genetic counseling, encouragement/discouragement from others); career motivations (reasons for applying and for becoming a genetic counselor); and career certainty. Two hundred and thirty‐five usable surveys were returned (64.9% usable return rate). Most respondents were Caucasian females (mean age = 25.4 years). About 13% identified as ethnic minorities, and about one‐third reported family histories of a genetic condition(s). Most respondents learned about the field in classes, and most were strongly encouraged by family and friends to pursue genetic counseling. Reasons rated as most important for becoming a genetic counselor included helping others and intellectual stimulation. Recruitment, training, and research recommendations are given.

Abstract We demonstrated that B-cell–dendritic cell (DC) interactions via transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI) and B-lymphocyte stimulator (BLyS) provide an early signal critical to generate adequate numbers of mature antigen presenting cells (APCs) to prime naive CD8+ T cells (CTLs) in vivo. Evidence that B cells are required for efficient CTL generation in mice and that reconstitution with wild-type but not TACI-knockout B cells restored normal CTL responses support our conclusion. Moreover, low doses of a TACI fusion protein (TACI-Fc) that express the extracellular domain of TACI (amino acid [aa] 1-126) restored CTL priming in B-cell–deficient mice in vivo and induced DC maturation in vitro. In fact, following interactions with B cells, splenic DCs rapidly express the CD86 costimulatory molecule, to an extent comparable to the exposure to antigenic stimuli. BLyShigh peptide-pulsed bone marrow–derived DCs, used as vaccines in vivo, cannot generate CTLs in B-cell–deficient and TACI-deficient mice, strongly supporting a need for B-cell–DC cooperation through TACI-BLyS during CTL first encounter with antigens in vivo.

Purpose Most patients with colorectal liver metastases present to general surgeons and oncologists without a specialist interest in their management. Since treatment strategy is frequently dependent on the response to earlier treatments, our aim was to create a therapeutic decision model identifying appropriate procedure sequences. Methods We used the RAND Corporation/University of California, Los Angeles Appropriateness Method (RAM) assessing strategies of resection, local ablation and chemotherapy. After a comprehensive literature review, an expert panel rated appropriateness of each treatment option for a total of 1,872 ratings decisions in 252 cases. A decision model was constructed, consensus measured and results validated using 48 virtual cases, and 34 real cases with known outcomes. Results Consensus was achieved with overall agreement rates of 93.4 to 99.1%. Absolute resection contraindications included unresectable extrahepatic disease, more than 70% liver involvement, liver failure, and being surgically unfit. Factors not influencing treatment strategy were age, primary tumor stage, timing of metastases detection, past blood transfusion, liver resection type, pre-resection carcinoembryonic antigen (CEA), and previous hepatectomy. Immediate resection was appropriate with adequate radiologically-defined resection margins and no portal adenopathy; other factors included presence of ≤ 4 or > 4 metastases and unilobar or bilobar involvement. Resection was appropriate postchemotherapy, independent of tumor response in the case of ≤ 4 metastases and unilobar liver involvement. Resection was appropriate only for > 4 metastases or bilobar liver involvement, after tumor shrinkage with chemotherapy. When possible, resection was preferred to local ablation. Conclusion The results were incorporated into a decision matrix, creating a computer program (OncoSurge). This model identifies individual patient resectability, recommending optimal treatment strategies. It may also be used for medical education.