Citations

Headaches are quite common in children and adolescents, and they appear to persist into adulthood in a sizable number of individuals. Assessment approaches (interview, pain diaries, and general and specific questionnaires) and behavioral treatment interventions (contingency management, relaxation, biofeedback, and cognitive behavior therapy) are reviewed, as is the evidence base for their use. The article concludes with practical suggestions for headache management.

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.

Abstract Purpose: Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent that induces apoptosis in multiple tumor cell types while sparing most normal cells. We determined the effect of ectopic Bcl-2 expression on TRAIL-induced apoptosis and whether the small molecule Bcl-2 inhibitor, HA14-1, could increase TRAIL sensitivity. Experimental Design: SW480 human colon cancer cells were stably transfected with the PC3-Bcl-2 plasmid or vector alone. Cells were incubated with recombinant human TRAIL ± HA14-1 or caspase-9 inhibitor (Z-LEHD-FMK). Apoptosis was analyzed by Annexin V-fluorescein isothiocyanate labeling and DNA fragmentation factor 45 (DFF45) cleavage. Clonigenic survival was also studied. Caspase activation was determined by immunoblotting or colorimetric assay. The cytosolic expression of Bid, Bax, and XIAP and release of cytochrome c and Smac/DIABLO were determined by immunoblotting. Results: Bcl-2 overexpression partially protected SW480 cells from a dose-dependent induction of apoptosis by TRAIL, as did a caspase-9 inhibitor, and increased their clonogenic survival. Bcl-2 overexpression attenuated TRAIL-induced cleavage of caspase-8, indicating its activation upstream and downstream of mitochondria, as well as cleavage of Bid and caspase-3. Bcl-2 inhibited TRAIL-induced Bax translocation, cytosolic release of cytochrome c and Smac/DIABLO, and the downstream cleavage of XIAP and DFF45. Coadministration of HA14-1 and TRAIL increased apoptosis in SW480/Bcl-2 cells by restoring Bax redistribution and cytochrome c release. Conclusions: Bcl-2 confers apoptosis resistance to TRAIL by inhibiting a mitochondrial amplification step and by inactivating downstream XIAP in SW480 cells. HA14-1 reversed Bcl-2–mediated TRAIL resistance, suggesting a novel strategy for increasing TRAIL sensitivity in Bcl-2–overexpressing colon cancers.