Ultrasound and microbubble-targeted delivery of therapeutic compounds: ICIN Report Project 49: Drug and gene delivery through ultrasound and microbubbles.

The molecular understanding of diseases has been accelerated in recent years, producing many new potential therapeutic targets. A noninvasive delivery system that can target specific anatomical sites would be a great boost for many therapies, particularly those based on manipulation of gene expression. The use of microbubbles controlled by ultrasound as a method for delivery of drugs or genes to specific tissues is promising. It has been shown by our group and others that ultrasound increases cell membrane permeability and enhances uptake of drugs and genes. One of the important mechanisms is that microbubbles act to focus ultrasound energy by lowering the threshold for ultrasound bioeffects. Therefore, clear understanding of the bioeffects and mechanisms underlying the membrane permeability in the presence of microbubbles and ultrasound is of paramount importance. (Neth Heart J 2009;17:82-6.).

Assessment of endoleak significance after endovascular repair of abdominal aortic aneurysms: a lumped parameter model.

The outcome of endovascular repair of abdominal aortic aneurysms (AAAs) is greatly compromised by the possible occurrence of endoleak. Previously, the causes and effects of endoleak on a patient-specific basis have mainly been investigated in experimental studies. In order to both reconcile and physically substantiate the various experimental findings, a lumped parameter model of an incompletely excluded AAA was developed. After experimental validation, the model was applied to study the effects on the intrasac pressure of the degree of endoleak, the degree of stent-graft compliance, and the resistance of a possible outflow tract formed by a branching vessel. It is concluded that the presence of endoleak leads to elevated intrasac pressure, the mean of which is mainly governed by the outflow tract resistance, while the pulse pressure is governed by both the endoleak resistance and the stent-graft compliance. Based on the agreement of the current results with previous findings, it is further concluded that the lumped parameter modelling method provides a useful numerical tool for validating experimental endoleak studies.

Central auditory processing disorders and reduced motivation: three case studies.

The central auditory test results for three normal-hearing children who were initially diagnosed as having a central auditory processing disorder and learning disability are presented. They were referred to the authors for second-opinion consultations. Central auditory processing retesting was performed by the authors under the condition of no reinforcement and then the condition of reinforcement with the child's favorite food, hobby, or toy. For all three cases, the central auditory test scores improved markedly bilaterally under the condition of reinforcement as compared with the condition of no reinforcement. We hypothesize that the improvement was related to increased motivation associated with the reinforcement and that these children represented false-positive results on the central auditory test battery. Large-sample studies are needed to investigate the effect of reinforcement on test performance in children with reduced central auditory test scores.

Asymmetric suprathreshold speech recognition and the telephone ear phenomenon.

We compared interaural suprathreshold speech recognition scores in 62 adults with sensorineural hearing loss. Subjects were tested at two sites, 25 at the Baylor College of Medicine, Houston, TX and 37 at Brooklyn College, Brooklyn, NY. Ears were categorized according to telephone usage. Results showed, at both sites, a small but significant difference in speech understanding scores between the ear habitually used on the telephone and the opposite, nontelephone ear. The average speech recognition score was approximately 5 percent better on the telephone ear. Results are interpreted in relation to the theories of auditory deprivation and auditory acclimatization.

Auditory deprivation and recovery in adults with asymmetric sensorineural hearing impairment.

The purpose of this investigation was to investigate (1) whether auditory deprivation effects are present in the poorer ears of adults with asymmetric sensorineural hearing impairment and (2) whether, if such effects are present, they can be reversed by amplification. Subjects were 16 males with asymmetric sensorineural hearing impairment, 8 of whom had never been aided, 6 of whom were aided monaurally at the initial test, and 2 of whom were unaided at the initial test but aided monaurally later on. Data were obtained from a retrospective review of records. The initial and retest (2-13 years post initial test) suprathreshold speech-recognition scores for 50-word, taped lists of the CID W-22 PB words were analyzed. The results revealed a significant difference between the initial and retest mean suprathreshold speech-recognition scores for the poorer ears of the unaided subjects. The results also revealed no significant change from the initial test to retest in six of the aided ears and significant improvement from the initial test to retest in the two of the aided ears. The findings are discussed with reference to the theory of auditory deprivation and recovery from auditory deprivation by amplification.

Effects of prolonged lack of amplification on speech-recognition performance: preliminary findings.

The purposes of this investigation were two-fold: 1) to prospectively investigate the effect of prolonged lack of binaural amplification in the unaided ears of adults with bilaterally symmetrical sensorineural hearing impairment (BSSHI) fitted monaurally; and, 2) to prospectively investigate the effects of amplification on speech-recognition performance in the aided ears of monaurally and binaurally fitted subjects. Subjects consisted of 19 monaurally aided adults, 28 binaurally aided adults, and 19 control adults. Both ears of the experimental subjects (binaurally and monaurally aided adults) had BSSHI. The speech measures included the W-22 CID suprathreshold speech-recognition test, nonsense syllable test, and speech-perception-in-noise test. Initial testing was done between 6 and 12 weeks following hearing-aid fitting. Retests were performed approximately 1 year following the initial test. The results revealed that the mean aided minus unaided ear score for the nonsense syllable and W-22 tests increased significantly from the initial test to retest, reflecting a slight improvement in speech performance in the aided ear and a slightly greater decrement in the unaided ear. The findings were interpreted with respect to the theories of auditory deprivation and acclimatization.

Adult-onset auditory deprivation.

Adult-onset auditory deprivation following prolonged lack of amplification in the unaided ears of persons with bilaterally symmetrical sensorineural hearing impairment was first reported in 1984. This article on the phenomenon includes a review of the literature on adult-onset auditory deprivation in relation to etiology, pathophysiology, hearing-loss manifestations, typical audiologic profile, amplification strategies, contraindications or challenges to conventional hearing-aid fitting, and future research. A case study illustrates the phenomenon of auditory deprivation from monaural amplification with recovery following binaural amplification. The results of a complete audiologic and acoustic-immittance evaluation are presented for a bilaterally sensorineural hearing-impaired male with adult-onset auditory deprivation who initially was fit monaurally and later was fit binaurally. A significant decrement in the suprathreshold word-recognition scores occurred only in the unaided ear following monaural amplification, illustrating the phenomenon of adult-onset auditory deprivation. Following binaural amplification, the suprathreshold word-recognition scores for the formerly unaided ear improved significantly, illustrating the phenomenon of recovery from the adult-onset auditory deprivation with binaural amplification.

Effect of direction of pressure change on obtaining airtight seals in tympanometry.

To determine the effect of change in pressure direction on obtaining a seal during tympanometry, an ascending approach (-/+) was attempted when the traditional, descending approach (+/-) was unsuccessful in maintaining an airtight seal. Results revealed that a seal was achieved using the ascending direction in twelve ears when the descending method failed; in only four ears, neither method was successful.

Cyclic AMP receptor protein of E. coli: its role in the synthesis of inducible enzymes.

A cyclic AMP binding protein has been purified over 100-fold from E. coli extracts. Protein purified from wild-type strains binds cyclic AMP with an apparent dissociation constant of 1-2 x 10(-6)M. Two mutant strains that are unresponsive to exogenous cyclic AMP have altered binding activity; the protein purified from one of these mutants has a decreased affinity for cyclic AMP (apparent dissociation constant = 2 x 10(-5)M). Extracts of this mutant are deficient in their ability to support beta-galactosidase synthesis in vitro. The addition of purified, wild-type binding protein to these extracts restores enzyme synthesis toward normal. Because this binding protein appears to be required for cyclic AMP action, we suggest it be called the cyclic AMP receptor protein (CR protein).