Search PubMed⌕ Search

Biomedical subjects

D Henderson

Publications and source records attributed to D Henderson.

At least 109 records · Page 6Linked to original sources
PubMed1997

Evidence that inner hair cells are the major source of cochlear summating potentials.

The role of the inner hair cells (IHCs) in generating the cochlear summating potentials (SP) was assessed by measuring SP, cochlear nerve action potentials (CAP), cochlear microphonics (CM) and 2f1-f2 distortion product otoacoustic emissions (DPOAEs) in 15 chinchillas with either acute chemical de-afferentation, accomplished by applying kainic acid to the round window, or surgical de-afferentation and basal IHC loss, which developed within two months after sectioning the auditory nerve. In the auditory nerve sectioned ears, type I ganglion cells disappeared whereas most, if not all, type II ganglion cells were still present. Histological analysis of surface preparations and sections through the modiolus verified the de-afferentation in both models and showed a large IHC loss at the base of the cochlea in the ears with the auditory nerve sectioned while other structures of the cochlea remained intact. Unoperated (left) ears of 9 animals served as controls. CM and DPOAEs were normal in all ears whereas the CAP was substantially depressed in de-afferented ears. Comparisons among the SP input-output functions suggest that (1) the IHCs are the major generator of SP recorded from the round window in chinchilla, in particular at low to moderate stimulus levels, (2) the SP recorded from the round window largely reflects the responses from hair cells at the base of the cochlea, and (3) kainic acid results in an increase of SP amplitude to high-level stimuli whereas the SP to low- to moderate-level stimuli remains in the normal range.

Acoustic Stimulation↗
PubMed1997

R-phenylisopropyladenosine attenuates noise-induced hearing loss in the chinchilla.

Reactive oxygen species, which are cytotoxic to living tissues, are thought to be partly responsible for noise-induced hearing loss. In this study R-phenylisopropyladenosine (R-PIA), a stable non-hydrolyzable adenosine analogue which has been found effective in upregulating antioxidant enzyme activity levels, was topologically applied to the round window of the right ears of chinchillas. Physiological saline was applied to the round window of the left ears (control). The animals were then exposed to a 4 kHz octave band noise at 105 dB SPL for 4 h. Inferior colliculus evoked potential thresholds and distortion product otoacoustic emissions (DPOAE) were measured and hair cell damage was documented. The mean threshold shifts immediately after the noise exposure were 70-90 dB at frequencies between 2 and 16 kHz. There were no significant differences in threshold shifts at this point between the R-PIA-treated and control ears. By 4 days after noise exposure, however, the R-PIA-treated ears showed 20-30 dB more recovery than saline-treated ears at frequencies between 4 and 16 kHz. More importantly, threshold measurements made 20 days after noise exposure showed 10-15 dB less permanent threshold shifts in R-PIA-treated ears. The amplitudes of DPOAE also recovered to a greater extent and outer hair cell losses were less severe in the R-PIA-treated ears. The results suggest that administration of R-PIA facilitates the recovery process of the outer hair cell after noise exposure.

Adenosine↗
PubMed1997

Exploring novel chemotherapy treatments using the WWW.

A JAVA application, The Oncologists Workbench, which allows oncologists to estimate the influence of new cancer treatment schedules is being developed. The requirement for a rational approach to the design of chemotherapeutic regimens is well established [1]. Our prototype allows oncologists using the World Wide Web (WWW) to graphically construct treatment regimens while considering various toxic side effects. A simulation engine makes predictions of tumour growth based on previous clinical knowledge of response to treatment. The oncologist can then examine the predicted tumour response information with a specially constructed interactive viewer. These interlinked tools allow oncologists to develop and predict the effectiveness of novel chemotherapeutic regimens. This work is part of an ongoing collaboration between oncologists, mathematicians and computer scientists to provide tools for improving cancer chemotherapy.

Antineoplastic Agents↗
PubMed1997

Sputum cytology: a limited role.

AIMS: To determine the cost and sensitivity of sputum cytology in routine use and to determine when sputum cytology is most appropriate. METHODS: A retrospective study, based on all sputum cytology requests received in five histopathology/cytopathology laboratories in Yorkshire from 1 January to 31 December 1993. Cytology findings were correlated with histological diagnosis or clinical outcome, and related to the speciality of the referring clinician. RESULTS: Laboratory practice and performance was similar in all five centres. The average laboratory cost of sputum cytology was 26.93. The mean absolute sensitivity was 36% and the specificity was 99.6%. The majority of specimens was submitted by general physicians or geriatricians. The largest proportion of positive specimens were submitted by chest physicians. CONCLUSIONS: Often sputum cytology is used inappropriately as a screening investigation on, or soon after, admission. In addition, it is used inappropriately before bronchoscopy. Sputum cytology should be limited to individuals in whom a histological diagnosis is desired, but in whom bronchoscopy is inappropriate or unsuccessful.

Bronchoscopy↗
PubMed1997

Remote masking in noise-exposed chinchillas.

Remote masking (RM), the phenomenon whereby an intense high-frequency masker elevates thresholds for low-frequency signals, has been shown to be sensitive to various types of hearing loss in humans and to temporary threshold shifts in chinchillas. In this experiment, RM was evaluated in chinchillas with permanent threshold shift (PTS). Thresholds for 0.5 and 1 kHz tones were measured in quiet and in the presence of an 88 dB SPL narrow band noise centered at 3 kHz in the animals exposed for 30 h to impact noise at 125 dB SPL as intensity. The results show that RM values are significantly lower in chinchillas with PTS than in normal hearing chinchillas.

Animals↗
PubMed1996

Effects of kainic acid on the cochlear potentials and distortion product otoacoustic emissions in chinchilla.

In absence of acoustic stimulation, the auditory nerve generates electrical noise with a spectral peak between 300 and 3000 Hz (Dolan et al., 1990). This electrical noise is eliminated when the dendrites of auditory nerve fibers are damaged by kainic acid (KA). We hypothesized that the KA-induced damage to the afferent dendrites might alter cochlear micromechanics or modify outer hair cell (OHC) electromotility. The KA-induced decrease in spontaneous electrical noise from the auditory nerve could conceivably reduce the spontaneous sounds recorded in the ear canal and the postulated change in cochlear micromechanics might alter distortion product otoacoustic emissions (DPOAE). To evaluate these hypotheses, we applied KA to the round window of the cochlea. KA reduced the spontaneous electrical noise recorded from the round window and significantly reduced the amplitude of the compound action potential (CAP) to tone bursts at 2, 4 and 8 kHz. KA caused only a slight reduction in the amplitude of the cochlear microphonic (CM) recorded from the round window: however, it had no effect on the spontaneous acoustic noise in the car canal or on 2 f1-f2 DPOAEs. These results suggest that the KA-induced reduction of electrical noise from the auditory nerve has no measurable effect on OHC electromotility as reflected in spontaneous otoacoustic emissions and that damage to the afferent dendrites has no effect on cochlear micromechanics as reflected in DPOAEs.

Acoustic Stimulation↗
PubMed1996

Minimally invasive therapies in the treatment of erectile dysfunction in anticoagulated cases: a study of satisfaction and safety.

PURPOSE: We evaluated patient satisfaction with and the safety of vacuum therapy and self-injection during warfarin treatment of impotent men. MATERIALS AND METHODS: In a 24-week prospective study 33 patients were assigned to vacuum therapy or intracavernous injections with crossover at 12 weeks. Patients maintained diaries, and were followed with physical examinations, coagulation studies and questionnaires. RESULTS: Of the 33 patients 26 completed the study with 706 vacuum applications (mean 1.9 weekly) and 605 injections (mean 1.6 weekly). There are 11 acute minor complications with vacuum therapy (petechiae that resolved spontaneously) and no chronic complications. Only quality of climax was diminished with vacuum therapy. Self-injection resulted in acute minor complications (3 ecchymoses and 1 prolonged erection requiring intervention) and 1 chronic complication (corporeal fibrosis with mild curvature). CONCLUSIONS: The adverse effects of vacuum therapy and intracavernous self-injection in patients on warfarin do not exceed the rate in the general urological population. These therapies appear to be safe in patients receiving warfarin.

Alprostadil↗
PubMed1996

Time-based lag sequential analysis and the functional assessment of challenging behaviour.

This paper describes the application of time-based lag sequential analysis to the functional assessment of challenging behaviours shown by people with severe learning disabilities. The potential uses of the approach are illustrated with regards to identifying: (1) aspects of the stimulus control of challenging behaviour; (2) antecedents to the occurrence of challenging behaviour; and (3) the environmental consequences of challenging behaviour. The uses and limitations of the approach are discussed.

Adolescent↗
PubMed1996

Collaborative research by graduate students.

PURPOSE: Educators are challenged to prepare graduate students for future cooperative efforts by fostering collaboration. ORGANIZING FRAMEWORK: Assumptions and beliefs about collaborative research are examined and a definition and ethical considerations are suggested. A sample letter of agreement is also provided. CONCLUSIONS: Effective collaborative research is accomplished through planning and organization, and cannot be left to chance.

Alberta↗
PubMed1996

The primase of broad-host-range plasmid R1162 is active in conjugal transfer.

The broad-host-range plasmid R1162 is conjugally mobilized at high frequency by the IncP-1 plasmid R751 but is poorly mobilized by pOX38, a derivative of the F factor. In both cases, the origin of transfer (oriT) and the Mob proteins of R1162 are required, indicating that these plasmids are mobilized by similar mechanisms. R1162 encodes a primase, essential for vegetative replication of the plasmid, that is made both as a separate protein and as the carboxy-terminal domain of MobA, one of the R1162 mobilization proteins (P. Scholz, V. Haring, B. Wittman-Liebold, K. Ashman, M. Bagdasarian, and E. Scherzinger, Gene 75:271-288, 1989). When R751 is the mobilizing vector, the primase is not required for mobilization of plasmids containing cloned mob-oriT R1162 DNA. However, detectable mobilization of such plasmids by pOX38 requires both the primase and its cognate initiation site, oriented for synthesis of the complement to the transferred strand. The long form of the primase is required for optimal transfer: R1162 replicons lacking this form also are not transferred detectably by pOX38 and are less well mobilized by R751. The distance between oriT and the primase initiation site affects the frequency of mobilization, and this effect is polar in the direction of transfer. Our results indicate that the R1162 primase is active in mobilization of R1162 and suggest that the MobA-linked form is an adaptation increasing its effectiveness during transfer.

Conjugation, Genetic↗
PubMed1996

Some drug-resistant models for cancer chemotherapy. Part 1: Cycle-nonspecific drugs.

The pioneering mathematical analyses for describing the phenomenon of clonal selection, whereby cancer cells mutate and become resistant to treatment, were carried out by Goldie & Coldman (1979, 1983). The present analysis yields more generalized drug-resistant models arising in chemotherapy treatment when cycle-nonspecific (CNS) drugs (i.e. drugs which are toxic to cells irrespective of their position in the cell cycle) are deployed. This is accomplished by modifying models developed by Wheldon (1988) and Usher (1994) for investigating the effect of chemotherapy drugs on homogeneous cell populations (i.e. in the absence of drug resistance); both types of migration, of drug-sensitive cells to drug-resistant cells, and the possibility of a migration of drug-resistant cells to drug-sensitive cells, are incorporated into the models. Subsequently, drug concentrations are sought such that both the drug-resistant cell subpopulation and the drug-sensitive cell subpopulation either simultaneously decay or remain of constant size. The analysis reveals that the role played by the migration of drug-resistant cells to drug-sensitive cells is significant, if it occurs, when seeking appropriate drug concentrations. The qualitative results from these models provide further insight into the effective treatment of cancer by chemotherapy in the presence of drug resistance.

Antineoplastic Agents↗
PubMed1996

A novel G protein-coupled P2 purinoceptor (P2Y3) activated preferentially by nucleoside diphosphates.

A partial cDNA was isolated by hybridization screening of an embryonic chick brain library for P2Y purinoceptors. After extension to full length, it revealed an open reading frame that encoded a protein, P2Y3, of 328 amino acids that is nearest in sequence identity to the G protein-coupled P2 purinoceptors obtained by DNA cloning. Expression of P2Y3 in cRNA-injected Xenopus oocytes confirmed that this cDNA encodes a member of the metabotropic purinoceptor family, with a novel order for the relative activities of nucleotides. At 100 microM concentrations, ADP gave the highest activity, and UTP and UDP were also strongly active. When expressed in the human T cell line Jurkat, P2Y3 mediated transient increases in intracellular Ca2+ in response to various nucleotides. Again, an unusual agonist rank order was revealed, with uridine nucleotides being more potent than adenosine nucleotides and UDP being the most potent agonist tested (half-maximal concentration, 0.13 microM) and 10-fold more potent than UTP. 2-Methylthlo-ATP was of relatively low activity in both systems. The receptor transcript is expressed in brain, spinal cord, kidney, and lung and is highly abundant in the spleen but not in other peripheral tissues that we tested. The results indicated that P2Y3 is a previously unknown P2 purinoceptor subtype with a preference for nucleoside diphosphates.

Adenosine Diphosphate↗
PubMed1996

Factors associated with staff support and resident lifestyle in services for people with multiple disabilities: a path analytic approach.

The quality and costs of residential services for 40 adults with severe learning disabilities and sensory impairments across four different service models were evaluated. A path analytic approach was used to calculate factors associated with four indicators of service quality: (1) assistance received by residents from staff; (2) positive contact received by residents from staff; (3) resident engagement in constructive activity; and (4) the level of physical integration of residents. The path analyses accounted for between 50 and 77% of the variance in the indicators. Factors found to be commonly associated with all four indicators included a community location, a specialized service orientation, the cognitive abilities of residents and a high level of scheduled activity. Service resources in the form of costs or staff ratios were not associated with any indicator of service quality. The findings strongly suggest an inverse system of care in that residents with greater skills receive more staff support. The implications of these and other findings for further research and service practice are discussed.

Adult↗