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Biomedical subjects

D Henderson

Publications and source records attributed to D Henderson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Hearing loss following exposure during development to polychlorinated biphenyls: a cochlear site of action.

Maternal exposure to polyhalogenated hydrocarbons results in early postnatal hypothyroxenemia and a low-frequency hearing loss in adult offspring (Goldey et al., 1995a. Toxicol. Appl. Pharmacol. 135, 67-76; Herr et al., 1996. Fundam. Appl. Toxicol. 33, 120-128). The purpose of the present work was to determine whether the site-of-action of this auditory impairment was within the cochlea. Primiparous Long-Evans rats were given daily oral doses of corn oil (control) or 8 mg/kg of the commercial PCB mixture Aroclor 1254 (A1254) from gestation day (GD) 6 through postnatal day (PND) 21. Auditory thresholds for 1-, 4-, 16-, and 40-kHz tones were assessed using reflex modification audiometry in young adult offspring on postnatal days (PND) 92-110. Approximately 6 weeks after auditory assessments, a subset of animals (n=4 per group) were killed for histological assessment of the cochlea. Surface preparations of the organ of Corti were prepared from one cochlea per animal and modiolar sections were prepared from the opposite cochlea. Consistent with previous findings, auditory thresholds for 1-kHz tones were elevated by approximately 25 dB in the A1254-exposed animals. Thresholds for all higher frequencies were not different compared to controls. Surface preparations of the organ of Corti revealed a mild to moderate loss of outer hair cells in the upper-middle and apical turns. Inner hair cells were not affected. Modiolar sections failed to reveal alterations in any other cochlear structures. There was also no apparent loss of ganglion cells. These data clearly link the loss of low-frequency hearing caused by exposure during development to A1254 to a loss of outer hair cells in the organ of Corti. The mechanism that underlies this developmental ototoxicity remains to be determined. These data provide the first evidence of a structural deficit in the nervous system of adult animals exposed to PCBs during development.

Animals↗
PubMed2000

Cochlear de-efferentation and impulse noise-induced acoustic trauma in the chinchilla.

The olivocochlear bundle (OCB) has been shown to protect the ear from acoustic trauma induced by continuous noise or tones. The present study examines the OCB's role in the ear's response to impulse noise (150 dB pSPL, 100 impulses, 50 s total exposure duration). Successful section of the OCB was achieved through a posterior parafloccular fossa approach for the right ears of six out of 15 adult chinchillas. The left ears from the same animals served as efferent-innervated controls. Measurements of inferior colliculus evoked potentials (ICPs) showed that the de-efferented ears incurred similar temporary and permanent threshold shifts as the control ears. Twenty days after noise exposure, depressed ICP amplitudes had virtually recovered to pre-values in the control ears whereas those in the de-efferented ears remained significantly depressed. Greater loss of inner hair cells was seen in the de-efferented ears than in the control ears. Both control and de-efferented ears incurred large loss of outer hair cells, with no statistically significant differences between groups. The current data are intriguing, yielding tentative evidence to suggest that inner hair cells of de-efferented ears are more susceptible to impulse noise than those in efferented control ears. In contrast, outer hair cell vulnerability to impulse noise appears to be unaffected by de-efferentation.

Acoustic Stimulation↗
PubMed2000

Cochlear microphonics and otoacoustic emissions in chronically de-efferented chinchilla.

The effects of eliminating the olivocochlear bundle (OCB) on cochlear electromechanical properties were examined by measuring cochlear microphonics (CM) and distortion product otoacoustic emissions (DPOAEs) in chronically de-efferented chinchillas. The OCB fibers to the right ears were successfully sectioned in six out of 15 adult chinchillas via a posterior paraflocular fossa approach. At the end of the experiment, these ears were histologically verified as being deprived of both lateral and medial OCB fibers. The opposite (left) ears from the animals served as controls. Following de-efferentation, changes of the inter-modulation distortion components (2f(1)-f(2), f(2)-f(1), 3f(1)-2f(2), 3f(2)-2f(1)) varied, depending on the frequencies and levels of the stimuli. DPOAE amplitudes to low-level stimuli were within the 95% confidence intervals around mean DPOAE amplitudes of the control ears at all the frequencies (1-8 kHz). At high stimulus levels, DPOAE amplitudes increased by 5-20 dB at 1 and 2 kHz while remaining in the normal range at 4 and 8 kHz. In contrast, the CM input/output functions to stimuli from 1 to 8 kHz were significantly reduced by approximately 40-50% at all input levels. The results suggest that the OCB may play a role in modulating electrical properties of the outer hair cells and in reducing the magnitude of cochlear distortion to high-level stimuli.

Acetylcholinesterase↗
PubMed2000

Risk behaviours for HIV and hepatitis infection among anabolic-androgenic steroid users.

This study examined HIV and hepatitis risk behaviours among anabolic-androgenic steroid (AAS) users and controls, providing a detailed assessment of both injection and sexual practices. Fifty AAS-using and 40 non-AAS-using weight trainers completed a semi-structured interview followed by a detailed questionnaire. The 'high risk' behaviour of sharing needles and syringes was not current practice among the AAS-using sample, with only one user reporting sharing injecting equipment in the past. However, for some users it was common practice to share multi-dose vials (19%) and to divide drugs using syringes (17%). Both these practices are potential routes for HIV and hepatitis infection. Significantly more AAS users (36%) reported increases in sex drive over the last three months than did the control subjects (5%). More AAS users than controls were engaging in sex with more than one partner while infrequently using condoms. These findings support the maintenance of needle exchange schemes which are essential to continued safe injecting practices among AAS users. The elevated sexual risk behaviour of AAS users could be due to AAS's effect of increasing sex drive or to a 'risk taking' personality trait among AAS users.

Adolescent↗
PubMed2000

Erythrocyte transfusion causes immunosuppression after total hip replacement.

A prospective study of 34 patients undergoing total hip replacement was done to determine whether homologous erythrocyte transfusion causes postoperative immunosuppression. In the transfused patient group (14 patients), there was a reduction in CD3+ and CD3+4+ cell numbers at Day 2, returning to preoperative levels by Day 7. In contrast, in the untransfused patient group (20 patients), there was no significant depression in these lymphocyte subgroups at Day 2 and an increase in total lymphocyte, CD3+, CD3+4+, and CD3+4-8- cell numbers at Day 7. In both patient groups there was postoperative leukocytosis, granulocytosis, and monocytosis at Days 2 and 7, with no significant change in postoperative B (CD19+) cell numbers, natural killer cells, or the minor T cell populations of CD3+4+8+ and CD3+25+. The lymphocyte functional test of Candida recall was significantly impaired at Day 7 in the transfused patient group, where Candida recall is a memory T cell response to an antigen extracted from the yeast Candida Albicans. These findings suggest that homologous erythrocyte transfusion after hip replacement surgery causes cell mediated immune suppression. The main clinical implication of the current study is that perioperative homologous erythrocyte transfusion may place patients at greater risk of infectious complications, including infection of the prosthesis.

Arthroplasty, Replacement, Hip↗
PubMed2000

Density-functional theory for an electrolyte confined by thin charged walls.

Results are reported for the primitive model of an electrolyte and for the solvent primitive model of an electrolyte for the case where these fluids are confined by two charged walls. When the walls are thin, the confined electrolyte inside the walls is affected by the charge on both the inside and the outside of the walls. In the case of the primitive model (PM), this system has been studied previously using a singlet integral equation. Our density-functional (DF) study is more general because the fluids inside and outside the walls are constrained to have the same chemical potential and because solvent effects are considered, albeit at a crude level. The singlet integral equation does not consider the chemical potential constraint explicitly. We find that for the low density PM, the DF and integral equation approaches yield, except for a very narrow pore, very similar results. When solvent molecules are considered, the profiles become oscillatory. The co-ion density profiles are particularily interesting because the repulsive electrostatic potential and the effect of the increased pressure in "pushing" the co-ions against the wall compete.

Electrolytes↗
PubMed2000

Structure of charged colloids under a wedge confinement

Monte Carlo simulations have been performed to study the influence of a wedge confinement by hard walls on the ordering of charged colloidal particles interacting through screened Coulomb repulsive potential in an aqueous medium. The density distribution of particles for a fixed wedge angle straight theta(0) is studied for different suspension parameters, viz., bulk volume fraction straight phi, salt concentration C(s), and charge Ze on the particles. The density distribution rho(straight theta) along the angular direction and that along the radial direction, rho(r), have been analyzed in different regions of the wedge. Simulations show the formation of layered structure along the angular direction and a large gathering of particles along the wall. The number of layers as well as the density of particles within the layer are found to change as the strength and range of the interaction are varied, whereas the density profiles calculated close to the vertex region showed no significant variation in the density. The radial density profiles rho(r) corresponding to the vertex region show one-dimensional (1D) ordering of particles parallel to the vertex at a distance that is close to a wedge height, h equal to diameter of the particle. This 1D ordering is found to be destroyed upon the addition of salt or lowering the straight phi. The reported experimental observations on the "vacuum phase" are discussed in the light of the present results.

Journal Article↗
PubMed2000

Comment on "Algebraic perturbation theory for polar fluids: A model for the dielectric constant"

Kalikmanov [Phys. Rev. E 59, 4085 (1999)] proposed a perturbation theory method to calculate the dielectric constant of dipolar hard sphere fluids using an infinitely long cylindrical container to avoid the depolarization. We demonstrate that while the method is very helpful, his theory appears to be incomplete because of the incorrect calculation of the corresponding three-body integrals. It is shown that with the correct consideration of these terms the theory is consistent with the results of earlier work in low-density limit, and at high densities the method yields the equation of Tani et al. [Mol. Phys. 48, 863 (1983)] for the dipolar hard sphere fluid dielectric constant.

Journal Article↗
PubMed2000

Intubation conditions and postoperative myalgia in outpatient dental surgery: a comparison of succinylcholine with mivacurium.

Ninety-four patients undergoing elective outpatient third molar extraction were recruited into a double-blind, randomized, prospective trial comparing mivacurium (group M) with succinylcholine (Group S) for conditions for endotracheal intubation and the occurrence of postoperative myalgia. Anaesthesia was induced with fentanyl 1 microgram.kg-1 and propofol 2.5 micrograms.kg-1 in all patients. Group S patients were given gallamine 20 mg while group M patients were given mivacurium 0.2 mg.kg-1. Manual ventilation was commenced and anaesthesia maintained with nitrous oxide 70% and isoflurane 1 to 2% in oxygen. After two minutes, group S patients were given succinylcholine 1.5 mg.kg-1 and group M patients 0.9% saline. Nasotracheal intubation was performed 30 seconds later. Intubating conditions in group M were significantly better than those in group S (P < 0.001). The incidence of postoperative myalgia was 9.5% in group M and 26% in group S but this was not statistically significant (P = 0.09). We propose that mivacurium is a suitable neuromuscular blocker to use for endotracheal intubation in outpatient dental surgery.

Adolescent↗
PubMed2000

Needs and opportunities for improving the health, safety, and productivity of medical research facilities.

Medical research facilities, indeed all the nation's constructed facilities, must be designed, operated, and maintained in a manner that supports the health, safety, and productivity of the occupants. The National Construction Goals, established by the National Science and Technology Council, envision substantial improvements in occupant health and worker productivity. The existing research and best practices case studies support this conclusion, but too frequently building industry professionals lack the knowledge to design, construct, operate, and maintain facilities at these optimum levels. There is a need for more research and more collaborative efforts between medical and facilities engineering researchers and practitioners in order to attain the National Construction Goals. Such collaborative efforts will simultaneously support attainment of the National Health Goals. This article is the summary report of the Healthy Buildings Committee for the Leadership Conference: Biomedical Facilities and the Environment sponsored by the National Institutes of Health, the National Association of Physicians for the Environment, and the Association of Higher Education Facilities Officers on 1--2 November 1999 in Bethesda, Maryland, USA.

Air Pollution, Indoor↗
PubMed2000

Generation of monospecific peptide antibodies to the DNA binding domain of p53.

The DNA binding domain (DBD) is the most mutated region of p53 in tumors and has proven to be relatively resistant to the generation of specific antibodies. Template assembled synthetic peptide (TASP) synthesis of a peptide derived from the DBD creates a highly immunogenic molecule without the need for large carriers such as keyhole limpet hemocyanin (KLH). In addition, a rapid means of generating monoclonal antibodies can be achieved through immunization in conjunction with ABL/MYC retrovirus injection into recipient mice. In this paper, we demonstrate that an antibody generated by this means, KH2, reacts specifically with the DBD of p53. To date, this is the first example of a peptide immunogen used successfully in ABL/MYC monoclonal antibody production. KH2 is also the first example of a monospecific antibody that directly binds to and, by definition, assumes the conformation of the DNA binding region of p53.

Amino Acid Sequence↗
PubMed2000

Intense noise-induced apoptosis in hair cells of guinea pig cochleae.

Cells can die by two distinct pathways: apoptosis and necrosis. To explore whether intense noise can induce hair cell (HC) death via the apoptotic pathway, we systematically examined morphological changes in guinea pig cochlear HC nuclei stained with Hoechst 33342, a fluorescent dye specifically labelling the nuclear DNA. A narrow band noise centred at 4 kHz with levels at 110 dB, 115 dB or 120 dB (SPL) was applied for 4 h and the exposed cochleae were collected at various intervals (3 h, 3 or 14 days) after the noise exposure. Auditory function was monitored by measuring thresholds of auditory brain stem responses. In the noise-damaged cochleae, there were two major types of nuclear changes, nuclear condensation appeared as karyorrhexis or karyopyknosis and nuclear swelling. Karyorrhexis and karyopyknosis predominately appeared in the severely damaged cochlear region in the animals exposed to 120 dB noise and examined 3 h after the noise exposure. In contrast, swelling of nuclei occurred in all of the noise-exposed cochleae, and was the feature change in the animals exposed to 110 and 115 dB noise. This pathological change persisted at least for 14 days after the noise exposure. The typical changes of karyorrhexis and karyopyknosis noted in the animals exposed to 120 dB noise were morphologically similar to those nuclear changes described in previous studies for apoptosis, suggesting that the apoptotic process may be involved in intense noise-induced HC death.

Animals↗
PubMed1999

Selective loss of inner hair cells and type-I ganglion neurons in carboplatin-treated chinchillas. Mechanisms of damage and protection.

Carboplatin preferentially destroys inner hair cells (IHCs) and type-I spiral ganglion neurons while sparing outer hair cells (OHCs). Loss of IHCs and type-I ganglion cells is associated with a significant reduction of the compound action potential (CAP). However, the cochlear microphonic (CM) potential and distortion product otoacoustic emissions (DPOAEs) remain normal, indicating that the OHCs are functionally intact. In the vestibular system, carboplatin selectively destroys type-I hair cells and their afferent neurons. Damage of type-I vestibular hair cells and their afferent terminals is associated with significant depression of nystagmus induced by cold, caloric stimulation. Histochemical studies revealed a rapid decrease in succinate dehydrogenase (SDH) staining in IHCs soon after carboplatin treatment, and staining intensity remained depressed in surviving IHCs for at least 1 month after carboplatin treatment. These results suggest that carboplatin depresses the metabolic function in surviving IHCs. Several lines of evidence suggest that free radicals may contribute to carboplatin-induced sensory cell damage. Intracochlear infusion of L-buthionine-[S,R]-sulfoximine (BSO), which depletes intracellular glutathione (GSH), increases IHC and OHC loss. Previous in vitro studies have shown that neurotrophin 4/5 (NT-4/5) promotes the survival of spiral ganglion neurons from cisplatin ototoxicity. In vivo perfusion of NT-4/5 promoted the survival of spiral ganglion neurons, but did not protect the hair cells.

Action Potentials↗
PubMed1999

A radical demise. Toxins and trauma share common pathways in hair cell death.

The pathologic similarities noted after ototoxic and/or traumatic injury to the cochlea as well as the key features of the cochlea that make it susceptible to reactive oxygen species (ROS) damage are reviewed. Recent evidence linking ROS to cochlear damage associated with both ototoxins and/or trauma are presented. Mechanisms of generation of ROS in the cochlea and how these metabolites damage the cochlea and impair function are also reviewed. Finally, examples of novel therapeutic strategies to prevent and reverse hearing loss due to noise and/or ototoxins are presented to illustrate the clinical relevance of these new findings.

Aminoglycosides↗
PubMed1999

Recovery of kainic acid excitotoxicity in chinchilla cochlea.

The present study examines the recovery of the inner hair cell (IHC)/auditory nerve synapse following cochlear excitotoxicity induced by kainic acid (KA). Three hours after KA treatment, there was massive swelling of type I afferent endings under the IHCs. Five to ten days later, the pattern of IHC innervation appeared to be normal. Distortion-product otoacoustic emissions were normal during the whole experiment. The amplitude of the auditory nerve compound action potential (CAP) was significantly reduced immediately after KA treatment and then recovered over a 30-day period. However, it only took five days for the evoked response from the inferior colliculus (IC) to recover from a substantial depression. In contrast to amplitudes, thresholds for the CAP and IC recovered at the same rate and returned to normal within 5 days after KA. Single auditory nerve fibers were also assessed at various times after the KA treatment. Ten days after KA, these fibers had almost normal thresholds, tuning, spontaneous, and driven discharge rates. The results indicate that (1) excitotoxically damaged cochlear afferent neurons can rapidly regenerate and establish viable synapses with the IHCs, and (2) the central auditory system recovers more rapidly than the periphery.

Action Potentials↗
PubMed1999

The role of antioxidants in protection from impulse noise.

The hearing loss from exposure to noise and ototoxic drugs share a number of audiological and pathological similarities. Recent research has shown that reactive oxygen species (ROS) may be a common factor in both noise- and drug-induced hearing loss. This review describes three experiments that point to ROS as a causative factor in both noise- and drug-induced hearing loss and antioxidants as a protective agent. In the first experiment, the ears of chinchillas were treated with R-N6-phenylisopropyladenoisine (R-PIA) and exposed to 150-dB impulse noise. The treated ears developed substantially less permanent hearing loss (PTS) and hair cell loss than the untreated ears. One interpretation of this experiment is that R-PIA increases the availability of glutathione (GSH). In the second experiment, the role of GSH was specifically examined. The ears of chinchillas were treated with glutathione monoethylester (GEE), a pro-GSH drug that has been shown to readily cross cell membranes and increase GSH levels. The GEE-treated ears had significantly less PTS and hair-cell loss than the nontreated ear. Previous research has shown that moderate levels of noise exposure can increase a subject's resistance to noise, and also increase the availability of antioxidant enzymes in the cochlea. In the third experiment, chinchillas were given a series of "toughening" exposures (i.e., 6 h of a 0.5-kHz OB noise at 95 dB for 10 days). After the series of "toughening" exposures, the subjects were treated with carboplatin, a drug that causes massive inner-hair-cell lesions in the chinchilla. The animals receiving the 10-day toughening exposure developed less PTS and hair-cell loss than the control animals.

Animals↗