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Biomedical subjects

S Freeman

Publications and source records attributed to S Freeman.

232 records · Page 13Linked to original sources

Short and middle latency vestibular evoked responses to acceleration in man.

We have succeeded in recording short and middle latency vestibular evoked responses in human subjects. The head was held rigidly in a special, patented head holder, constructed individually for each subject, which gripped the teeth of the upper jaw. The stimulus consisted of 2/sec steps of angular acceleration impulses produced by a special motor with intensities of about 10,000 degrees/sec 2 and with a rise time of 1-2 msec. The electrical activity was recorded as the potential difference between special forehead and mastoid electrodes having a large, secure contact area with the skin. The activity was digitally filtered and averaged in 2 separate channels by means of a Microshev 2000 evoked response system. The short latency responses, with peaks at about 3.5 msec (forehead positive), 6.0 msec (forehead negative) and 8.4 msec (forehead positive; bandpass: 200-2000 Hz; average of 1024 trials), had amplitudes of about 0.5 microV. The middle latency responses had peaks at about 8.8 msec (forehead positive), 18.8 msec (forehead negative) and 26.8 msec (forehead positive; 30-300 Hz; N = 128 trials), with larger amplitudes (about 15 microV). These responses were consistently recorded in the same subject at different times and were similar in different normal subjects. Strenuous control experiments were conducted in order to ensure that these responses are not artefacts due to the movement of conducting media (head, electrodes and leads) in the electromagnetic field of the motor and are elicited by activation of normal labyrinths.(ABSTRACT TRUNCATED AT 250 WORDS)

Acceleration↗

Atriopeptin prevents angiotensin II-stimulated glucose utilization in the subfornical organ.

Previous studies have shown that angiotensin II (ANG II) increases glucose utilization in the subfornical organ and stimulates drinking behavior. We investigated with the deoxyglucose method whether atriopeptin III, an atrial natriuretic peptide (ANP), would prevent this enhanced glucose metabolism and interfere with the drinking response in the presence of ANG II. Two rat models with high circulating levels of ANG II were studied: the homozygous Brattleboro and ANG II-infused Sprague-Dawley rats. ANP decreased the normally enhanced glucose utilization in the subfornical organ in the Brattleboro rat and inhibited ANG II-stimulated glucose metabolism in the subfornical organ of Sprague-Dawley rats. This effect was accompanied by decreased ANG II-stimulated water intake. These findings indicate that ANP may act at the level of subfornical organ to antagonize the dipsogenic action of ANG II.

Angiotensin II↗

Sequence polymorphism of HLA DR beta 1 alleles relating to T-cell-recognized determinants.

HLA class II molecules are a highly polymorphic family of dimeric cell-surface proteins primarily involved in regulating T-cell responses to extrinsic antigens. To define regions of class II molecules involved in T-cell recognition, we have now compared sequences of three HLA DR beta cDNA clones obtained from cells that all express the same serologically defined determinants but differ in terms of T-cell-recognized specificities. The comparisons indicate that very few (one to four) nucleotides differ between what are almost certainly alleles of the DR beta 1 locus. All differences were in the first domain of the molecule and all localized to a region from amino acids 71-86. Because all differences were found only in this region of the molecule, and because DR alpha-chains seem to be relatively non-polymorphic, these positions in the DR beta-chain must have a major role in influencing T-cell recognition of the DR molecule.

Alleles↗

Development of transient evoked otoacoustic emissions in the neonatal rat.

Otoacoustic emissions (OAEs) represent acoustic energy generated by the cochlear amplifier which contributes to auditory sensitivity and frequency discrimination. Therefore the OAEs can serve as a noninvasive tool to study the cochlear amplifier. While transient evoked OAEs (TEOAEs) are generally recorded clinically in man, it has been difficult to record them in animals and instead cubic distortion product OAEs (DPOAEs) have been experimentally studied in animals. In a previous study, we perfected a method of recording TEOAEs routinely in rats and this technique was used here to study the development of OAEs in neonatal rats. TEOAEs were recorded and compared to the DPOAEs on several postnatal days. With increasing postnatal age, TEOAE peak-to-peak amplitude and spectral energy in the 2- to 4-kHz band increased, their threshold decreased and their input-output functions became less monotonic with a change in slope (notch and/or plateau) in the mid-intensity region. The DPOAEs to higher frequencies appeared first, then the TEOAEs, followed by the DPOAEs to lower frequencies. With age, their amplitude also increased, thresholds decreased and a notch appeared in their input-output functions. The TEOAEs were measurable during the continuum of the appearance of the DPOAEs and the developmental sequences of both types of OAEs were similar. This may be evidence that similar mechanisms account for their maturation which probably initially involves a reduction in the air-bone gap with maturation of the outer and middle ears, and then elevation of the endocochlear potential and additional micromechanical maturations.

Age Factors↗

Effect of temperature on the transient evoked and distortion product otoacoustic emissions in rats.

In order to study the energy dependence of the cochlear amplifier, transient evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs) were recorded in rats during gradual cooling to 27 degrees C and heating to 40 degrees C. In the range 33-39 degrees C, the TEOAEs and DPOAEs were maximal in amplitude and almost insensitive to temperature. However, they were significantly depressed (reversibly) at higher and lower temperatures. Intensity functions were plotted at 37, 27 and 40 degrees C for both types of oto-acoustic emissions. At 37 degrees C intensity functions were nonlinear, with a notch at mid-intensity regions. At 27 degrees C, the magnitudes were depressed more at the lower intensities and threshold elevations were observed. As a result, the intensity functions were more linear and the notch was no longer seen. This result provides further evidence for a more active, energy-dependent component of the otoacoustic emissions at lower intensities for both TEOAEs and DPOAEs. The cooling probably affects the lower intensity otoacoustic emissions by inducing a depression in the endocochlear potential, by reducing the motility of the outer hair cells and by introducing a small conductive hearing loss.

Animals↗

Effect of long-term noise exposure on the developing and developed ear in the Rat.

There have been reports that the developing ear is more sensitive than the adult ear to noise-induced hearing loss. This was investigated by testing auditory function in rats, both electrophysiologically and histologically, following exposure to broad-band noise (12 h/day for 15 days) at different stages of auditory development (neonates and adults), and also in age-matched controls. An exposure of 90 dB SPL broad-band noise caused no long-term change in auditory function in either age group. A higher exposure (102 dB SPL) caused greater long-term changes in hearing in the adult compared to the young noise-exposed rats, although histology showed greater damage to hair cells in the younger animals. Therefore, functionally, the developing ear does not seem more vulnerable than the developed ear to acoustic trauma.

Age Factors↗

The effect of various durations of noise exposure on auditory brainstem response, distortion product otoacoustic emissions and transient evoked otoacoustic emissions in rats.

This study was designed to investigate the effect of various durations of noise exposure in animals on physiological responses from the cochlea which are also used clinically in humans: auditory brainstem response (ABR), transient evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs). Rats were exposed to 113 dB SPL broad-band noise (12 h on/12 h off) for durations of 3, 6, 9, 12, 15 and 21 days, and tested 24 h after cessation of the noise and again after a period of 6 weeks. ABR threshold to click stimuli and to a 2-kHz tone burst (TB), TEOAE energy content and DPOAE amplitude in the exposed rats were compared to those in a group of control rats not exposed to noise. ABR thresholds (click and TB) were significantly elevated in all exposure duration groups compared to control rats. DPOAE amplitudes and TEOAE energy content were significantly reduced. The mean ABR thresholds following 21 days exposure were significantly greater (click = 100 dB pe SPL; TB = 115 dB pe SPL) than those following 3 days exposure (click = 86 dB pe SPL; TB = 91 dB pe SPL). Linear regression analysis between recorded responses and duration of noise exposure (days) showed a significant increase in ABR thresholds of approximately 0.8-- 1.4 dB/day. TEOAE and DPOAE responses showed no such dependence on noise duration and were already maximally reduced after only 3 days of exposure. This can be explained by the possibility that short noise exposures may cause damage to the early, more active stages of cochlear transduction (as shown by TEOAEs and DPOAEs). As the noise exposure continues, further damage may be induced at additional, later stages of the cochlear transduction cascade (as shown by ABR). Thus, ABR seems more sensitive to noise duration than OAE measures.

Animals↗

The pathway enabling external sounds to reach and excite the fetal inner ear.

The human fetus in utero is able to respond to sounds in the amniotic fluid enveloping the fetus after about 20 weeks gestation. The pathway by which sound reaches and activates the fetal inner ear is not entirely known. It has been suggested that in this total fluid environment, the tympanic membrane and the round window membrane become 'transparent' to the sound field, enabling the sounds to reach the inner ear directly through the tympanic membrane and the round window membrane. It is also possible that sounds reach the inner ear by means of tympanic membrane--ossicular chain--stapes footplate conduction (as in normal air conduction). There is also evidence that sounds reach the fetal inner ear by bone conduction. Several animal and human models of the fetus in utero were studied here in order to investigate the pathway enabling sounds to reach and activate the fetal inner ear. This included studying the auditory responses to sound stimuli of animals and humans under water. It was clearly shown in all the models that the dominant mechanism was bone conduction, with little if any contribution from the external and middle ears. Based on earlier experiments on the mechanism and pathway of bone conduction, the results of this study lead to the suggestion that the skull bone vibrations induced by the sound field in the amniotic fluid enveloping the fetus probably give rise to a sound field within the fetal cranial cavity (brain and CSF) which reaches the fetal inner ear through fluid communication channels connecting the cranial cavity and the inner ear.

Animals↗

The neonate has a temporary conductive hearing loss due to fluid in the middle ear.

Postnatal functional changes in the activity of the ear and auditory pathway in neonatal guinea pigs [from day of birth (postnatal day, PND = 0), PNDs 1-4, 7 and then weekly up to 7 weeks] were studied as a model of maturation of hearing in human neonates. On the day of birth there were signs of a conductive hearing loss: negative middle ear pressure, auditory nerve brainstem evoked response (ABR) threshold elevation, ABR wave 1 latency prolongation and low amplitude otoacoustic emissions. The conductive hearing loss is probably a result of the (amniotic) fluid found in the neonatal middle-ear cavity. Over the next PNDs, this conductive hearing loss was resolved. In order to confirm this neonatal conductive hearing loss and its resolution, saline was instilled into the middle ear of guinea pigs. This induced signs of a conductive hearing loss similar to those seen in the neonatal guinea pigs which disappeared with clearance of this fluid. Therefore it may be concluded that most of the changes in auditory function seen over the first PNDs are due to absorption of amniotic fluid from the middle-ear cavity.

Acoustic Impedance Tests↗

The importance of thyroid hormone for auditory development in the fetus and neonate.

It seems that many auditory maturational events are regulated by thyroid hormone since elevation in thyroid hormone level always precedes the onset of hearing in the fetus-neonate; low thyroid activity in the developing human fetus or rat neonate leads to hearing loss; earlier, elevated thyroid levels in rat neonate lead to earlier onset of hearing. The hormone, bound to its receptors in the nucleus, acts as a transcription factor activating genes which lead to the synthesis of several proteins and enzymes involved in the structural and functional development of many tissues (e.g. brain, heart, kidney, skeletal muscle) including the ear. Several types of congenital hearing loss of unexplained etiology may be due to abnormalities in one or more stages of this gene cascade since several types of congenital hearing loss have been shown to involve defects in genes related to these events.

Animals↗

Transient evoked otoacoustic emissions in newborns in the first 48 hours after birth.

Newborns are often discharged from hospital at the age of about 48 hours. At this age, transient evoked otoacoustic emissions (TEOAEs) are not necessarily recordable in all healthy newborns. In order to determine the factors which would enable the successful recording of TEOAEs before discharge to facilitate screening for hearing, 65 fullterm newborns under 48 hours of age were tested, the youngest being 10 hours old. The ears of those neonates in whom TEOAEs could not be obtained (N = 7 neonates bilaterally, 6 unilaterally) were examined otoscopically, cleaned of vernix and retested for TEOAEs. We were thus able to record in at least one ear in all neonates tested, if the ears were clean, if they were asleep and if the testing room was quiet.

Acoustic Stimulation↗

Transient evoked otoacoustic emissions in laboratory animals.

Transient evoked otoacoustic emissions (TEOAEs) are much used clinically. However, it has been difficult to record them in small laboratory animals, and experimental manipulations designed to determine the generation mechanisms of this type of emission could not be performed. After refining the technique, based on the use of short clicks and a short amplifier gain suppression period, TEOAEs were recorded using the same instrumentation and techniques in rabbits, Psammomys obesus (fat sand rats), mice, rats and guinea pigs. Distortion product emissions were also recorded. The responses in each species differed with respect to threshold, magnitude, frequency spectrum and duration (endpoint). The ability to record TEOAEs routinely in laboratory animals should now allow for further experimentation on the mechanisms of their generation, on the cochlear amplifier in general and on the comparison of TEOAEs with distortion product emissions in individual species and animals.

Acoustic Stimulation↗

Cushing's syndrome secondary to olfactory neuroblastoma.

A case of olfactory neuroblastoma in a 36-year-old woman who presented with florid Cushing's syndrome is reported. A nasal polyp, which proved to be an olfactory neuroblastoma, was resected. The procedure was followed by complete remission from the endocrinologic abnormalities. Postoperatively, the patient was well for 5 years until recurrence of both Cushing's syndrome and the nasal polyp was noted. Following combined transnasal-transcranial resection of the tumor, which extended into the anterior cranial fossa, the patient again experienced complete remission of Cushing's syndrome. Immunohistochemistry showed the tumor to be positive for neuron-specific enolase, synaptophysin, chromogranin, adrenocorticotropic hormone, beta-endorphin, and S-100 protein. Electron microscopy revealed neuritic processes containing microtubules and neurosecretory granules. This is the first reported case of Cushing's syndrome secondary to olfactory neuroblastoma.

Adult↗

Measuring services: a district nursing dependency tool.

The government has highlighted the importance of reducing inequalities in health and providing an equal and high quality service to all patients. The district nursing service in Wolverhampton monitors the provision of services across the town to ensure high quality care for all patients.

Activities of Daily Living↗