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Biomedical subjects

S E Smith

Publications and source records attributed to S E Smith.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of normobaric hypoxia on auditory sensitivity.

Previous psychophysical studies of hypoxia's effects on auditory sensitivity have provided mixed results but the weight of evidence supports the conclusion that sensitivity is unaffected by hypoxia. This conclusion is discrepant with that drawn from physiological studies in which hypoxia has been found to affect auditory-evoked response (AER) latency. One possible explanation of this discrepancy concerns the relatively low maximum frequency (8 kHz) for which hypoxia's effects were assessed in the psychophysical studies. We have extended the range of frequencies over which hypoxia's effects have been examined to include frequencies up to 16 kHz. Thresholds for 1-, 8-, 10-, 12-, 14- and 16-kHz tones were measured at levels of hypoxia equivalent to altitudes of 0, 1,200, 2,400 and 3,700 m. Our results indicate that sensitivity for frequencies up to 16 kHz is unaffected by hypoxia. We suggest that AER latency does not provide a valid measure of auditory sensitivity.

Adult↗
PubMed2000

Effect of normobaric hypoxia on sound localization.

BACKGROUND: Three-dimensional (3D) audio displays have considerable potential for conveying spatial information in the aviation environment. How reliably these displays will function in that environment will depend in part on the extent to which sound localization is affected by hypoxia. Many aircraft systems operators are routinely exposed to mild hypoxia, and all are at risk of exposure to more severe hypoxia. METHODS: We have examined hypoxia's effect on localization by measuring the localization performance of four subjects exposed to simulated altitudes of 0, 1200, 2400 and 3700 m above sea level for about 30 min. Sounds to be localized were presented from a free-field source at locations covering 360 degrees of azimuth and extending from -47.6 to + 80 degrees elevation. RESULTS: Localization performance was statistically indistinguishable across the altitudes tested. Average localization errors ranged from 12.6 degrees +/- 0.7 SE at 2400 m to 14 degrees +/- 0.84 SE at 0 m. CONCLUSION: The finding that hypoxia induced by exposure to simulated altitudes as high as 3700 m has no effect of sound localization is encouraging with respect to the continued development of 3D audio displays for use in the aviation environment.

Adult↗
PubMed1999

Expression of the heparan sulfate proteoglycan, perlecan, during mouse embryogenesis and perlecan chondrogenic activity in vitro.

Expression of the basement membrane heparan sulfate proteoglycan (HSPG), perlecan (Pln), mRNA, and protein has been examined during murine development. Both Pln mRNA and protein are highly expressed in cartilaginous regions of developing mouse embryos, but not in areas of membranous bone formation. Initially detected at low levels in precartilaginous areas of d 12.5 embryos, Pln protein accumulates in these regions through d 15.5 at which time high levels are detected in the cartilage primordia. Laminin and collagen type IV, other basal lamina proteins commonly found colocalized with Pln, are absent from the cartilage primordia. Accumulation of Pln mRNA, detected by in situ hybridization, was increased in d 14.5 embryos. Cartilage primordia expression decreased to levels similar to that of the surrounding tissue at d 15.5. Pln accumulation in developing cartilage is preceded by that of collagen type II. To gain insight into Pln function in chondrogenesis, an assay was developed to assess the potential inductive activity of Pln using multipotential 10T1/2 murine embryonic fibroblast cells. Culture on Pln, but not on a variety of other matrices, stimulated extensive formation of dense nodules reminiscent of embryonic cartilaginous condensations. These nodules stained intensely with Alcian blue and collagen type II antibodies. mRNA encoding chondrocyte markers including collagen type II, aggrecan, and Pln was elevated in 10T1/2 cells cultured on Pln. Human chondrocytes that otherwise rapidly dedifferentiate during in vitro culture also formed nodules and expressed high levels of chondrocytic marker proteins when cultured on Pln. Collectively, these studies demonstrate that Pln is not only a marker of chondrogenesis, but also strongly potentiates chondrogenic differentiation in vitro.

Animals↗
PubMed1999

Bilateral Horner's syndrome: detection and occurrence.

OBJECTIVE: To develop a method for the detection of bilateral Horner's syndrome in patients with bilateral interruption of the cervical sympathetic pathway or widespread autonomic neuropathy. METHODS: Darkness pupil diameters and redilatation times during light reflexes have been recorded with infrared TV pupillometry in 65 healthy subjects, 47 patients with unilateral Horner's syndrome, and 20 patients with bilateral Horner's syndrome. The aetiologies of the last group were diabetic autonomic neuropathy (three cases), amyloidosis (four), pure autonomic failure (PAF) (four), dopamine-beta-hydroxylase deficiency (two), and one case each of hereditary sensory and autonomic neuropathy (HSAN) type III, carcinomatous sympathetic neuropathy, familial dysautonomia, multiple system atrophy, Anderson-Fabry disease, and anterior spinal artery thrombosis at C5,6 and one had had bilateral cervical sympathectomies. RESULTS: Darkness diameters on the affected side were below normal in 12 patients with unilateral Horner's syndrome, the measurement yielding only 26% sensitivity for detection of the condition. By contrast, the time taken to reach three quarter recovery in the light reflex (T3/4) was abnormally prolonged (redilatation lag) in 33 of the same eyes. The measurement yielded 70% sensitivity and 95% specificity for detection of the condition. In 20 cases, diagnosed on clinical grounds as having bilateral Horner's syndrome of various aetiologies, pupil diameters were abnormally small on both sides in five and on one side in three patients. Fourteen of these patients had significant redilatation lag in both eyes, five patients in one eye, and one patient had it in neither eye. Measurement of redilatation lag was therefore a more sensitive diagnostic test than pupil diameter in both unilateral and bilateral Horner's syndrome. CONCLUSIONS: Provided that the pupils are not tonic, bilateral Horner's syndrome can be diagnosed on the basis of redilatation lag. It occurs clinically in some generalised autonomic neuropathies and with interruption of the local sympathetic nerve supplies to the two eyes.

Adult↗
PubMed1999

Pupil abnormality in amyloidosis with autonomic neuropathy.

Darkness pupil diameters, light reflexes, and redilatation times have been recorded with infrared TV pupillometry in 12 consecutive patients with systemic amyloidosis associated with sensory motor and autonomic neuropathy. Nine of the patients had AL amyloidosis, two had familial amyloidosis associated with a transthyretin abnormality, and one was untyped. The pupils were abnormal in all 12 patients. On the basis of redilatation lag without pupillotonia, six patients had bilateral Horner's syndrome and in one of them amyloid deposits were found in a sympathetic ganglion and in the attached sympathetic chain obtained at necropsy. Four patients had bilateral tonic pupils with light-near dissociation and two had abnormally small pupils with reduced light reactions which could not be characterised. It seems that in patients with systemic amyloidosis generalised autonomic neuropathy is strongly associated with pupil abnormality as shown by tonic reactions with light-near dissociation, by redilatation lag, or by reduced size in darkness.

Adult↗
PubMed1999

Effect of divalent cations on AMPA-evoked extracellular alkaline shifts in rat hippocampal slices.

The generation of activity-evoked extracellular alkaline shifts has been linked to the presence of external Ca(2+) or Ba(2+). We further investigated this dependence using pH- and Ca(2+)-selective microelectrodes in the CA1 area of juvenile, rat hippocampal slices. In HEPES-buffered media, alkaline transients evoked by pressure ejection of RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) averaged approximately 0.07 unit pH and were calculated to arise from the equivalent net addition of approximately 1 mM strong base to the interstitial space. These alkaline responses were correlated with a mean decrease in [Ca(2+)](o) of approximately 300 microM. The alkalinizations were abolished reversibly in zero-Ca(2+) media, becoming indiscernible at a [Ca(2+)](o) of 117+/-29 microM. Addition of as little as 30-50 microM Ba(2+) caused the reappearance of an alkaline response. In approximately one-fourth of slices, a persistent alkaline shift of approximately 0.03 unit pH was observed in zero-Ca(2+) saline containing EGTA. In HEPES media, addition of 300 microM Cd(2+), 100 microM Ni(2+), or 100 microM nimodipine inhibited the alkaline shifts by roughly one-half, one-third, and one-third, respectively, whereas Cd(+) and Ni(2+) in combination fully blocked the response. In bicarbonate media, by contrast, Cd(+) and Ni(2+) blocked only two-thirds of the response. In the presence of bicarbonate, Ni(2+) caused an unexpected enhancement of the alkalinization by approximately 150%. However, when the extracellular carbonic anhydrase was blocked by benzolamide, addition of Ni(2+) reduced the alkaline shift. These results suggested that Ni(2+) partially inhibited the interstitial carbonic anhydrase and thereby increased the alkaline responses. These data indicate that an activity-dependent alkaline shift is largely dependent on the entry of Ca(2+) or Ba(2+) via voltage-gated calcium channels. However, sizable alkaline transients still can be generated with little or no external presence of these ions. Implications for the mechanism of the activity-dependent alkaline shift are discussed.

Animals↗
PubMed1999

Comparing pupil function with visual function in patients with Leber's hereditary optic neuropathy.

PURPOSE: To compare pupil function with visual function in patients with Leber's hereditary optic neuropathy (LHON) and age-matched normal control subjects. METHODS: Visual function was assessed by measuring the perceptual thresholds at five central locations in the visual field using automated static perimetry. Pupil function was assessed by recording the pupil responses to a standard intensity light stimulus (size equivalent to a Goldmann V target) presented at the same five locations in the visual field. The extent of the pupil afferent defect in LHON patients was quantified by establishing the relationship between stimulus intensity and the size of the pupil response in normal subjects and then interpolating the equivalent luminance deficit in LHON patients from the size of their pupil responses. RESULTS: At all five locations tested, the pupil responses were significantly reduced in amplitude, and the perceptual thresholds were significantly raised in LHON patients compared with normal control subjects. A nonparametric analysis of perceptual and pupil responses to perithreshold stimuli showed that a stimulus that was not perceived was three times more likely to be followed by a pupil response in a LHON patient than in a normal subject (P < 0.001). A quantitative comparison showed that the visual deficits exceeded the pupil deficits by on average 7.5 dB at all tested locations. CONCLUSIONS: Although both visual and pupil function are abnormal in LHON, there appears to be relative sparing of the pupil afferent fibers.

Adult↗
PubMed1999

Motion at the modular acetabular shell and liner interface. A comparative study.

Excessive polyethylene debris generated from a total hip arthroplasty can lead to osteolysis and premature revision. Most of this polyethylene debris comes from the concave articulation. However, abrasive wear on the convex side of a modular polyethylene component also may play a role in this problem. Motion of a modular polyethylene liner with respect to its shell can lead to such abrasive wear. Six samples of modular acetabular components from eight manufacturers were tested for motion between the shell and the liner. Motion at the shell liner interface was detected by five fiberoptic sensors in the x, y, and z planes. Micromotion occurred at the shell liner interface in all designs tested. The magnitude of motion varied between manufacturers, ranging from 5 to 311 microns. Design features that limit motion may be advantageous in limiting the amount of polyethylene debris.

Acetabulum↗
PubMed1998

A smoking cessation programme conducted through dental practices in the UK.

OBJECTIVES: To assess the feasibility of using primary care dentists and the dental team providing smoking cessation advice in practice. DESIGN: A prospective study to examine the success of a smoking cessation programme. SETTING: 54 primary care dental practices in the UK. METHOD: Training and educational materials were supplied to members of the dental team and to potential recruits smoking 10 or more cigarettes a day. Recruitment was over 6 months and subjects were followed up for 9 months. In addition to dentists' counselling, nicotine patches were made available, on request, at cost price. Salivary cotinine assay was used for validation of smoking levels at initial counselling and 9 months after recruitment. RESULTS: 54 practices were enrolled but only 22 recruited patients. Records of 154 eligible patients were evaluated. Compliance to attend follow up clinics was poor--only 74 reported at 9 months. Among them 17 (11%) were successful in giving-up tobacco for 9 months as validated by patient histories and salivary cotinine assay. A large variation performance of the dental practices was noted. CONCLUSIONS: Motivated dentists with staff support and access to information on smoking counselling are able to contribute to tobacco control measures in the community. The success of this programme closely parallels those reported in general medical practice settings. In view of the very considerable attrition rates found at all levels of the programme in the present study and the uneven performance of the participating practices the quit rate reported here may not accurately reflect what could be achieved in an individual primary care setting.

Adult↗
PubMed1998

Effect of antidepressant drugs on dopamine D1 and D2 receptor expression and dopamine release in the nucleus accumbens of the rat.

This study examined the effect of repeated treatment with the antidepressant drugs, fluoxetine, desipramine and tranylcypromine, on dopamine receptor expression (mRNA and binding site density) in sub-regions of the nucleus accumbens and striatum of the rat. The effect of these treatments on extracellular levels of dopamine in the nucleus accumbens was also measured. Experiments using in situ hybridisation showed that the antidepressants caused a region-specific increase in D2 mRNA, this effect being most prominent in the nucleus accumbens shell. In contrast, none of the treatments increased D1 mRNA in any of the regions examined. Measurement of D2-like binding by receptor autoradiography, using the ligand [3H]YM-09151-2, revealed that both fluoxetine and desipramine increased D2-like binding in the nucleus accumbens shell; fluoxetine had a similar effect in the nucleus accumbens core. Tranylcypromine, however, had no effect on D2-like binding in the nucleus accumbens but decreased binding in the striatum. In micro-dialysis experiments, our data showed that levels of extracellular dopamine in the nucleus accumbens were not altered in rats treated with either fluoxetine or desipramine, but increased by tranylcypromine. From our findings, we propose that the antidepressant drugs tested enhance dopamine function in the nucleus accumbens through either increased expression of post-synaptic D2 receptors (fluoxetine and desipramine) or increased dopamine release (tranylcypromine).

Animals↗
PubMed1998

Allograft heart valve viability and valve-processing variables.

BACKGROUND: The impact of allograft valve viability on valve durability remains controversial. Analyses of our clinical results have demonstrated the superiority of the cryopreserved valve viable at the time of implantation over the 4 degrees C stored valve nonviable at the time of implantation. In this study, we quantitatively assessed the effects on viability of current and past valve-processing protocols at The Prince Charles Hospital. METHODS: The viability of pulmonary valves was quantitatively analyzed by thin-layer autoradiography to assess the effects of donor type, antibiotics, and valve storage. RESULTS: Control valve segments obtained from beating-heart donor valves had a higher initial viability (0.92+/-0.02) than nonbeating-heart donor valves (0.66+/-0.03). Cryopreservation after low-dose antibiotic sterilization significantly reduced viability to 50% to 60% of the control, and in the presence of amphotericin B, viability dropped further to 10% to 36% of the control. After 7 days' storage at 4 degrees C, viability was reduced to 2% of control and to 0% viability after 21 days. CONCLUSIONS: For maximal preimplantation viability, valves should be procured as soon as possible after cessation of heart beat and should be cryopreserved if they are not to be clinically implanted within 1 to 2 days. Amphotericin B should not be used in conjunction with cryopreservation if viability is to be maximized.

Amphotericin B↗
PubMed1998

Average 12-year outcome of a chrome-cobalt, beaded, bony ingrowth acetabular component.

Seventy-two hips (67 patients) were reconstructed with the Acetabular Reconstruction Component (ARC, Howmedica, Rutherford, NJ), a chrome-cobalt component with sintered ingrowth beads and peripheral flanges for screw fixation. All the materials used in the ARC (metal, porous layer, and polyethylene) are identical to those used in the Porous Coated Anatomic (PCA) acetabular component (Howmedica), but the design is different. To determine the importance of design features alone, clinical results obtained with the 2 different designs made of identical materials were compared. The average follow-up period for patients with the ARC was 12 years (range, 10-13.3 years). Seven patients (7 hips) with the ARC died prior to the minimum 10-year follow-up period, none having undergone revision procedures. Overall, 3 acetabular components (4%) in 3 patients were revised, at an average of 8.5 years (range, 7.6-9.3 years) from the index operation. The reasons for revision were aseptic loosening, third-body polyethylene wear observed during a revision for femoral lysis, and acetabular component malposition and recurrent dislocation. The total incidence of acetabular aseptic loosening was 4% (3 of 72 hips). Pelvic osteolysis occurred in 3 cases (4%). In contrast, the incidence of acetabular revision of the PCA acetabular component at follow-up periods of 2-10 years is reported to be as high as 11% (range, 3-11%). Rates of aseptic loosening are as high as 30% (range, 3-30%) at substantially shorter follow-up periods, and the incidence of pelvic osteolysis associated with the PCA component is also as high as 30% (range, 5-30%). These differences may reflect differences in design between the 2 acetabular components, as the materials used were identical. In this, the longest reported average follow-up study of a successful cementless acetabular component, the aseptic loosening rate of 4% contrasts with the 42% rate at similar follow-up duration for cemented acetabular components placed by the same surgeon in patients of similar age.

Acetabulum↗
PubMed1998

Simultaneous detection of chromosomes X, Y, 13, 18, and 21 by fluorescence in situ hybridization in blastomeres obtained from preimplantation embryos.

PURPOSE: Simultaneous fluorescence in situ hybridization (FISH) was used in a preimplantation genetic diagnosis program to determine which embryos were normal for chromosomes X, Y, 13, 18, and 21. METHODS: Single blastomeres were disrupted and attached to glass slides using acetic acid and ethanol. Using a ratio mixture of chromosome enumeration DNA probes in combination with locus-specific identifier DNA probes, FISH was performed for the identification of chromosomes X, Y, 13, 18, and 21. RESULTS: Fourteen couples enrolled in IVF produced 134 embryos for biopsy. Blastomeres subjected to five-color FISH revealed that 22% of embryos were normal for chromosomes X, Y, 13, 18, and 21. In addition, 52% were abnormal and no results could be detected for 25%. Twelve couples underwent embryo transfer, two couples did not receive embryos due to lack of any normal embryos, and three couples became pregnant. CONCLUSIONS: The simultaneous detection of five-color FISH is a feasible method to detect aneuploidy in preimplantation embryos from women of advanced maternal age.

Adult↗
PubMed1998

Repeated administration of fluoxetine, desipramine and tranylcypromine increases dopamine D2-like but not D1-like receptor function in the rat.

We tested the effect of repeated treatment (twice daily for 14 days) of rats with the antidepressant drugs fluoxetine, desipramine and tranylcypromine, on the behavioural response to the non-selective dopamine (DA) receptor agonist, apomorphine, the D1-like receptor agonists, SKF 38393 and SKF 81297 and the D2-like receptor agonists, RU 24213 and quinpirole. Agonist-induced behaviour was monitored by automated activity meters and direct observation using a checklist scoring method. Fluoxetine, desipramine and tranylcypromine enhanced (albeit to a varying degree) the behavioural responses to apomorphine (0.75 mg/kg, s.c.), quinpirole (0.25 mg/kg, s.c.) and RU 24213 (0.75 mg/kg, s.c.). In contrast, fluoxetine, desipramine and tranylcypromine did not increase the behavioural responses to SKF 38393 (7.5 mg/kg, s.c.) and SKF 81297 (0.5 mg/kg, s.c.). Finally, fluoxetine, despiramine and tranylcypromine did not modify the behavioural responses to the concomitant administration of SKF 38393 (7.5 mg/kg, s.c.) and quinpirole (0.25 mg/kg, s.c.). Our data suggest that repeated administration of fluoxetine, desipramine and tranylcypromine increases central DA D2-like but not D1-like receptor function.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

Expression of heparan sulfate proteoglycan (perlecan) in the mouse blastocyst is regulated during normal and delayed implantation.

Previous studies have shown that expression of the heparan sulfate proteoglycan, perlecan, on the external trophectodermal cell surfaces of mouse blastocysts increases during acquisition of attachment competence. However, it is not clear if this change in perlecan protein expression also is reflected at the level of perlecan mRNA expression. In the present investigation, the spatial and temporal patterns of perlecan mRNA expression in the mouse embryo during the periimplantation period were examined by in situ hybridization and reverse transcriptase-polymerase chain reaction. In addition, a delayed implantation model was used to determine the expression of perlecan mRNA and protein in dormant and estrogen-activated hatched blastocysts. The results demonstrate that perlecan mRNA expression is low in morulae, but increases in Day 4 blastocysts, attaining maximal expression in Day 4.5 attachment-competent blastocysts. In contrast, perlecan mRNA is detected in both the dormant and estrogen-activated delayed blastocysts; however, within 12 hr of blastocyst activation by estrogen, both perlecan protein and heparan sulfate chain expression markedly increase. Taken together, these results suggest that during normal development perlecan mRNA expression increases with the acquisition of attachment competence. Moreover, perlecan protein expression also is attenuated during delayed implantation and appears to increase in response to nidatory estrogen, perhaps via the increased translation of preexisting perlecan mRNA.

Animals↗
PubMed1997

Evidence that the enhancement of dopamine function by repeated electroconvulsive shock requires concomitant activation of D1-like and D2-like dopamine receptors.

In this study, the behavioural response to dopamine D1-like receptor agonists (SKF 38393, SKF 81297 and SKF 77434) and D2-like receptor agonists (quinpirole and RU 24213), administered alone and in combination to rats treated repeatedly with electroconvulsive shock (five ECS over 10 days) or sham, was tested. Agonist-induced behaviour was monitored by automated activity meters and direct observation using a checklist scoring method. Repeated ECS (compared to sham controls) had no significant effect on the behavioural response to SKF 38393 (7.5 mg/kg s.c.), SKF 81297 (0.2 mg/kg s.c.), SKF 77434 (0.1 mg/kg s.c.), quinpirole (0.1 and 0.25 mg/kg s.c.) or RU 24213 (0.3 mg/kg s.c.), when administered alone. In contrast, repeated ECS markedly increased locomotion (activity counts and scores) induced by the non-selective dopamine agonist apomorphine (0.5 mg/kg SC) and by co-administration of a D1-like agonist plus a D2-like agonist [SKF 38393 (7.5 mg/kg s.c.) plus quinpirole (0.25 mg/kg s.c.), SKF 81297 (0.2 mg/kg s.c.) plus quinpirole (0.1 mg/kg s.c), and SKF 77434 (0.1 mg/kg s.c.) plus RU 24213 (0.3 mg/kg s.c.)]. This ECS-induced enhancement of dopamine-mediated behaviour was observed for up to 3 weeks after cessation of ECS treatment. In addition, ECS also enhanced the locomotor response to intra-accumbens SKF 38393 plus quinpirole (0.4 and 1.0 microgram/side, respectively). These results provide evidence that the enhancement of dopamine function by repeated ECS requires concomitant stimulation of both D1-like and D2-like receptors, and that this effect is long-lasting.

Animals↗
PubMed1997

Enhancement of dopamine-mediated behaviour by the NMDA antagonists MK-801 and CPP: similarities with repeated electroconvulsive shock.

The behavioural effect of dopamine D1-like receptor agonists (SKF 38393, SKF 81297) and a D2-like receptor agonist (quinpirole), administered alone and in combination, was tested in rats pretreated with a single injection of an NMDA antagonist (MK-801, CPP) or vehicle. Agonist-induced behaviour was monitored by automated activity meters and direct observation using a checklist scoring method. Pretreatment with MK-801 (0.05 mg/kg, SC, 30 min) had no significant effect (compared to controls) on the behavioural response to SKF 38393 (7.5 mg/kg SC), SKF 81297 (0.2 mg/kg SC) or quinpirole (0.1 and 0.25 mg/kg SC) administered alone. In contrast, MK-801 markedly increased locomotion (activity counts and scores) induced by co-administration of a D1-like plus a D2-like agonist [SKF 38393 (7.5 mg/kg) plus quinpirole (0.25 mg/kg), SKF 81297 (0.2 mg/kg) plus quinpirole (0.1 mg/kg)]. The behavioural response to the non-selective dopamine agonist apomorphine (0.5 mg/kg SC) was also enhanced by MK-801. Pretreatment with CPP (0.1 mg/kg SC, 30 min) also significantly increased the locomotor response to co-administration of SKF 38393 plus quinpirole administered alone, but had no effect on the behavioural response to separate injection of these agonists. MK-801 (0.05 mg/kg SC, 30 min) also enhanced the behavioural response to bilateral injection into the nucleus accumbens of SKF 38393 plus quinpirole (1.0 plus 0.4 microgram/side, respectively). These data suggest that in the intact rat, the enhancement of dopamine-mediated behaviour by either MK-801 or CPP requires concomitant stimulation of D1-like and D2-like receptors, possible located within the nucleus accumbens. The effect of these NMDA antagonists on dopamine function is similar to that of repeated electroconvulsive shock (ECS), indicating that one of the actions of ECS may be to reduce NMDA receptor function.

Animals↗