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Biomedical subjects

L Marshall

Publications and source records attributed to L Marshall.

At least 55 records · Page 3Linked to original sources

Research initiatives at the University of Toronto Environmental Hypersensitivity Research Unit.

The Environmental Hypersensitivity Research Unit at the University of Toronto is following a research strategy to develop and evaluate diagnostic methods for environmental hypersensitivity. These methods will be used to identify cases for inclusion in studies of disease etiology and therapy. The Research Unit has actively sought consultation and collaboration with researchers at the University of Toronto, clinicians from a variety of specialties, and patients. It is hoped that such a multidisciplinary approach will lead to the generation and testing of innovative hypothesis with rigorous methodology and, ultimately, to increased understanding of the complex conditions known as environmental hypersensitivity.

Canada↗

Effect of step size on clinical and adaptive 2IFC procedures in quiet and in a noise background.

Audibility thresholds for a 1000-Hz sinusoid were measured with a standard clinical (CLIN) procedure and a two-interval, forced-choice (2IFC) adaptive procedure bracketing 79% correct. Both used 2- and 5-dB step sizes in quiet and in a continuous, broadband noise background. Clinical thresholds were from 2 to 4 dB higher than 2IFC thresholds, depending on the condition. Step size had a larger effect on the CLIN thresholds than the 2IFC thresholds. For the CLIN procedure, thresholds with a 2-dB step size were 1.4 dB lower than with a 5-dB step size. For the 2IFC procedure, thresholds with a 2-dB step size were 0.8 dB higher than with a 5-dB step size. Reliability, as measured by the intrasubject standard deviation, was better for the 2IFC than for the CLIN procedure and better in noise than in quiet. Reliability was unaffected by step size. Adding extra trials to the 2IFC adaptive track decreased the variability across threshold estimates, but more for the noise background than the quiet background. The efficiency of the 2IFC procedure was fairly constant across track length in noise, but decreased for longer track lengths in quiet. In both quiet and noise backgrounds, CLIN procedures were much more efficient than 2IFC procedures.

Adult↗

Slow potential shifts at sleep--wake transitions and shifts between NREM and REM sleep.

Scalp-recorded direct current (DC) potentials and their topographical distribution (F3, F4, C3, C4 and Pz) were investigated at the transition from wakefulness to sleep, and during NREM-REM sleep and REM-NREM sleep transitions in 11 healthy men during normal sleep. Changes in endexpiratory CO2 partial pressure (ETCO2), scalp temperature and polysomnographic data were simultaneously measured. The transition to sleep was associated with a negative potential shift reaching significance bilaterally at frontal and central sites 5 to 10 minutes after sleep onset (p < 0.05). Largest shifts were found at frontal locations 10 to 15 minutes after sleep onset averaging (mean +/- SEM) -512 +/- 103 mu V. Negative DC potential shifts also occurred at the transitions from NREM to REM sleep and from REM to NREM sleep, but were, however, less pronounced. The negative DC shift at NREM-REM sleep transitions preceded the REM sleep onset (assessed conventionally by polysomnographic criteria) by about 1.5 minutes. Changes in temperature, ETCO2 and eye movements were ruled out as factors significantly contributing to the generation of these shifts. Assuming a neuronal origin of the DC potential, the negative shifts at the wake--sleep transition and between NREM and REM sleep suggest a temporary phase of increased cortical excitability.

Adult↗

Reliability of transient-evoked otoacoustic emissions.

OBJECTIVE: This investigation addressed four factors affecting transient-evoked otoacoustic emission (TEOAE) reliability: 1) The effect of evoking-stimulus level, 2) the effect of analyzing bandwidth, 3) the effect of slight-mild hearing loss, and 4) the effect of variability in the stimulus spectrum. DESIGN: TEOAEs at 80, 74, 68, and 62 dB pSPL evoking-stimulus levels were measured in 25 ears spanning a range of hearing levels from normal to mild hearing loss for a minimum of 10 test sessions. Reliability was assessed for 1/6-, 1/3-, 1/2-, and 1-octave analyzing bandwidths. RESULTS: Evoking-stimulus level, hearing loss, and center frequency did not significantly affect reliability. With decreasing analyzing bandwidth, reliability decreased. Intrasubject test-retest standard deviations were 1.2 dB for a broadband analyzing bandwidth and 1.4, 1.5, 1.6, and 1.8 dB for 1-, 1/2-, 1/3-, and 1/6-octave analyzing bandwidths, respectively. Stimulus variability within narrower bandwidths was of sufficient magnitude to influence test-retest reliability, and attempts to correct for the variations in stimulus spectrum were unsuccessful. Slopes of the input-output functions differed across frequencies, with shallower slopes at higher frequencies. CONCLUSIONS: In general, TEOAE amplitude is highly reliable. For those individuals in this study who were more variable, the variability was at low frequencies or across the entire frequency spectrum. For clinical applications, the choice of analyzing bandwidth should be based on consideration of both frequency specificity (where narrow analyzing bandwidths are optimal) and reliability (where wide analyzing bandwidths are optimal).

Acoustic Impedance Tests↗

Efficacy and potency of antivenoms in neutralizing the procoagulant effects of Australian snake venoms in dog and human plasma.

The efficacy and potency of Commonwealth Serum Laboratories (CSL) snake antivenoms in neutralizing the procoagulant action of Australian snake venoms was studied in vitro. The procoagulant action of venoms from Tiger, Brown and Taipan Snakes were measured in pooled canine or pooled human plasma. Mixtures of the venoms and their appropriate antivenoms, ranging from 0.1 to 15 times the recommended neutralizing dose of antivenom were then added to pooled canine or pooled human plasma and the efficacy and potency of the antivenoms in preventing the procoagulant action was measured. Neutralization was achieved by the addition of the appropriate antivenom in concentrations of 0.5 (Taipan), 10 (Tiger), 10 (Gwardar), 15 (Dugite) and an estimated 20 (Common Brown) times the dose expected. Similar results were obtained in canine and human plasma. The potency of Tiger and especially Brown Snake antivenom is substantially lower (10-20 times) than that predicted by CSL. These findings support an increase in the dose of antivenom to be used for the treatment of Tiger and especially Brown Snake envenomation complicated by coagulopathy. The in vitro canine model may be suitable for studying the procoagulant effects of Australian snake venoms.

Animals↗

Greater efficacy of episodic than continuous growth hormone-releasing hormone (GHRH) administration in promoting slow-wave sleep (SWS).

It has been suggested that growth hormone (GH)-releasing hormone (GHRH) stimulates the surge in GH and enhances slow-wave sleep (SWS), two phenomena that characterize the beginning of nocturnal sleep. However, in human studies the effects of systemic GHRH administration on sleep were not consistent. This may reflect the differential influence of administration procedures being episodic in one of the above studies, but either a continuous infusion or a single bolus in the others. The present study in healthy volunteers compared changes in nocturnal sleep following 200 micrograms GHRH administered iv either episodically (4 boluses of 50 micrograms each at 2200, 2300, 2400, and 0100 h) or as a continuous infusion (57 micrograms/h between 2130 and 0100 h). Time spent in stage 4 of SWS on nights of episodic GHRH administration significantly exceeded that on nights of continuous GHRH administration (P < 0.01). Compared with a placebo condition, episodic administration of GHRH enhanced SWS (P < 0.01) and rapid eye movement (REM) sleep (P < 0.05) and diminished time spent in wakefulness and sleep stage 1 (P < 0.05). Effects of continuous GHRH infusion on sleep generally remained insignificant compared with placebo. Plasma GH concentrations were enhanced during both conditions of GHRH administration (P < 0.01), with the increase following episodic administration slightly exceeding that during continuous infusion (P < 0.05). The results support a greater physiological efficacy of episodic GHRH stimulation in promoting sleep.

Adult↗

Effect of glycerol on intracellular virus survival: implications for the clinical use of glycerol-preserved cadaver skin.

Glycerol has long been used for the preservation of skin allografts. The antimicrobial activity of glycerol has not been fully documented. This paper reports the results of an investigation of a model studying the effect of glycerol on the inactivation of intracellular viruses. Two viruses--herpes simplex type I (HSV-1) and poliovirus--were cultured within human dermal fibroblasts. These intracellular viruses were incubated with 50 per cent, 85 per cent and 98 per cent glycerol at 4 degrees C and 20 degrees C for 4 weeks. Each week, the cultures in glycerol and controls in fibroblast maintenance medium were assayed for virus infectivity by examining the ability of harvested viruses to infect further fibroblasts. At 4 degrees C, 85 per cent glycerol could not fully inactivate intracellular HSV-I or poliovirus even after 4 weeks; 98 per cent glycerol inactivated intracellular HSV-I (after 3 weeks) but could not fully inactivate intracellular poliovirus after 4 weeks. At 20 degrees C, 85 per cent glycerol inactivated intracellular HSV-I (within 1 week) but could not fully inactivate intracellular poliovirus after 4 weeks; 98 per cent glycerol inactivated intracellular HSV-I (within 1 week) and inactivated intracellular poliovirus (after 2 weeks). It is suggested that, on the basis of this study, glycerol can reduce intracellular virus infectivity but that its effects are very dependent on concentration, time and temperature such that we would recommend that allograft skin be exposed to 98 per cent glycerol for a minimum of at least 4 weeks at a minimum temperature of 20 degrees C before clinical use.

Cadaver↗

Scalp recorded direct current potential shifts associated with the transition to sleep in man.

Cortical direct current (DC) potentials are considered to reflect the state of cortical excitability which may change characteristically from wakefulness to sleep. The present experiments examined changes in the scalp recorded DC potential in 10 healthy humans at the transition from wakefulness to nocturnal sleep. For each subject, DC recordings obtained from Cz were evaluated for a 15 min pre-sleep onset interval and for a 20 min post-sleep onset interval, on 2 separate nights. Sleep stages were determined from standard sleep recordings. The transition from wakefulness to sleep coincided with a significant (P < 0.05) shift in the DC potential of negative polarity. Maximum negative potentials of (mean +/- S.E.M.) 500 +/- 130 microV (first night) and of 760 +/- 200 microV (second night) were reached at the end of the 20 min post-sleep onset interval. A number of possible technical and biological artifacts were controlled. It is reasonable to assume that the slow negative shift of the DC potential at the transition from wakefulness to sleep reflects increased cortical excitability. Whether the negative potential shift pertains during sleep, or is of transient nature and closely linked to the process of falling asleep, remains to be clarified.

Adolescent↗

The state of solid state.

This talk about future communications technology is all well and good, but what about the things we already have? What's going on with current technology? And if things are going to change, what will the transition be like? For an overview, JEMS talked to a group of EMS communications experts: Bruce Jackson, president of EMSAT: Advanced Technology for EMS, in the Los Angeles area; Mark Johnson, chief of Alaska's EMS Section, chairman of the National Association of State EMS Directors' Communications Committee; and Steven Buckley, communications and facilities planning manager of the Warner Group, a public safety communications consulting company in Woodland Hills, Calif. The following summarizes their views on current issues and their projections for the near future.

Diffusion of Innovation↗

Sickle cell disorders and chronic intravascular haemolysis are associated with low plasma heparin cofactor II.

Thrombotic events are known to be increased in patients with sickle cell syndromes and a variety of abnormalities of coagulation or endothelial function have been described, although the relevance of these findings either to the pathogenesis of vaso-occlusive phenomena or the risk of thrombosis are unclear. Heparin cofactor II (HCII) and antithrombin III are circulating inhibitors of thrombin and low plasma levels have been associated with an increased risk of thrombosis in otherwise healthy individuals. We describe for the first time abnormally low plasma levels of HCII in patients with sickle cell syndromes. 45 adult patients with sickle cell syndromes (31 SS, 10 SC, 4 S beta Thal) were compared with 61 age matched control patients for HCII in plasma. There was a highly significant reduction in HCII in SS patients irrespective of crisis or transfusion state 0.68 +/- 0.15 U/ml (mean +/- SD) compared with controls 1.00 +/- 0.19 U/ml (P < 0.001). HCII antigen was also significantly reduced (0.53 +/- 0.19 U/ml) compared with controls (1.02 +/- 0.23 U/ml, P < 0.0001). By contrast there was no reduction in antithrombin III in this group. HCII (0.63 +/- 0.13 U/ml, P < 0.001) and HCII antigen (0.54 +/- 0.08 U/ml, P < 0.001) are also significantly reduced in SC patients HCII levels increased towards control values during sickle cell crises, in patients taking the contraceptive pill, or with regular blood transfusion; however, plasma HCII concentrations were not increased acutely by exchange transfusion. HCII was also decreased in thalassaemia intermedia and pyruvate kinase deficiency, suggesting that intravascular haemolysis may be the cause of reduced HCII levels.

Adult↗

Biochemical and clinical effects of aspartame in patients with chronic, stable alcoholic liver disease.

Aspartame is an artificial sweetener completely metabolized in the gut and absorbed as aspartate, phenylalanine, and methanol. Phenylalanine is thought to mediate or exacerbate hepatic encephalopathy, and an impaired liver may not be able to cope with the ammoniagenic properties of the amino acid constituents, or adequately metabolize methanol. Thus, we compared the clinical and biochemical effects of a single ingestion of aspartame (15 mg/kg) to skim milk (phenylalanine content equimolar to aspartame) and placebo in patients with chronic, alcoholic liver disease in a randomized, crossover study. Aspartame produced an elevation of plasma phenylalanine significantly greater than milk and placebo (Cmax 14.55 +/- 7.38, 10.95 +/- 4.95, 8.84 +/- 4.55 mumol/dl, respectively; p < 0.01). However, quantified encephalopathic changes were observed only with milk (p < 0.05). Plasma aspartate, methanol, formate, and ammonia levels remained unchanged after all treatments. The lack of clinical derangements in encephalopathic indices, methanol accumulation, or biochemical changes in liver status suggests that a single large dose of aspartame (representing 5 times the average daily intake of adults) may be used safely by patients with chronic, stable liver disease.

Amino Acids↗