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Biomedical subjects

D Robertson

Publications and source records attributed to D Robertson.

At least 271 records · Page 15Linked to original sources
PubMed1991

Changes in cochlear sensitivity do not alter relative thresholds of different spontaneous rate categories of primary auditory nerve fibres.

The CF thresholds of three different spontaneous firing rate categories of single auditory nerve fibres were measured in guinea pigs with widely differing cochlear sensitivities. The CF thresholds for all fibres were compared to the CAP thresholds at the same frequencies. The relationship between single fibre CF threshold and CAP thresholds for the three different fibre categories remained unchanged despite the very wide range of absolute CAP thresholds. The widely ranging CAP thresholds in these animals were probably due to varying degrees of outer hair cell pathology and these data therefore support the notion that in normal animals, the origin of differences in threshold between fibres with different spontaneous rates, lies in the properties of the inner hair cells and/or their synapses with afferent dendrites.

Action Potentials↗
PubMed1991

Relationship between tone burst discharge pattern and spontaneous firing rate of auditory nerve fibres in the guinea pig.

A detailed investigation was carried out of the response of single auditory nerve fibres in the guinea pig to tone bursts. Comparisons were made between the shapes of peri-stimulus-time histograms (PSTHs) of low and high characteristic frequency (CF) fibres grouped according to their spontaneous firing rates (SR). Both low and high CF fibres of high spontaneous rate (greater than 18 spikes/s) exhibited marked rapid adaptation in their PSTH's which became most pronounced at high stimulus intensities. The ratio of onset-to-adapted firing estimated from PSTH data in these fibres increased monotonically as a function of adapted firing rate. The behaviour of fibres with the lowest spontaneous rates (less than 0.5 spikes/s) was markedly different, particularly in fibres from low CF regions. In general, these low-SR fibres showed slower adaptation than high-SR fibres, and a less pronounced onset peak. This was most striking in low CF fibres. Furthermore, the ratio of onset-to-adapted firing rate tended to decrease with increasing stimulus intensity in both low and high CF fibres with low spontaneous firing rates. Low-SR fibres also showed the highest maximum discharge rates to tone burst stimuli. Fibres with medium spontaneous rates between 0.5 and 18 spikes/s displayed intermediate characteristics in their PSTH's. Recent data in the chinchilla (Relkin and Doucet, 1991), suggest that these differences may arise in part from differences in inter-stimulus recovery processes in the different spontaneous rate groups.

Acoustic Stimulation↗
PubMed1991

Shapes of rate-versus-level functions of primary auditory nerve fibres: test of the basilar membrane mechanical hypothesis.

Rate-versus level functions (RI functions) for characteristic frequency (CF) stimulation were measured from primary auditory nerve fibres from different spontaneous rate categories in the guinea pig cochlea. Attention was focussed on those fibres that showed clear breakpoints in their RI functions (sloping-saturation fibres). A statistical curve fitting procedure to an empirical equation was used to provide a quantitative estimate of the breakpoint position in individual fibres. It was found that, within the limits of reliability of the curve fitting procedure, the breakpoint position was the same in fibres from the same CF regions in any given animal. This result is consistent with the notion that the breakpoint position is determined by global basilar membrane mechanics and not by processes private to each nerve fibre. However, a subgroup of fibres not easily classifiable as sloping-saturation, showed features of their RI functions suggesting that factors other than basilar membrane mechanics could lead to fibre-to-fibre differences in rate-versus-level behaviour.

Acoustic Stimulation↗
PubMed1991

Rate-versus-level functions of primary auditory nerve fibres: evidence for square law behaviour of all fibre categories in the guinea pig.

Detailed measurements of rate-versus-level (RI) functions close to threshold were made from single primary auditory nerve fibres in the guinea pig cochlea. For all fibres, a simple square law provided the best statistical fit to the data near threshold, regardless of spontaneous fibrin rate of the fibre. In no case was a better fit obtained with an exponent greater than 2. We conclude that a simple square law is an accurate description of the underlying synaptic drive to all primary auditory nerve fibres. For fibres with very low spontaneous firing rates the best square law fit near threshold frequently led to the formal mathematical estimate of a negative firing rate as the asymptotic value of the spontaneous firing rate. The 'negative spontaneous rate' of low spontaneous rate fibres derived from curve fitting can be conceptualized by postulating that for sound pressures well below threshold in these fibres the underlying synaptic drive lies below a threshold value at a site determining action potential generation.

Acoustic Stimulation↗
PubMed1991

Linkage analysis of the human dopamine beta-hydroxylase gene.

The human gene for dopamine beta-hydroxylase (D beta H) has been mapped to chromosome 9q34. Using polymerase chain reaction amplification of exon 11 of the D beta H gene followed by digestion of the reaction products with FnuDII (BstUI), we detected a low-frequency restriction fragment length polymorphism (RFLP). The CEPH panel of family DNAs was genotyped for this RFLP, enabling us to determine the linkage relationships between D beta H and four other loci previously mapped to human chromosome 9q. We obtained two-point recombination frequencies (theta) between D beta H and arginosuccinate synthetase (theta = 0, LOD = 7.37), the ABO blood group locus (theta = 0, LOD = 4.5), CRI-P111 (theta = 0, LOD = 2.1), and D9S31 (theta = .06, LOD = 2.81).

Base Sequence↗
PubMed1991

Direct vasodilator effect of hyperventilation-induced hypocarbia in autonomic failure patients.

Hyperventilation produces small decreases in blood pressure in normal subjects and larger decreases in patients with autonomic failure. The authors studied the mechanism for this observation by measuring mean arterial pressure (MAP) and arterial blood gas (ABG) changes in eight patients with severe primary autonomic failure after various maneuvers designed to alter PaCO2, PaO2, and pH. Maneuvers included voluntary hyperventilation, breathing a 5% CO2/95% O2 mixture, breathing 12% O2, breathing through a 1 meter tube to increase dead space, breathing 100% O2, and infusion of 120 mEq NaHCO3 over 30 minutes. All maneuvers led to expected changes in ABGs. Voluntary hyperventilation lowered MAP by 23 +/- 4 (p less than 0.01) mmHg but MAP was raised 11 +/- 3 and 7 +/- 1 mmHg by hyperventilation resulting from increasing breathing dead space or from breathing 5% CO2, respectively. Breathing 100% O2 or 12% O2 had no significant effect on MAP, and NaHCO3 infusion raised MAP by 8 +/- 4 (p less than 0.05) mmHg. With all maneuvers, change in MAP correlated with change in PaCO2 (r = 0.72, p less than 0.001) and change in pH (r = -0.57, p less than 0.01) but not with PaO2. Multiple regression analysis showed that only changes in PaCO2 predicted the change in MAP for all maneuvers. The authors conclude that a decrease in PaCO2 causes the observed decreases in MAP with hyperventilation. This most likely represents a direct peripheral vasodilator effect of hypocarbia rather than a reflex or centrally-mediated mechanism since our patient population is characterized by inadequate or absent autonomic cardiovascular reflex responses.

Autonomic Nervous System↗
PubMed1991

Sanfilippo syndrome type D in two adolescent sisters.

We report on two adolescent sisters with Sanfilippo syndrome type D with some clinical features different from other cases previously described. They are the oldest cases reported to date and provide new clues about the course of the disease. Enzymatic and immunological characterisation of the patients' fibroblasts indicated deficiency of N-acetylglucosamine-6-sulphate sulphatase (GlcNAc-6S sulphatase). However, Northern blot analysis showed apparently normal mRNA encoding GlcNAc-6S sulphatase. These findings suggest that abnormal translation or premature degradation may be responsible for the enzyme defect in these cases of Sanfilippo syndrome type D.

Adolescent↗
PubMed1991

Space infections of the head and neck--the "new" clinical picture.

A series of 12 neck space infections admitted to a military hospital in Germany in a 12 month period are presented. This represents an incidence of 1:1000 for the age group studied. The reappearance of the retropharyngeal abscess which has been rare since the widespread use of antibiotics, along with the generally high incidence of this group of infections, is probably a result of the more discriminating use of antibiotics in primary health care. The pitfalls in diagnosis and the preferred antibiotic cover are discussed.

Abscess↗
PubMed1991

Adenosine increases sympathetic nerve traffic in humans.

BACKGROUND: Adenosine is an effective hypotensive agent in experimental animals and in anesthetized patients, producing little if any evidence of reflex sympathetic activation. In contrast, adenosine increases systolic blood pressure and heart rate in conscious subjects. To determine whether this response is related to sympathetic activation, we studied the cardiovascular and respiratory effects of adenosine in normal subjects while measuring muscle sympathetic nerve traffic through direct recordings from a peroneal nerve. METHODS AND RESULTS: Adenosine (80 micrograms/kg/min i.v.) increased heart rate (+32 +/- 3 beats/min), systolic blood pressure (+10 +/- 2 mm Hg), and minute ventilation (+7 +/- 1 l/min). This was accompanied by a dose-dependent increase in muscle sympathetic nerve activity (from 198 +/- 52 to 451 +/- 92 units/min). Adenosine also produced a small, but consistent, decrease in diastolic blood pressure (-6 +/- 3 mm Hg). Adenosine produced a greater increase in sympathetic nerve traffic (145 +/- 32% above baseline) than did nitroprusside (65 +/- 16%) at doses that resulted in equivalent decreased in diastolic blood pressure. Arterial baroreceptor unloading, therefore, could not totally explain the increase in sympathetic traffic produced by adenosine. CONCLUSIONS: Given the constellation of findings of increased ventilation and sympathetic activity, we, therefore, propose that adenosine increases sympathetic tone by activating afferent nerves, including arterial chemoreceptors. Contrary to the known inhibitory actions of adenosine on central and peripheral efferent systems, this and other reports suggest that adenosine-induced activation of afferent nerves, leading to sympathetic activation, may be a more widespread phenomenon than previously recognized.

Adenosine↗
PubMed1991

Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation.

Dopamine beta-hydroxylase (DBH) deficiency is a genetic disorder in which affected patients cannot synthesize norepinephrine, epinephrine, and octopamine in either the central nervous system or the peripheral autonomic neurons. Dopamine acts as a false neurotransmitter in their noradrenergic neurons. Neonates with DBH deficiency have had episodic hypothermia, hypoglycemia, and hypotension, but survivors sometimes cope relatively well until late childhood when overwhelming orthostatic hypotension profoundly limits their activities. The hypotension may be so severe that clonic seizures supervene. Most currently recognized patients are young or middle-aged adults. The diagnosis is established by the observation of severe orthostatic hypotension in a patient whose plasma norepinephrine/dopamine ratio is much less than one.

Adult↗
PubMed1991

Cardiovascular excitatory effects of adenosine in the nucleus of the solitary tract.

Adenosine is an inhibitory neuromodulator in several brain regions. In the nucleus tractus solitarius (NTS), however, adenosine exerts excitatory cardiovascular effects. The purpose of the present study was to elucidate the involvement of other endogenous mechanisms that could contribute to the final hemodynamic response to adenosine in this nucleus. In normotensive Sprague-Dawley rats, intra-NTS microinjection of adenosine (2.3 nmol/60 nl) decreased blood pressure and heart rate. These effects were blocked by prior administration of the specific adenosine receptor antagonist 1,3-dipropyl-8-p-sulfophenylxanthine (0.92 nmol) and by the two glutamate receptor antagonists kynurenic acid and glutamic diethylester. The specificity of the adenosine-glutamate interaction in the NTS was demonstrated with adrenergic and angiotensin receptor antagonists that did not affect the adenosine response and by experiments with glutamate receptor antagonists that did not affect nicotine actions in the NTS. Furthermore, an increase in glutamate levels was demonstrated during perfusion of adenosine through a microdialysis probe in the NTS of anesthetized rabbits. These findings indicate that adenosine increases the release of glutamate in the NTS and, thus, are at variance with the concept of a "universal" inhibitory effect of adenosine in the central nervous system.

Adenosine↗
PubMed1991

[Mechanism of action of adenosine on intracellular calcium and platelet aggregation].

Adenosine inhibits platelet aggregation and elevates the levels of cytoplasmic Ca2+ induced by thrombin, 0.3 U/ml). When given at the maximal (100 microM) concentration, adenosine completely inhibits the aggregation, but only partially (by 55%) suppresses the growth of Ca2+, blocking both its entry and intracellular depot mobilization. Adenosine is likely to affect intracellular Ca2+, by activating adenylate cyclase, since 2',5'-didesoxyadenosine (1 mM) prevents the effect of adenosine, by inhibiting the enzyme, whereas the phosphodiesterase inhibitor papaverine (1 microM) potentiates its effect. When stimulated with adrenaline, 1 microM, adenosine and dibutyryl-cAMP are also able to inhibit platelet aggregation in the absence of cytoplasmic Ca2+ growth.

Adenosine↗
PubMed1990

Expression of the CD34 gene in vascular endothelial cells.

All seven of a set of CD34 monoclonal antibodies that recognize epitopes on an approximately 110 Kd glycoprotein on human hemopoietic progenitor cells also bind to vascular endothelium. Capillaries of most tissues are CD34 positive, as are umbilical artery and, to a lesser extent, vein, but the endothelium of most large vessels and the endothelium of placental sinuses are not. Angioblastoma cells and parafollicular mesenchymal cells in fetal skin are also CD34 positive, as are some stromal elements. An approximately 110 Kd protein can be identified by Western blot analysis with CD34 antibodies in detergent extracts of freshly isolated umbilical vessel endothelial cells, and CD34 mRNA is present in cultured umbilical vein cells as well as other tissues rich in vascular endothelium (breast, placenta). These data indicate that the binding of CD34 antibodies to vascular endothelium is to the CD34 gene product, and not to crossreactive epitopes. Despite the presence of CD34 mRNA in cultured, proliferating endothelial cells, the latter do not bind CD34 antibodies. In addition, CD34 antigen cannot be upregulated by growth factors. We conclude that under these conditions, CD34 protein is downregulated or processed into another form that is unreactive with CD34 antibodies. Electron microscopy of umbilical artery, breast, and kidney capillary vessels reveals that in all three sites, CD34 molecules are concentrated on membrane processes, many of which interdigitate between adjacent endothelial cells. However, well-established endothelial cell contacts with tight junctions are CD34 negative. CD34 may function as an adhesion molecule on both endothelial cells and hematopoietic progenitors.

Antibodies, Monoclonal↗
PubMed1990

Pressor effect of inhaled ergotamine in orthostatic hypotension.

Treatment of orthostatic hypotension due to autonomic failure frequently necessitates use of pressor agents. Because venous pooling contributes significantly to this disorder, the venoconstrictive properties of ergotamine offer theoretical advantages over pure arteriolar pressor agents. However, the low and erratic bioavailability of oral preparations has hindered the use of ergotamine. Accordingly, the efficacy of inhaled ergotamine tartrate (1 puff, 0.36 mg) was compared to placebo in 8 patients with severe autonomic failure. Blood pressure was monitored in the seated position with an automated device. Ergotamine produced significant increases in systolic (29 +/- 5 mm Hg, p less than 0.01 by analysis of variance) and diastolic (13 +/- 1 mm Hg, p less than 0.001) blood pressures compared to placebo (-9 +/- 5 and -2 +/- 3, respectively). Upright blood pressure 2 hours after administration was significantly greater with ergotamine (119 +/- 8/69 +/- 6 mm Hg) vs placebo (82 +/- 7/59 +/- 5 mm Hg, p less than 0.05). Motionless standing time, a measurement of functional capacity, also improved with ergotamine (200 +/- 58 vs 85 +/- 22 seconds). No side effects were noted, but patients with coronary or peripheral artery disease were excluded. Inhaled ergotamine may provide an effective and practical therapy for disabling orthostatic hypotension due to autonomic failure.

Administration, Inhalation↗