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Biomedical subjects

J D Miller

Publications and source records attributed to J D Miller.

At least 217 records · Page 12Linked to original sources
PubMed1991

Method for the location of burst-onset spectra in the auditory-perceptual space: a study of place of articulation in voiceless stop consonants.

A method for distinguishing burst onsets of voiceless stop consonants in terms of place of articulation is described. Four speakers produced the voiceless stops in word-initial position in six vowel contexts. A metric was devised to extract the characteristic burst-friction components at burst onset. The burst-friction components, derived from the metric as sensory formants, were then transformed into log frequency ratios and plotted as points in an auditory-perceptual space (APS). In the APS, each place of articulation was seen to be associated with a distinct region, or target zone. The metric was then applied to a test set of words with voiceless stops preceding ten different vowel contexts as produced by eight new speakers. The present method of analyzing voiceless stops in English enabled us to distinguish place of articulation in these new stimuli with 70% accuracy.

Adult↗
PubMed1991

Suppression of carbamazepine-induced rash with prednisone.

We report our experience with 20 patients who developed a rash shortly after the introduction of carbamazepine and were treated with prednisone and an antihistamine. Sixteen patients were successfully continued on carbamazepine while 4 had to discontinue the drug.

Adult↗
PubMed1991

Long-term outcome following anterior cerebral artery ligation for ruptured anterior communicating artery aneurysms.

The long-term prognosis (15 years) was determined for 17 patients who had undergone anterior cerebral artery (ACA) ligation as the sole treatment for an anterior communicating artery aneurysm. The number of early and late rebleeds was lower than expected from previously ruptured aneurysms. Late ischemia was not a major complication while late postoperative epilepsy occurred in 19% of survivors. In a review of previously published series, ACA ligation appears to have significantly reduced the rates of both early and late rebleeding. This study helps to define the late results of "conservative" operations for ruptured aneurysms.

Cerebral Angiography↗
PubMed1991

Ischemic neuronal damage after acute subdural hematoma in the rat: effects of pretreatment with a glutamate antagonist.

The ability of a competitive N-methyl-D-aspartate (NMDA) receptor antagonist (D-CPP-ene) to reduce irreversible brain damage has been examined in a rodent model of acute subdural hematoma. Acute subdural hematoma was produced by the slow injection of 400 microliters homologous blood into the subdural space overlying the parietal cortex in halothane-anesthetized rats. Brain damage was assessed histologically in sections at multiple coronal planes in animals sacrificed 4 hours after induction of the subdural hematoma. Pretreatment with D-CPP-ene (15 mg/kg) significantly reduced the volume of ischemic brain damage produced by the subdural hematoma from 62 +/- 8 cu mm (mean +/- standard error of the mean) in vehicle-treated control rats to 29 +/- 7 cu mm in drug-treated animals. These data demonstrate the anti-ischemic efficacy of NMDA antagonists in an animal model of intracranial hemorrhage in which intracranial pressure is elevated, and suggest that excitotoxic mechanisms (which are susceptible to antagonism by D-CPP-ene) may play a role in the ischemic brain damage which is observed in patients who die after acute subdural hematoma.

Animals↗
PubMed1991

Dopamine D2 mechanisms in canine narcolepsy.

Narcolepsy is a sleep disorder characterized by abnormal manifestations of rapid-eye-movement (REM) sleep and excessive daytime sleepiness. Using a canine model of the disease, we found that central D2 antagonists suppressed cataplexy, a form of REM-sleep atonia occurring in narcolepsy, whereas this symptom was aggravated by D2 agonists. The effect on cataplexy was stereospecific for the S(-) enantiomer of sulpiride (a D2 antagonist) and the R(+) enantiomer of 3-PPP (a D2 agonist). There was also a significant correlation between the in vivo pharmacological potency and in vitro drug affinity for D2 receptors (but not for D1 and alpha 2 receptors) among the seven central D2 antagonists tested. Selective D1 compounds were also tested; however, the results were inconsistent because both antagonists and agonists generally suppressed cataplexy. Our current results demonstrate that central D2-type receptors are critically involved in the control of cataplexy and REM sleep. Furthermore, the finding that small doses of D2 antagonists suppressed cataplexy and induced behavioral excitation, while small doses of D2 agonists aggravated cataplexy and induced sedation, suggests that this effect is mediated presynaptically. However, considering the fact that selective dopamine reuptake inhibitors did not modify cataplexy and that our previous pharmacological results demonstrated a preferential involvement of the noradrenergic system in the control of cataplexy, we believe that the effect of D2 compounds on cataplexy is mediated secondarily via the noradrenergic systems.

Animals↗
PubMed1991

Plasma atrial natriuretic factor concentrations in a canine model of right heart pressure overload.

Two studies were carried out in order to evaluate the plasma atrial natriuretic factor (ANF) concentrations, as well as hemodynamic and renal profiles in a chronic canine model of right heart pressure overload induced by pulmonary artery (PA) banding. In study I (n = 6), the animals were submitted to a gradual increase in pressure to clarify whether an increase in pressure or atrial distension was the main stimulus to ANF secretion. In study II (n = 6), right heart pressure overload was produced more rapidly, resulting in fluid retention and weight gain, thereby completing the model of right heart failure, and allowing an evaluation of the mechanisms involved in ANF resistance. In study I there were significant increases in right atrial pressure over baseline at 20 weeks, ANF levels at 24 weeks and right atrial area at 28 weeks following PA banding. In study II right heart pressures and ANF levels were higher than baseline at 12 weeks (p less than 0.0001), and fluid retention developed between 12-24 weeks in all dogs. The results suggest that increased right heart pressure, rather than atrial size, is a primary stimulus to ANF secretion in chronic right heart pressure overload. Despite the increases in right atrial pressure, clinical fluid retention occurred only with elevations of renin and aldosterone.

Aldosterone↗
PubMed1991

Treatment of leiomyomata uteri with leuprolide acetate depot: a double-blind, placebo-controlled, multicenter study. The Leuprolide Study Group.

The purpose of this study was to evaluate efficacy and safety parameters in women with leiomyomata uteri treated with the GnRH agonist leuprolide acetate depot, 3.75 mg intramuscularly every 4 weeks for 24 weeks. One hundred twenty-eight patients were enrolled in a randomized, double-blind, placebo-controlled multicenter study involving 13 investigative centers. Mean uterine volume decreased by 36% at 12 weeks and 45% at 24 weeks of leuprolide therapy. Patients treated with placebo had increased in mean uterine volume of 16% at 12 weeks and 5% at 24 weeks. Seventy-seven percent of leuprolide-treated patients had a more than 25% reduction in uterine volume, compared with 9% of placebo-treated controls. Mean uterine volume returned to pre-treatment size 24 weeks after cessation of leuprolide treatment. The majority of patients had resolution or improvement of their fibroid-related symptoms after 24 weeks of leuprolide treatment. Of 38 leuprolide-treated patients presenting with menorrhagia, 37 (97%) had resolution of this symptom at the time of the final visit. Although 95% of women treated with leuprolide acetate experienced some side effects related to hypoestrogenism, only five patients (8%) terminated treatment prematurely. We conclude that leuprolide acetate depot treatment of leiomyomata uteri is safe and causes significant but temporary reductions in uterine size and fibroid-related symptoms.

Adult↗
PubMed1990

Excretion of epidermal growth factor (EGF) in diabetes.

Excretion of epidermal growth factor (EGF) is decreased in renal failure. We assayed it in diabetes mellitus in an attempt to relate it to clinical parameters, esp. those of diabetic nephropathy. EGF excretion declined with age but in all age groups of diabetic patients was below the first percentile for controls. In 26 control and 34 prepubertal diabetic children excretion was correspondingly 1126 +/- 442 and 932 +/- 489 pmol/mmol creatinine (P = 0.087); in 26 control and 42 diabetic adolescents below age 18, 778 +/- 222 and 676 +/- 335 (P = 0.023) and in 81 control and 83 diabetic adults, 371 +/- 153 and 235 +/- 140 (P less than 0.0001). Decreased excretion of EGF was seen in some patients without any diabetic complications. Excretion of EGF was independently and inversely correlated with age and duration of diabetes but not with type of diabetes, treatment, body built, C-peptide, plasma glucose, glycohemoglobin or retinopathy. A positive correlation was seen with creatinine clearance and a negative correlation, with albuminuria, but the strongest and the only independent correlation found by stepwise multiple variable selection was with serum creatinine (r -0.711, P less than 0.0001). EGF excretion was not elevated in patients with hyperfiltration. We conclude that EGF excretion is abnormal in many patients with diabetes and that this abnormality reflects a kidney function different from glomerular filtration or glomerular permeability.

Adolescent↗
PubMed1990

A serotonin agonist phase-shifts the circadian clock in the suprachiasmatic nuclei in vitro.

The mammalian circadian pacemaker in the suprachiasmatic nuclei (SCN) receives a large serotonergic (5-HTergic) projection from the raphe nuclei. Whether the SCN pacemaker can be modulated by this afferent projection is a question of considerable theoretical and practical interest. In this study we investigated whether the 5-HT agonist, quipazine, can reset the phase of the SCN clock when it is isolated in vitro. Our results show that 1 h treatments with quipazine induce robust phase shifts in vitro, and that this effect depends upon the circadian time of treatment. We further show that the ability of quipazine to induce phase shifts is dose-dependent. These results suggest that the SCN circadian pacemaker is sensitive to 5-HTergic stimulation, and therefore that the 5-HTergic projection to the SCN may play a role in modulating the phase of the SCN clock in the intact animal.

Animals↗
PubMed1990

The response of suprachiasmatic neurons of the rat hypothalamus to photic and serotonergic stimulation.

Single-unit activity of the rat suprachiasmatic nucleus and surrounding regions was recorded in vivo. Photically responsive neurons were typically inhibited by low intravenous doses of the serotonin (5-HT) agonist quipazine. The 5-HT antagonist, metergoline, administered in a low intravenous dose, reversed the effects of quipazine. The subsequent response to photic stimulation was essentially identical to the initial photic response. Thus the photic response of neurons in the suprachiasmatic nucleus (SCN) and adjacent regions is relatively uninfluenced by 5-HT blockade.

Action Potentials↗
PubMed1990

Effect of calcitonin-gene-related peptide on postoperative neurological deficits after subarachnoid haemorrhage.

An infusion of calcitonin-gene-related peptide (CGRP) at progressively increased concentrations was given to 15 patients with neurological deficits after intracranial aneurysm surgery for subarachnoid haemorrhage. In 9 of the patients the deficits, quantified by a modified Glasgow coma scale, improved with no adverse effects; after a placebo infusion only 2 of the 15 patients showed improvement. If CGRP can reverse cerebral ischaemia after early intracranial aneurysm surgery, its use may improve the safety of such early surgery, remove the need for late surgery with its increased risk of death from rebleeding, and reduce overall morbidity and mortality of aneurysmal subarachnoid haemorrhage.

Adult↗
PubMed1990

CNS monoamines and their metabolites in canine narcolepsy: a replication study.

In two separate studies a significantly greater concentration of DA (dopamine) and its metabolite, DOPAC (3,4-dihydroxyphenylacetic acid), was observed in the amygdala of narcoleptic canines. DOPAC was also significantly elevated in the reticularis parvicellularis, whereas NE (norepinephrine) was significantly elevated in the reticularis oralis, but depressed in the preoptic hypothalamus. No changes were observed in concentrations of serotonin or its metabolite, 5-HIAA (5-hydroxyindoleauric acid) in any region in the narcoleptic canine brain. Results of the two studies were similar, except that previously observed differences between narcoleptic and control canines in DOPAC levels in the caudate and reticularis oralis failed to replicate. Thus, steady state measures of neurotransmitter/metabolite tissue concentrations suggest region-specific alterations in DA and NE metabolism, rather than a global deficit in catecholamine neurotransmission in canine narcolepsy.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Secondary insults during intrahospital transport of head-injured patients.

Secondary pathophysiological insults occurring after injury have been prospectively assessed in 50 head-injured patients who required intrahospital transfer. 35 patients were transported from the intensive care unit (ICU) and 15 from the accident and emergency department. Physiological variables were recorded every minute in the four hours before transfer (ICU group only), during the move, and for four hours afterwards. Pretransfer insults were predictive of further insults during and after transport. There was significant correlation between increased frequency of insults post-transfer (compared with pre-transfer) and high injury severity score. A greater proportion of the patients transported from the emergency department had secondary injuries post-transfer. Adequate resuscitation before moving the patient, especially in patients with multiple injury, is important.

Adolescent↗
PubMed1990

Automated time-averaged analysis of craniospinal compliance (short pulse response).

We have developed an automated method [Short Pulse Response (SPR)] of measuring craniospinal compliance using an electronic square wave pressure generator to produce a small (0.05 ml) and reproducible transient volume increase in the CSF space (pulse duration 100 msec). In experimental models of intracranial hypertension, arterial hypertension, arterial hypotension and arterial hypercarbia in cats, the new method accurately followed physiological changes in compliance when compared to the manual volume-pressure injection method. The VPR overestimated compliance compared to the new SPR method (by 20% to 162%, mean = 77%). The SPR method was less variable between sequential measurements with a coefficient of variation (CV) ranging from 0.6% to 9.6% (mean CV = 2.6%), compared with a CV ranging from 5.6% to 48% (mean CV = 17%) for the VPR method. Repeated compliance measurements by the new method over a 12 hour period, produced no neuropathological evidence of either blood brain barrier breakdown or tissue damage resulting from the repeated volume injections.

Animals↗
PubMed1990

The contribution of secondary mediators to the etiology and pathophysiology of brain oedema: studies using a feline infusion oedema model.

Secondary mediator compounds are postulated to have a role in vasogenic oedematogenesis. They may also cause focal brain dysfunction due to their neuronal, axonal and glial modulating properties. Using the feline model of infusion brain oedema the effects of right frontal intracerebral infusion (200 microliters/hr for 3 hrs) of saline, bradykinin (10(-4) to 10(-6) M), arachidonic acid (10(-2) to 10(-3) M), 20% protein and four human glioma cyst fluids were evaluated. Somatosensory evoked potentials (SSEP), motor evoked potentials (MEPs), rCBF and rCBF CO2 reactivity (Hydrogen clearance). ICP, craniospinal compliance, local brain tissue water content (microgravimety), brain histology and BBB function (Evans Blue 2%) were measured. Brain water content increased locally from 69% to 79%, ICP increased (by mean 14 mmHg) and compliance decreased (mean 70%) and there were the histological features of brain oedema with all infusates. BBB opening occurred with Bradykinin (+), arachidonic acid (++), 20% protein ( ) and glioma cyst fluid (4+). Polymorphic and macrophage infiltrates were seen with all infusions but rCBF and MEPs remained normal. SSEPs changed with high dose bradykinin and some glioma cyst infusates whilst CBF CO2 reactivity was locally impaired by all infusates except saline and arachidonic acid. This study suggests that certain compounds in brain oedema fluid could mediate local brain dysfunction.

Animals↗
PubMed1990

Ischaemic brain damage associated with tissue hypermetabolism in acute subdural haematoma: reduction by a glutamate antagonist.

Ischaemia results in elevated extracellular glutamate concentrations, and drugs which act at the N-methyl-D-aspartate sub-type of glutamate receptor have been shown to decrease ischaemic brain damage. Because almost all patients who die after severe head injury demonstrate ischaemic brain damage, and acute subdural haematoma (ASDH) is one of the commonest complications of severe head injury, we have studied this condition in a rat model. Using double-label autoradiography, we have measured the effects of ASDH on cerebral glucose utilization and cerebral blood flow (RCBF). Following ASDH, increased glucose utilisation was observed in some cortical and hippocampal structures, without concomitant increases in blood flow. Directly below the ASDH, blood flow and glucose utilization were profoundly reduced. Pre-treatment with D-CPP-ene, a competitive NMDA antagonist, resulted in amelioration of hypermetabolism induced by the ASDH. The results suggest that NMDA antagonists may prevent ischaemic brain damage after ASDH by reducing hypermetabolism, induced by glutamatergic mechanisms.

Acute Disease↗