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Biomedical subjects

M E Drake

Publications and source records attributed to M E Drake.

At least 37 records · Page 2Linked to original sources
PubMed1994

Flunarizine for treatment of partial seizures: results of a concentration-controlled trial.

The National Institutes of Health sponsored a randomized, double-blind, multicenter, placebo-controlled trial of flunarizine (FNR) in epileptic patients receiving concomitant phenytoin (PHT) or carbamazepine (CBZ). Because of FNR's long half-life (up to 7 weeks), a parallel rather than crossover design was used. Each patient received an individualized loading dose and maintenance dosage targeted at a 60-ng/ml plasma FNR concentration. Of 93 patients randomized, 92 provided seizure data for the full 25-week treatment period; one placebo-treated patient dropped out for personal reasons. Fifty-four patients received CBZ only, nine received PHT only, and 30 received both CBZ and PHT. Eighty-seven patients had a history of complex partial seizures, and 60 had secondarily generalized seizures. Eight patients discontinued FNR prematurely, all because of adverse neurologic or psychiatric signs or symptoms; depression was the specific cause in three cases. Calculated maintenance dosages, based on single-dose pharmacokinetic profiles, ranged from 7 to 138 mg/day (mean, 40 mg/day). Plasma FNR concentrations generally exceeded the target, with the highest concentrations observed immediately after loading; excluding the first three treatment weeks and all concentrations after a FNR dosage change, the median plasma FNR concentration was 71.7 ng/ml. The percent reduction from baseline seizure rate was statistically greater (p = 0.002) in the FNR-treated group (mean, 24.4%) than in the placebo-treated group (mean, 5.7%).

Adolescent↗
PubMed1993

Intronic and 5' flanking sequences of the Drosophila beta 3 tubulin gene are essential to confer ecdysone responsiveness.

The expression of the beta 3 tubulin gene is regulated, at the transcriptional level, by the steroid hormone ecdysone, in Drosophila Kc cells. Using a transient expression assay, we show that 360 bp from the first intron of the beta 3 tubulin gene, associated with the 5' flanking sequences, are essential to confer ecdysone inducibility on a minimum promoter driving the chloramphenicol acetyl transferase (CAT) gene. The 5' flanking region contains ecdysone-independent cis-positive elements located in proximity to the promoter. Deletion analysis of the 360 bp intronic region reveals that a fragment of 57 bp is crucial for the ecdysone response of the beta 3 tubulin gene. This fragment contains 5'-TGA(A/C)C-3' motifs homologous to ecdysone responsive elements (EcRE) half sites. Band shift assays show that this 57-bp fragment is bound by three specific complexes. One of them appears to be involved in the level of the ecdysone response.

Animals↗
PubMed1993

Enhancer and silencer elements within the first intron mediate the transcriptional regulation of the beta 3 tubulin gene by 20-hydroxyecdysone in Drosophila Kc cells.

We have studied the transcriptional regulation of the beta 3 tubulin gene by the steroid hormone 20-hydroxyecdysone (20-E) in Drosophila Kc cells. A series of hybrid genes, with different fragments of the beta 3 tubulin gene driving the bacterial chloramphenicol acetyl transferase (CAT) gene were constructed. The promoter activity was assayed after transient expression in Kc cells, in the presence and the absence of 20-E. Constructs with 0.91 kb upstream from the transcription start site and 360 bp from the first large intron allowed the hormonal regulation, i.e. a repression in the absence of 20-E and a derepression-activation in the presence of the hormone. This 360 bp fragment contains several enhancers and silencer(s) sequences. The regulation of the expression of the beta 3 tubulin gene results from the combined activity of all the positive and negative regulatory sequences of the first intron, and a dialogue with the promoter sequences. The nucleotide sequence of this intronic regulatory-fragment has been established and we have identified several EcRE (ecdysone responsive element) consensus sequences.

Animals↗
PubMed1993

Electrocardiography in epilepsy patients without cardiac symptoms.

Sudden unexpected death in epilepsy (SUDEP) has been ascribed to cardiac arrhythmia, possibly triggered by cerebral events. Young, noncompliant, substance-abusing males with convulsions may be at risk. EEG/ECG studies have not shown significant cardiac arrhythmias in these and other seizure patients. We reviewed resting ECGs in 75 epilepsy patients and compared ventricular rate, PR interval, QRS duration, and QT interval corrected for heart rate (QTC) with normal ECGs recorded in age-matched patients without cardiac or neurologic disorders. No potentially lethal arrhythmias were noted in the seizure patients. Patients who fit the previously-described profile of high risk of SUDEP had more abnormal ECGs and ventricular rate was faster in these patients than in other epileptics. Patients with complex partial and secondarily generalized seizures had faster ventricular rates than other epileptics. No differences were noted in QRS duration or PR interval. QT was longer in patients with complex partial seizures than in control ECGs or other epileptic patients. These findings suggest that resting ECG has low diagnostic yield in epilepsy patients without cardiac symptoms. The factors possibly predisposing to SUDEP may relatively increase resting heart rate, however, and relatively increased QT interval with complex partial seizures may indicate some differences, possibly neurally-mediated, in cardiac excitability which could contribute to SUDEP.

Adult↗
PubMed1993

Neuropsychological and event-related potential correlates of nonepileptic seizures.

A retrospective study of 14 patients with epileptic seizures and 11 with nonepileptic seizures, all taking antiepileptic drugs, found epileptic patients had significantly longer P160, N200, and P300 latencies on auditory event-related potential recordings. Patients with nonepileptic seizures had generally higher IQs and significantly greater psychopathology on neuropsychological scales.

Acoustic Stimulation↗
PubMed1993

Electroencephalography in childhood conduct and behavior disorders.

The pathophysiology of behavior disorders in children is controversial. In particular, the relationship of episodic behavior disturbance to epilepsy and chronic behavior problems to subclinical neurologic disorder has been debated. It has been suggested that EEG may assist in this sometimes difficult determination. We report on routine screening EEGs in children hospitalized over an 18-month period for behavior problems. Eighty-six children were admitted for conduct disorder, attention deficit hyperactivity disorder, or both. Seventy-eight tracings (91%) were normal or showed normal variant patterns. Eight records (9%) were abnormal, showing background slowing or paroxysmal discharges not associated with behavioral manifestations. None of these neurologically normal, nonretarded patients had epilepsy or other known cerebral disorder. This suggests that routine EEG screening may be of limited value in childhood behavior problems without clinical evidence of neurologic disorder.

Adolescent↗
PubMed1993

Contingent negative variation in Gilles de la Tourette syndrome.

The Contingent Negative Variation (CNV) may measure arousal and attention, and is affected by various dopaminergic disorders. We recorded CNVs in 12 patients fulfilling diagnostic criteria of Gilles de la Tourette Syndrome (TS). Ten of 12 patients were male, 10 had attention deficit disorder (ADD), and 3 also had obsessions and compulsions (OCD). Medication had been stopped or TS treatment not yet started. TS patients had higher CNV amplitude and more frequent postimperative negative variation than controls. CNV2 was enhanced in all TS patients, while CNV1 was attenuated in TS patients with ADD or OCD. This suggests that CNV may be increased in TS, mostly because of CNV2 and perhaps due to dopaminergic excess. CNV2, considered to reflect adrenergic arousal mechanisms, may be effected by neurobehavioral concomitants of TS. Neurophysiological categorization of TS patients may be possible and valuable.

Adolescent↗
PubMed1993

Mozart's chronic subdural hematoma.

No commemoration of the bicentennial of Mozart's death would be complete without some consideration of that premature yet predictable demise. Mozart's premonitions of death are well known and apparently played a role in the composition of the K.626 Requiem and perhaps other works. His death has traditionally been ascribed to infectious causes, chiefly rheumatic fever or post-streptococcal glomerulonephritis, exacerbated by intemperance and chronic penury. Pathology has been difficult because of his supposed burial in a pauper's grave, the location and contents of which were later supposedly lost. Mozart's burial place in St. Mark's Cemetery in Vienna was known and, in the parlance of the day, "reorganized" a decade later, as the occupants of plots were disinterred to make room for the more recently decreased. A skull believed to the Mozart's was saved by the successor of the gravedigger who had supervised Mozart's burial, and then passed into the collections of the anatomist Josef Hyrtl, the municipality of Salzburg, and the Mozarteum museum (Salzburg). Forensic reconstruction of soft tissues related to this skull reveals substantial concordance with Mozart's portraits. The skull suggests premature closure of the metopic suture, which has been suggested on the basis of his physiognomy. A left temporal fracture and concomitant erosions raise the question of chronic subdural hematoma, which would be consistent with several falls in 1789 and 1790 and could have caused the weakness, headaches, and fainting he experienced in 1790 and 1791. Aggressive bloodletting to treat suspected rheumatic fever could have decompensated such a lesion to produce his death on December 5, 1791.

Austria↗
PubMed1992

Neuropsychological and psychiatric correlates of intractable pseudoseizures.

Psychogenic seizures can mimic convulsive epilepsy and with repetitive attacks, iatrogenic complications from aggressive treatment of status epilepticus can occur. We studied neuropsychiatric features of 20 patients in whom psychogenic seizures were intractable and at times continuous. Nineteen of 20 patients seen were female, and all but one were under 40 years of age. All had convulsive attacks resistant to various medications, normal neurological examinations, and negative imaging studies and electroencephalograms (EEGs). Sixteen had previous evidence of epilepsy and the other four had epileptic relatives. Seizures were atypically prolonged, included back arching and pelvic thrusting, and persisted despite intravenous diazepam and therapeutic phenytoin and phenobarbital levels. Seizures terminated spontaneously in five, were stopped by suggestion in four, and persisted until respiratory arrest or elective intubation in 11. Ten patients had conversion disorder, six borderline or mixed personality disorder and four mental retardation. Fifteen had had some precipitating stressor and the remainder had histories of exhibiting attention-seeking behaviour. Nine of 10 patients with conversion disorder had 'conversion V' Minnesota Multiphasic Personality Inventory (MMPI) profiles, while personality disorder patients had elevation of several psychopathological scales. Patients with conversion disorder gradually improved with anticonvulsant discontinuation, while retarded individuals were helped by behaviour modification, situational change or neuroleptics. Personality disorder patients continued to have attacks and eventually discontinued follow-up. Clinical evidence of non-epileptic seizures includes clinical atypicality and long duration, exacerbation by medications and frequent attacks despite normal examination and studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

ATP overflow from the mouse isolated vas deferens.

1. A modified form of the highly specific luciferin-luciferase assay was used to measure the overflow of adenosine 5'-triphosphate (ATP) from the field-stimulated mouse vas deferens in vitro. Precise timing of the stimulation, superfusate collection and assay minimized ATP degradation before assay, offering the opportunity for quantitative studies. 2. Stimulation with between 50 and 200 supramaximal pulses at 5 Hz increased ATP overflow by between 7 and 28 times over basal. 3. ATP overflow increased steadily with increasing numbers of stimuli from 50 to 200 pulses. Increasing the frequency of stimulation initially had no effect, but above 10 Hz there was increased overflow, suggesting an interaction between facilitated release and the rate of degradation by extracellular ATPases. 4. Contractions of the vas induced by exogenous (-)-phenylephrine produced only a small increase in ATP overflow, suggesting that the stimulation induced increase in ATP overflow is mostly pre-junctional in origin, though tetrodotoxin eliminated stimulation-induced overflow only in a proportion of preparations.

Adenosine Triphosphate↗
PubMed1992

EEG and evoked potentials in episodic-dyscontrol syndrome.

The neurophysiologic correlates of explosive rage and violence are uncertain and controversial. We recorded 17-channel electroencephalograms (EEGs), brainstem auditory-evoked potentials (BAEPs), and long-latency auditory-event-related potentials (AEPs) in 23 patients with impulsive, aggressive and violent behavior satisfying criteria for episodic-dyscontrol syndrome. Most patients also satisfied criteria for intermittent explosive disorder, although some had had conduct disorders in childhood or had previously used psychoactive substances. Sixteen of 23 patients had normal EEGs, while 7 had diffuse or focal slowing not ascribable to drowsiness or the effects of medication. They differed significantly from 20 age-matched patients with headaches, of whom 1 had an abnormal EEG (chi 2 = 4.68, p < 0.05), and from 24 depressed patients, all of whose EEGs were normal (chi 2 = 4.83, p < 0.05). Patients and normal control subjects did not differ in BAEP latencies. N100 and P160 AEP amplitudes were lower in episodic-dyscontrol patients than in control, but the difference was not significant. These findings suggest that non-specific cerebral dysfunction and EEG changes may be associated with disordered impulse or behavior control. Episodic dyscontrol may be associated with other evidence of minimal brain dysfunction.

Acoustic Stimulation↗
PubMed1992

Auditory evoked potentials in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (TS) has been increasingly studied neurophysiologically as well as clinically. Obsessive-compulsive disorder (OCD) and attention deficit disorder (ADD) have been recognized to be part of the continuum of TS. We recorded brainstem auditory evoked potentials (BAEPs) and long-latency auditory event-related potentials (ERPs) in 20 patients with TS, 10 of whom had ADD and 6 OCD. TS patients with and without OCD and ADD did not differ in BAEP latencies, and no differences were found from normal controls. AEP latencies did not differ between TS patients and controls. TS patients with ADD had longer N100 and N200 latencies than TS patients without ADD, and TS patients with OCD had shorter N200 and P300 latencies. These findings suggest that TS is neurophysiologically heterogenous, and that TS patients with OCD or ADD may differ from those without.

Adolescent↗
PubMed1992

Cassette EEG sleep recordings in Gilles de la Tourette syndrome.

Tourette syndrome (TS) patients often complain of sleep problems, and questionnaire studies indicate that sleep disturbance is frequent. Decreased slow wave sleep and increased awakenings have been reported in laboratory polysomnography in TS patients, and a serotoninergic disorder of arousal has been postulated. We recorded outpatient sleep in 20 patients newly diagnosed with TS utilizing a 4-channel cassette EEG system. The newly-diagnosed patients were predominantly male, and ranged in age from 10 to 36 years. Some had taken psychotropic medications in the past, but none had been treated systematically for TS. Seven patients had chronic tics only, 8 had tics and attention deficit-hyperactivity, and 5 had tics plus obsessions and compulsions. None had other medical, neurologic, or psychiatric disorders. All were nocturnal sleepers, and were recorded in their usual sleeping environments and routines. TS patients had reduced sleep, decreased sleep efficiency, increased awakenings, and decreased slow wave sleep. Tic patients had increased nocturnal awakenings and movements, particularly those who had tics during sleep. Sleep fragmentation and loss of slow wave sleep was most marked in TS patients with attention deficit-hyperactivity. Sleep latency was increased, REM sleep reduced, and REM sleep latency decreased in TS patients with obsessions and compulsions. These findings accord with previous reports of sleep disturbance in TS, and suggest that these disturbances may vary with TS symptoms. Chronic tics may persist in sleep and cause awakenings, TS with attention deficit may be associated with a disorder of arousal and alertness, and obsessions and compulsions may be manifestations of a biochemical disturbance involving paradoxical sleep.

Adolescent↗
PubMed1992

Neurophysiologic studies in nightmare sufferers.

Nightmares have long attracted neurologic and psychiatric attention, yet little is known of their pathophysiology. We recorded 17-channel electroencephalograms (EEGs), brainstem auditory evoked potentials (BAEPs), long-latency auditory event-related potentials (AEPs), and overnight cassette sleep EEGs (AEEGs) in 10 individuals with recurrent nightmares. They were all nocturnal sleepers, took no medications, do not abuse alcohol or drugs, and had no known medical or psychiatric illnesses. Five patients were being evaluated for other complaints, 3 reported disturbed nocturnal sleep and daytime sleepiness, and 2 sought attention chiefly for nightmares. All 10 patients had normal EEGs and BAEPs. BAEP latencies did not differ significantly from control subjects. Latencies and amplitudes of AEPs were not significantly different in nightmare sufferers and controls, but the former had higher amplitude N100, P160, and N200. Those patients with sleep complaints had on overnight AEEG, less sleep, decreased slow-wave sleep, and more awakenings than those without sleep complaints, but nightmares did not occur during the AEEG recordings.

Adolescent↗
PubMed1992

Passive long-latency event-related potentials in mental retardation.

Long-latency auditory event-related potentials (ERPs) were passively recorded in ten mental retardates and ten age-matched normal controls. Patients were mildly to moderately retarded and had epilepsy controlled with monotherapy, ERPs were recorded from CA-A1+A2, with 1000 and 3000 Hz tones in an "oddball" paradigm. Latency and amplitude of N1, N2, P2, and P3 components were compared in controls and retardates. All ten patients had reproducible AEPs, but these were attenuated in amplitude in four, although amplitudes did not differ significantly from controls. P3 was prolonged in latency in four patients, but patients and controls did not differ significantly. AEP latency and amplitude was not correlated with degree of retardation. These findings suggest that "cognitive" evoked potentials an be recorded passively in persons with impaired cognition, but are not correlated with intellectual ability and may not reflect specific cognitive functions.

Adult↗
PubMed1991

Auditory evoked potentials in anxiety disorder.

The pathophysiology of anxiety has received much recent attention. EEG findings in anxiety are nonspecific, and some changes in psychophysiological measures have been reported. We recorded short-latency brainstem auditory evoked potentials (BAEPs) and long-latency auditory event-related potentials (AEPs) in 12 patients with generalized anxiety disorder. All 12 patients had BAEP latencies within clinical norms, but I-V interpeak latencies were significantly longer in patients with anxiety than controls. N1, N2, P2, and P3 AEP components were within normal limits; N1 and P2 were reduced in amplitude in anxiety patients, but differences from controls were not significant. The BAEP findings may suggest altered brain-stem function in anxiety, which has been implied by biochemical studies of anxiety and depression. AEP differences may be related to difficulties in concentration and attention direction reported by anxious patients.

Adult↗