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Biomedical subjects

M J Morrell

Publications and source records attributed to M J Morrell.

At least 55 records · Page 3Linked to original sources
PubMed1998

Progressive retropalatal narrowing preceding obstructive apnea.

Pharyngeal occlusion during obstructive apnea is thought to be an inspiratory-related event; however, occlusion also occurs in the absence of negative intrathoracic pressure. We hypothesized that inspiratory-related pharyngeal occlusion would be preceded by significant expiratory narrowing. Eight sleeping patients with obstructive apnea were studied. Pharyngeal caliber, airflow, and esophageal pressure (Pes) were simultaneously monitored during three to four consecutive breaths preceding occlusion (between 3 and 22 events were studied per subject). Relative changes in retropalatal airway cross-sectional area (CSA) were determined from fiberoptic images (five frames per second) normalized to the maximum CSA. During inspiration, CSA was significantly reduced only during the breath immediately preceding the apnea (Group mean CSA +/- SEM: 51 +/- 8% at the start of inspiration compared with 37 +/- 8% at midinspiration). During expiration, for all breaths there was an initial significant increase in CSA compared with the nadir CSA during the preceding inspiration (CSA: breath-3, 57 +/- 10% to 79 +/- 3%; breath-2, 59 +/- 8% to 76 +/- 4%; breath-1, 37 +/- 8% to 64 +/- 8%), followed by a significant narrowing at end-expiration compared with the peak CSA during that expiration (CSA: breath-3, 79 +/- 3% to 62 +/- 6%; breath-2, 76 +/- 4% to 50 +/- 10%; breath-1, 64 +/- 8% to 36 +/- 10%). Occlusion occurred at a pressure significantly less than that generated during the previous unoccluded breath (Pes: breath-1, -10.8 +/- 2.9 cm H2O; occlusion, -8.2 +/- 1.9 cm H2O). These results show that expiratory narrowing produced a significant reduction of CSA at end-expiration prior to obstructive apnea.

Adult↗
PubMed1998

Analysis of prenatal and gestational care given to women with epilepsy.

OBJECTIVE: To assess past care practices of neurologists and obstetricians to identify areas in which practice patterns differ from currently accepted optimal care. METHODS: Retrospective chart review of 155 women identified as having a diagnosis of epilepsy (or seizure disorder) who had been pregnant any time between January 1988 and December 1995 and were admitted to Stanford University Hospital for delivery. A total of 161 pregnancies (132 women) were selected for study. RESULTS: An obstetrician was seen at some point during the pregnancy in 99% of the pregnancies, whereas a neurologist was seen at least once in only 64% of the pregnancies. In the 3 months before conception, an obstetrician was seen in 5% of the pregnancies and a neurologist was seen in 15%. Seventy-five percent of the patients taking antiepileptic medication and 65% of the untreated patients had documentation of folate supplementation at any time during pregnancy. Vitamin K supplementation in the final month of pregnancy was documented for only 41% of those receiving antiepileptic drugs. In over one-third of the pregnancies the mother did not have a maternal serum alpha-fetoprotein measure documented and a similar percentage did not receive genetic counseling. Monitoring of the maternal serum concentration of the non-protein-bound fraction of the prescribed antiepileptic drugs was not documented. CONCLUSIONS: We identified specific omissions of appropriate vitamin supplementation, genetic counseling, and drug level monitoring. Educational efforts should be targeted to improve the management of pregnancy in women with epilepsy.

Abortion, Induced↗
PubMed1998

Management issues for women with epilepsy: a review of the literature.

OBJECTIVE: A review of literature referable to management issues for women with epilepsy (WWE) was undertaken for the development of a practice parameter. BACKGROUND: Epilepsy is a common neurologic condition with gender-related management implications. Although reviews of this topic often focus on pregnancy-related issues for WWE, specific health concerns for WWE are present throughout all phases of reproductive life. METHODS: An OVID MEDLINE literature search was conducted for 1965 to 1997 using the following key words/phrases and cross referencing: epilepsy/ seizures and pregnancy, anticonvulsants, antiepileptic drugs (AEDs), teratogenesis, oral contraceptives, birth defects, folate/folic acid, vitamin K, metabolic bone disease, and breast-feeding. RESULTS: Pregnancy outcome literature for WWE spans several decades. Methodology varies and interpretation is complicated by modern management strategies. Contributions of socioeconomic factors, AEDs, maternal epilepsy, and seizures during pregnancy to adverse pregnancy outcomes have not been clearly delineated. There is a biologic basis for recommendations concerning contraception, folate supplementation, vitamin K use in pregnancy, breast-feeding, metabolic bone disease, catamenial epilepsy, and reproductive endocrine disorders, but no outcome studies afford a strong evidence base for practice recommendation. CONCLUSIONS: WWE face health issues for which there is no available outcome literature to guide decision making. The urgent need for studies in many of these areas is highlighted by expanded treatment options with new AEDs and epilepsy surgery.

Anticonvulsants↗
PubMed1998

Guidelines for the care of women with epilepsy.

Antiepileptic drug (AED) selection in women of reproductive age should consider efficacy, tolerability, interactions with contraceptive medications, and teratogenicity. Women planning a pregnancy should be counseled regarding the need for compliance with therapy and the risk for birth defects. All women with epilepsy who are of childbearing potential should receive folate supplementation. Vitamin K supplementation is recommended during the final month of pregnancy. Withdrawal of AED therapy in seizure-free women can be considered before conception. Women who require AED therapy should receive AED monotherapy rather than polytherapy when at all possible. Medication changes post conception do not significantly reduce the risk for major fetal malformations and may compromise seizure control. Breastfeeding is generally safe for women taking AEDs. Menstrual disorders, reproductive endocrine disorders, ovulatory dysfunction, and infertility appear to be relatively common in women with epilepsy.

Abnormalities, Drug-Induced↗
PubMed1997

Effect of induced hypocapnic hypopnea on upper airway patency in humans during NREM sleep.

We wished to determine the effect of reduced ventilatory drive (hypopnea) on upper airway patency in humans during non-rapid-eye-movement (NREM) sleep. We studied nine subjects (58 trials) spanning the spectrum of susceptibility to upper airway collapse including normals, snorers and patients with mild sleep apnea. Hypocapnic hypopnea was induced by abrupt cessation of brief (1 min) nasal mechanical hyperventilation. Surface inspiratory EMG (EMGinsp) was used as an index of drive. Upper airway resistance and supraglottic pressure-flow plots were used as indexes of upper airway patency. Termination of nasal mechanical ventilation resulted in reduced VE to 4904 of pre-mechanical ventilation eupneic control. Upper airway resistance at a fixed flow did not change significantly in inspiration or expiration. Likewise, pressure-flow plots showed no increase in upper airway resistance except in one subject. However, maximum flow (Vmax) decreased during hypopnea in four subjects who demonstrated inspiratory flow-limitation (IFL) during eupneic control. In contrast, no IFL was noted in subjects who showed no evidence of IFL during eupnea. We concluded: (1) Reduced ventilatory drive does not compromise upper airway patency in normal subjects during NREM sleep; (2) the reduction in Vmax during hypopnea in subjects with IFL during eupneic control, suggests that reduced drive is associated with increased upper airway compliance in these subjects; and (3) upper airway susceptibility to narrowing/closure is an important determinant of the response to induced hypopnea during NREM sleep.

Adult↗
PubMed1997

Intracranial ictal recordings in Mesial frontal lobe epilepsy.

Localization of ictal onset in patients with medically refractory frontal lobe epilepsy is challenging even with intracranial monitoring. We present a series of nine patients with presumed mesial frontal lobe epilepsy in whom successful localization of ictal onset was achieved in most cases. Intracranial electrodes were placed over cingulate and supplementary motor cortex bilaterally, with additional electrodes placed over lateral and inferior frontal lobes as part of an evaluation for epilepsy surgery. Localization of the ictal onset was clearly defined in seven of nine patients and was characterized by a pattern of lower amplitude beta/gamma range frequencies noted in one to four adjacent electrodes arising from cingulate cortex or supplementary motor cortex in six patients. In the remaining patient, ictal onset was characterized by periodic high amplitude spike and slow-wave discharges evolving into a higher voltage faster rhythm. Electrographic onset occurred coincident with or preceded clinical findings. Ictal pattern also did not demonstrate a widespread propagation pattern in most of the recordings in which ictal onset was well localized. Precise localization of ictal onset within the mesial frontal lobe is possible. Rapid propagation to regions within and outside the frontal lobe does not always occur.

Adolescent↗
PubMed1997

Cortical and hippocampal volume deficits in temporal lobe epilepsy.

PURPOSE: To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE). METHODS: Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3-mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA). RESULTS: As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe. CONCLUSIONS: Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.

Adolescent↗
PubMed1997

Maximizing the health of women with epilepsy: science and ethics in new drug development.

Issues of unique concern to women with epilepsy largely arise from gender-based physiological differences. Female sex steroid hormones may alter the expression of epilepsy and the efficacy of antiepileptic drugs (AEDs). Seizures and AEDs in turn affect the hypothalamic-pituitary axis and can adversely impact reproductive function and bone health. Maternal seizures and exposure to AEDs may compromise fetal development. At this time, women with epilepsy and their medical caretakers do not have access to all the information necessary to formulate a treatment plan that will have the least impact on reproductive and general health. In part, this is because reproductive aged women are excluded from the earliest phases of drug testing and pregnant and lactating women are excluded from all aspects of new drug development. Therefore, as new AEDs enter the marketplace, women with epilepsy must decide whether a new AED is appropriate for therapy based on very limited information. Postmarketing surveillance of gender-specific adverse effects, as with all adverse effects, depends on voluntary reporting. Only a small percentage of significant adverse events are believed to be captured by the present system. Consumers, ethicists, and some physician groups are now arguing that women should be included in all aspects of the development of drugs they will ultimately use-even pregnant and lactating women. Some of the issues of concern for women with epilepsy regarding epilepsy treatment, reproductive function and general health will be reviewed, followed by a discussion of the drug development process and how it does, and could better, address the concerns of women.

Adult↗
PubMed1997

Gabapentin monotherapy: I. An 8-day, double-blind, dose-controlled, multicenter study in hospitalized patients with refractory complex partial or secondarily generalized seizures. The US Gabapentin Study Group 88/89.

We evaluated the efficacy and safety of gabapentin administered as monotherapy in an 8-day, randomized, double-blind, dose-controlled, parallel-group, multicenter study comparing dosages of 300 and 3,600 mg/d gabapentin in 82 hospitalized patients whose antiepileptic medications had been discontinued for seizure monitoring. Seizures under study were complex partial seizures with or without secondary generalization. Patients exited the study if they experienced a protocol-defined exit event indicating lack of efficacy. Time to exit was significantly longer (p = 0.0001) and completion rate was significantly higher (53% versus 17%; p = 0.002) for patients receiving 3,600 mg/d gabapentin. Gabapentin was well tolerated by patients in both dosage groups, and no patients exited the study due to adverse events, despite rapid initiation of full dose within 24 hours. These results demonstrate that gabapentin has anticonvulsant activity and is well tolerated when administered as monotherapy in patients with refractory partial seizures.

Acetates↗
PubMed1997

Simultaneous digitization of upper airway fiber-optic images and respiratory signals.

We developed an inexpensive and efficient method for simultaneously digitizing respiratory signals and fiber-optic images of the upper airway. The main components of the system are a fiber-optic scope, a charge coupled device video camera, and a personal computer equipped with a frame grabber and an A/D board. The frame grabber digitizes images at five frames per second while the A/D board samples six respiratory signals at 25 samples per second. Digitized images are saved only in the event that the user instructs the computer to do so in order to limit disk space requirements. A circular buffering technique provides continuous storage of the most recent 50 frames in frame grabber memory. This feature gives the user up to 10 seconds, following the beginning of a respiratory event, to initiate the saving of images to computer hard disk. A postacquisition program displays the data acquired during the sleep study and allows the user to interactively select images for subsequent upper airway area measurement. This system enables us to observe and quantify the dynamics of the upper airway during different breathing conditions with minimal time and cost. It is also a potential clinical tool to use to determine the site of obstruction during sleep in patients with obstructive sleep apnea.

Computers↗
PubMed1996

Control of breathing in man; insights from the 'locked-in' syndrome.

Control of breathing was studied in a patient with a lesion in the ventral pons; no volitional behaviour, including voluntary breathing acts, was possible (locked-in syndrome, LIS). Spontaneous breathing via a tracheostomy maintained a normal PETCO2 of 39-40 mmHg. Variability of ventilatory parameters awake was similar to that seen in five tracheostomized control subjects during stage IV sleep but much smaller than during resting wakefulness. Emotion associated with laughter caused disturbances of breathing. The ventilatory response to CO2 was normal and was associated with 'hunger for air' when the PETCO2 was 49-50 mmHg. Mechanical ventilation to reduce PETCO2 by as little as 1 mmHg resulted in apnoea when the ventilator was disconnected; breathing resumed when PETCO2 crossed the threshold of 39-40 mmHg. These results demonstrate the functional dependence of the human medullary respiratory oscillator on a threshold level of PCO2 in the absence of cortico-bulbar input, even during wakefulness. The absence of such input may explain the regularity of breathing.

Adult↗
PubMed1996

Self-reported sexual function and sexual arousability in women with epilepsy.

PURPOSE: Women with epilepsy are at risk for sexual dysfunction but the frequency and types of dysfunction have not been well characterized. METHODS: Self-reported sexual function was evaluated in 116 women aged 18-65 years with epilepsy and no concomitant medical or psychiatric illness, including 99 with localization-related epilepsy (LRE) and 17 with primary generalized epilepsy (PGE). Variables evaluated included seizure frequency, age of seizure onset, and antiepileptic drug (AED) exposure. Standardized inventories assessed sexual functioning, sexual arousability and anxiety, sexual behavior, and depression. RESULTS: Although sexual experience was not reduced, women with PGE and LRE reported significantly less sexual arousability and women with LRE reported significantly more sexual anxiety. Women with LRE experienced significantly more dyspareunia, vaginismus, arousal insufficiency, and sexual dissatisfaction, whereas women with PGE experienced anorgasmia and sexual dissatisfaction. Sexual symptoms were not associated with seizure frequency, AED exposure, sexual experience, depression, or prepubertal seizure onset. CONCLUSIONS: In contrast to subjects of previous research, the women in our study did not have a disorder of sexual desire, but more than one third experienced disorders of sexual arousal, implying a physiological deficit. Although the etiology for these arousal phase dysfunctions has not been defined, such conditions are treatable and warrant referral to a gynecologist versed in the treatment of sexual disorders.

Adolescent↗
PubMed1996

Nocturnal penile tumescence and rigidity evaluation in men with epilepsy.

PURPOSE: Men with epilepsy appear to have an approximately fivefold increase in risk of erectile dysfunction (ED). We attempted to determine whether ED in men with epilepsy was due to a physiological basis and whether erectile function could be adequately evaluated with an ambulatory nocturnal penile tumescence and rigidity monitor. METHODS: The physiologic integrity of the sexual response in men with epilepsy and ED was assessed with an ambulatory nocturnal penile tumescence and rigidity monitor (NPTR). Six men with localization-related epilepsy of temporal lobe origin (TLE) and ED, 2 men with TLE and normal sexual function, and 1 man with nonepileptic seizures (NES) and ED underwent evaluation of nocturnal erections for at least 2 nights. RESULTS: Five of 6 men with TLE and complaints of ED had abnormal ambulatory NPTR evaluations. All others had normal ambulatory NPTR. All abnormal evaluations showed reduced levels of rigidity, often with normal levels of tumescence. CONCLUSIONS: Previous studies have shown this abnormal ambulatory NPTR pattern to be associated with neurogenic rather than vasogenic ED. Therefore, epilepsy-related ED may have a substantial neurophysiologic component.

Adolescent↗
PubMed1996

The new antiepileptic drugs and women: efficacy, reproductive health, pregnancy, and fetal outcome.

As new antiepileptic drugs (AEDs) become available, physicians will define their appropriate use in particular patient populations. For women, the issues include gender-specific efficacy and tolerability, including the impact of the AED on reproductive health. Women with epilepsy who are treated with established AEDs appear to be at risk for compromised bone health, for disturbances in fertility, menstrual cyclicity, ovulatory function, and sexuality and, with some AEDs, for failure of hormonal contraception. Finally, pregnancy outcome may be adversely affected by the established AEDs, all of which are human teratogens. Felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OCBZ), tiagabine (TGB), topiramate (TPM), and vigabatrin (VGB) were reviewed. The preclinical development process had not addressed all the issues of concern to women. Although gender-specific efficacy is routinely evaluated, impact on reproductive health is not. FBM, GBP, LTG, TGB, TPM, and VGB have similar efficacy in women and men. It is not known whether the new AEDs will affect bone health, fertility, the menstrual cycle, and sexuality. FBM, GBP, LTG, TGB, and probably VGB do not interfere with hormonal contraception. Whether these new AEDs are good choices for the pregnant woman with epilepsy awaits further experience in human pregnancy. However, animal reproductive toxicology studies appear promising. The limited number of human pregnancy exposures do not, thus far, signal a significant number or particular type of adverse outcomes. However, only with improved postmarketing surveillance can essential information about teratogenic effects by acquired in an acceptably short time.

Abnormalities, Drug-Induced↗
PubMed1996

Breathing during wakefulness and NREM sleep in humans without an upper airway.

The increase in PCO2 that occurs during sleep may reflect an inadequate ventilatory compensation to an increase in upper airway resistance. To address this question in humans, we examined changes in breathing during wakefulness and non-rapid-eye-movement sleep in eight laryngectomized subjects who breathed through a tracheal stoma. In these subjects, any sleep-related increase in upper airway resistance could not affect ventilation. Healthy subjects breathing via an intact upper airway were studied as controls. The mean increase in end-tidal PCO2 from wakefulness to sleep was 2.7 +/- 2.6 (SD) Torr (P = 0.05) in laryngectomized subjects and 1.6 +/- 1.4 Torr (P = 0.02) in control subjects. During wakefulness, ventilation was lower in laryngectomized subjects compared with control subjects, although this difference was not statistically significant (6.8 +/- 1.9 vs. 7.4 +/- 1.2 l/min; P > 0.05). During sleep, the fall in ventilation was similar in the two groups (1.1 +/- 2.1 vs. 0.8 +/- 2.1 l/min; P > 0.05). Our observations are not consistent with the view that increases in upper airway resistance are obligatory for sleep-related CO2 retention in humans.

Aged↗
PubMed1996

Cerebellar hemorrhage complicating temporal lobectomy. Report of four cases.

Four cases of cerebellar hemorrhage complicating temporal lobectomy are presented. A case of postoperative hemorrhage located remote from the operative site as a complication of intracranial surgery is rare, especially when it involves the cerebellum after supratentorial craniotomy. In a review of the literature, the authors identified only 12 such cases, none of which was described in the setting of a temporal lobectomy. The possible etiologies for cerebellar hemorrhage in the four cases presented are examined, including the role of epidural suction drains and the position of the head during surgery. The mechanism of cerebellar hemorrhage in this series of patients is probably multifactorial. Special attention throughout the perioperative course must be given to hemodynamic, anatomical, and physiological factors that together can affect the patient negatively.

Adolescent↗