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Biomedical subjects

M J Morrell

Publications and source records attributed to M J Morrell.

At least 37 records · Page 2Linked to original sources
PubMed2001

Impact of age on breathing and resistive pressure in people with and without sleep apnea.

We investigated the effect of age on breathing and total pulmonary resistance (RL) during sleep by studying elderly (>65 yr) and young (25-38 yr) people without sleep apnea (EN and YN, respectively) matched for body mass index (BMI). To determine the impact of sleep apnea on age-related changes in breathing, we studied elderly and young apneic patients (EA and YA, respectively) matched for apnea and BMI. In all groups (n = 11), breathing during periods of stable sleep was analyzed to evaluate the intrinsic variability of respiratory control mechanisms. In the absence of sleep apnea, the variability of the breathing was similar in the elderly and young [mean (+/- SD) coefficient of variation (CV) of tidal volume (VT); wake: EN 21.0 +/- 14.9%, YN 14.7 +/- 5.5%; sleep: EN 14.0 +/- 6.0%; YN 11.5 +/- 6.4%]. In patients with sleep apnea, breathing during stable sleep was more irregular, but there were no age-related differences (CV of VT; wake: EA 22.0 +/- 11.6%, YA 16.7 +/- 11.3%; sleep: EA 32.8 +/- 24.9%, YA 25.2 +/- 16.3%). In addition, EN tended to have a higher RL (n = 6, RL midinspiration, wake: EN 7.1 +/- 3.0; YN 9.1 +/- 6.4 cmH(2)O. l(-1). s, sleep: EN 17.5 +/- 11.7; YN 9.8 +/- 2.0 cmH(2)O. l(-1). s). We conclude that aging per se does not contribute to the intrinsic variability of respiratory control mechanisms, although there may be a lower probability of finding elderly people without respiratory instability.

Adult↗
PubMed2001

Adverse effects of antiepileptic drugs on bone structure: epidemiology, mechanisms and therapeutic implications.

Antiepileptic drugs (AEDs) were first associated with disorders of bone in both adults and children in the late 1960s. The most severe manifestations of these disorders are osteopenia/osteoporosis, osteomalacia and fractures. Bone disease has been described in several groups of patients receiving AEDs. Groups identified as being more vulnerable to AED-associated bone disease include institutionalised patients, postmenopausal women, older men and children. Radiological and histological evidence of bone disease is found in patients taking AEDs. Numerous biochemical abnormalities of bone metabolism have also been described. The severity of bone and biochemical abnormalities is thought to correlate with the duration of AED exposure and the number of AEDs used. In monotherapy, the AEDs most commonly associated with altered bone metabolism are phenytoin, primidone and phenobarbital (phenobarbitone). To date there have been no reports of altered bone metabolism in individuals receiving the newer anticonvulsants (specifically lamotrigine, topiramate, vigabatrin and gabapentin). The mechanisms of AED-associated bone disease are not clearly elucidated; however, several theories have been proposed to explain the link. No definitive guidelines for evaluation or treatment have yet been determined.

Anticonvulsants↗
PubMed2000

The respiratory response to inspiratory resistive loading during rapid eye movement sleep in humans.

We investigated the respiratory response to an added inspiratory resistive load (IRL) during rapid eye movement (REM) sleep in humans and compared this with those in non-REM (NREM) sleep and wakefulness. Results were obtained from 7 out of 15 healthy subjects (n = 7; 32 +/- 9 years, mean +/- s.d.). Linearised IRLs (4 and 12 cmH(2)O l(-1) s(-1)) were applied for five breaths during NREM sleep (4-10 trials per subject; total 101), REM sleep (2-5 trials; total 46) and wakefulness (2-3 trials; total 40). Respiratory variables were compared, between unloaded breathing (UL: mean of 5 breaths preceding IRL) and the 1st (B1) and 5th (B5) loaded breaths in each state. During wakefulness, 12 cmH(2)O l(-1) s(-1) IRL produced an immediate respiratory compensation with prolongation of inspiratory time (T(I); UL: 2.0 +/- 0.6; B1: 2.6 +/- 0.7 s) and an increase in tidal volume (V(T); UL: 0.49 +/- 0.12; B1: 0.52 +/- 0.12 l). During REM sleep, T(I) was prolonged (UL: 2.0 +/- 0.3; B1: 2.2 +/- 0.5 s), although V(T) fell (UL: 0.27 +/- 0.15; B1: 0.22 +/- 0.10 l). For both wakefulness and REM sleep the TI response was significantly greater than seen in NREM sleep (UL: 1.9 +/- 0.3; B1: 1.9 +/- 0.3 s.). For VT, only the wakefulness response was significantly different from NREM sleep (UL: 0.31 +/- 0.14; B1: 0.21 +/- 0.10 l). The B5 responses were not significantly different between states for any of the variables. REM sleep is associated with partial respiratory load compensation suggesting that exacerbation of sleep disordered breathing in REM (compared to NREM) sleep is unlikely to be secondary to an inability to overcome increases in upper airway resistance.

Adult↗
PubMed2000

Efficacy of gabapentin as adjunctive therapy in a large, multicenter study. The Steps Study Group.

The objective of this study was to determine the efficacy of gabapentin as adjunctive therapy in doses required to achieve the most effective seizure control. There were 2016 patients with partial seizures requiring adjunctive therapy who received gabapentin at doses up to 3600 mg/day in this open-label, multicenter, 16-week study. Of the 1055 patients evaluable for efficacy, 573 received gabapentin < or =1800 mg/day and 482 received > 1800 mg/day as the highest dose received. For the overall efficacy evaluable population, the percentage of patients achieving at least a 50% reduction in seizure frequency was 76.0%; 46.4% of the patients were seizure free. Patients whose highest gabapentin dose did not require > 1800 mg/day had, at baseline, fewer seizures and were receiving fewer concomitant antiepileptic drugs (AEDs) at baseline than those patients requiring > 1800 mg/day. This suggests that patients requiring higher doses of gabapentin were more refractory to drug treatment at the start of the study. Gabapentin was well tolerated at all doses in this study. The results of the study demonstrate that gabapentin is effective as adjunctive therapy in patients with partial seizures whose seizures are inadequately controlled by traditional AEDs.

Acetates↗
PubMed2000

Health issues for women with epilepsy: a descriptive survey to assess knowledge and awareness among healthcare providers.

The American Academy of Neurology and the American College of Obstetricians and Gynecologists recently issued practice parameters for women with epilepsy. These parameters suggest optimal care practices. To assess knowledge of the issues covered in the parameters and to facilitate educational efforts to promote best care, the Epilepsy Foundation conducted a survey of healthcare professionals likely to provide care to women with epilepsy. The survey sampled 3535 healthcare professionals across a wide range of specialties. Most respondents did not know the specific effects of estrogen and progesterone on the seizure threshold, were not aware of menstrual-associated seizure patterns, and could not identify which antiepileptic drugs interfere with oral contraceptives. The majority of respondents did not know that women with epilepsy have higher rates of infertility, reproductive endocrine disorders, and sexual dysfunction. Most respondents did not know the frequency of birth defects in children born to women with epilepsy. Providers seeing the largest number of persons with epilepsy were more likely to have correct answers. By specialty, neurologists provided the highest number of correct responses, followed (in descending order) by endocrinologists, obstetricians/gynecologists, internal medicine physicians, family practice physicians, and pediatricians. These results suggest that women with epilepsy are not receiving adequate counseling and that care practices may not conform to those recommended.

Attitude of Health Personnel↗
PubMed2000

The role of the intracarotid amobarbital procedure in evaluation of patients for epilepsy surgery.

PURPOSE: To examine the role of the intracarotid amobarbital procedure (IAP) in the presurgical evaluation of patients with medically refractory localization-related epilepsy. METHODS: We retrospectively studied 111 patients who underwent cortical resective surgery at our center between 1991 and 1996. In patients with mesial temporal lobe epilepsy (mTLE), a presurgical determination of the epileptogenic zone was compared with localization based on IAP memory asymmetry scores, and with ultimate localization after resective surgery. In patients with neocortical or mesial frontal epilepsy, the IAP was evaluated for evidence of unilateral or bilateral poor memory performance. RESULTS: Of 68 patients with mTLE localized by noninvasive tests, 60 had concordant lateralized memory deficits on IAP. Eight patients had lateralized memory deficits on IAP that were discordant with noninvasive tests and with localization as determined by surgical outcome. All 11 mTLE patients requiring invasive EEG monitoring were correctly lateralized by IAP, including one patient in whom the noninvasive evaluation otherwise provided false lateralization. Of 32 patients with neocortical or mesial frontal lobe epilepsy, 21 displayed memory deficits on IAP. Of 10 patients with bilateral deficits, five had mesial frontal lobe epilepsy. In 13 patients with lateralized memory deficits, seven underwent electrode implantation in the mesial temporal lobe, and four ultimately underwent resection of an epileptogenic mesial temporal lobe in addition to a neocortical resection. CONCLUSIONS: In patients with mTLE, lateralized memory deficits on IAP usually confirm localization provided by noninvasive tests. However, in mTLE not well lateralized by the noninvasive evaluation, and in neocortical or mesial frontal epilepsy, the IAP may provide information regarding localization that ultimately alters surgical management.

Adolescent↗
PubMed2000

Assessment of ganaxolone's anticonvulsant activity using a randomized, double-blind, presurgical trial design. Ganaxolone Presurgical Study Group.

PURPOSE: A double-blind, randomized, placebo-controlled clinical trial to examine the safety, tolerability, and antiepileptic activity of ganaxolone in patients after withdrawal from other antiepileptic drugs during presurgical evaluations was performed. METHODS: Fifty-two eligible patients were withdrawn from antiepileptic drugs and randomized to receive ganaxolone (24 patients) or placebo (28 patients) for up to 8 days. Ganaxolone was administered at a dose of 1500 mg/d on day 1 and 1875 mg/d on days 2 to 8. Dosing occurred three times per day: immediately after breakfast, lunch, and dinner. RESULTS: The primary measure of antiepileptic activity was duration of treatment before withdrawal from the trial. Kaplan-Meier curves depicted a clear separation between treatment groups, with 50% of the ganaxolone-treated patients completing the entire study, compared with 25% of patients treated with placebo. Intent-to-treat survival analyses revealed a trend toward efficacy with ganaxolone (p = 0.0795, log rank test). Covariate analyses revealed a significant treatment effect on survival time in men (p = 0.03). Post-hoc chi2 probe analyses focusing on patients who completed the entire study revealed a significant difference (p = 0.04) between treatment groups. The tolerability of ganaxolone was similar to that of placebo, with adverse events being reported by 79% of patients in the ganaxolone group and 68% of patients in the placebo group. CONCLUSIONS: Ganaxolone monotherapy was well tolerated for the duration of this clinical trial, and the results provide preliminary evidence that ganaxolone does have antiepileptic activity.

Adolescent↗
PubMed2000

Discriminating between epileptic and nonepileptic events: the utility of hypnotic seizure induction.

PURPOSE: To determine the validity of the Hypnotic Induction Profile (HIP) followed by seizure induction during continuous video-electroencephalographic (EEG) monitoring to discriminate between epileptic (EE) and nonepileptic events (NEE). METHODS: Eighty-two patients admitted to the Stanford Comprehensive Epilepsy Center for differential diagnosis of seizure-like events were evaluated. Exclusion criteria included inability or refusal to complete the HIP, lack of a "typical" event, an IQ <70, present evidence of psychosis, or a physiological cause for NEE. Sixty-nine patients met these criteria. While undergoing continuous video-EEG monitoring, the patient completed an HIP, an inventory designed to measure the degree of hypnotizability. An attempt was then made to induce the patient's typical events under hypnosis by using a split-screen technique. An event without an EEG correlate was thought to represent an NEE. A diagnosis of NEE was made independently by the neurology team and was compared with results obtained with the hypnotic evaluation. RESULTS: Results for patients with EE were compared with those with NEE and a group consisting of both EE/NEE. All patients with NEE were then contrasted with the EE group. HIP scores for the EE patients indicated lower hypnotizability than the NEE group and were statistically significant when NEE patients and those with NEE/EE were combined. The sensitivity of seizure induction in the diagnosis of NEE was 77%, with a specificity of 95%. CONCLUSIONS: The HIP coupled with seizure induction is a useful technique to aid in the diagnosis of patients with NEE. It is sensitive and specific, and it may provide the patient with a useful behavioral tool to control NEEs. It may also furnish a conduit for long-term treatment.

Adult↗
PubMed2000

Sleep fragmentation, awake blood pressure, and sleep-disordered breathing in a population-based study.

Arousal from sleep produces transient increases in systemic blood pressure, leading to the suggestion that repeated arousals are associated with a sustained increase in daytime blood pressure. Using data from the Wisconsin Sleep Cohort Study, a population-based study, we tested the hypothesis that sleep fragmentation is associated with elevated awake blood pressure. Sleep, breathing, and seated blood pressure measurements from 1,021 participants (age 42 +/- 8 yr; 590 males) were analyzed. Sleep fragmentation was defined as the total number of awakenings and shifts to Stage 1 sleep divided by the total sleep time (sleep fragmentation index: SFI). To reduce the confounding influence of sleep-disordered breathing, which is related to both increased daytime blood pressure and sleep fragmentation, all participants with an apnea-hypopnea index (AHI) > or = 1 were analyzed separately. Accounting for the influences of sex, age, body mass index, and antihypertensive medication use, the SFI was significantly associated with higher levels of awake systolic blood pressure in people with an AHI < 1; a 2 standard deviation increase in the SFI was associated with a 3.1 mm Hg rise in awake systolic blood pressure. In participants with an AHI > or = 1, there was no independent association between the SFI and awake blood pressure after controlling for the influence of the AHI.

Adult↗
PubMed2000

Qualitative block design performance in epilepsy patients.

Broken configuration errors on the WAIS-R Block Design subtest have been associated with right hemisphere brain damage. This study examined whether pre-surgical epilepsy patients with seizure foci restricted to the right hemisphere would break configuration more frequently than those with left hemisphere foci. Subjects included 38 patients with unilateral right or left hemisphere epilepsy of frontal or temporal lobe origin. The left and right hemisphere groups did not differ significantly in demographic or disease variables, IQ, or Block Design standard scores. Right hemisphere patients made more broken configurations than did those with left hemisphere foci. In the right hemisphere group, more broken configurations were associated with a lower Block Design Scaled Score and Full Scale IQ. These results suggest that the observation of broken configurations in the Block Design can assist in corroborating the seizure focus and highlight the importance of qualitative Block Design analysis.

Journal Article↗
PubMed1999

Safety and tolerability of gabapentin as adjunctive therapy in a large, multicenter study.

PURPOSE: To evaluate the tolerability and safety of gabapentin (GBP) as add-on therapy for seizure control. METHODS: Conducted in an outpatient setting and reflecting usual practice, this study compared tolerability of GBP dosages < or = 1,800 versus >1,800 mg/day, when these doses were required to achieve the most effective seizure control. Two analyses of adverse events are presented: tolerability and safety. In the tolerability analysis, each patient served as his or her own control to compare the occurrence of adverse events at GBP < or =1,800 versus >1,800 mg/day. The safety analysis required patients to receive at least one dose of GBP and have a follow-up contact. RESULTS: A total of 2,216 patients enrolled in this open-label, 16-week study and were evaluable for safety. Of these, 74.0% completed the 16-week study, and 281 met the tolerability criteria. Within these 281 patients, two mutually exclusive groups were compared (a) those reporting adverse events at only < or =1,800 mg/day (low dose); and (b) those reporting adverse events at only >1,800 mg/day (high dose). Three adverse events (asthenia, headache, and dizziness) were observed in a statistically significantly larger number of patients at only the low dose than in the group reporting these same adverse events at only the high dose, suggesting that patients who tolerated GBP at < or = 1,800 mg/day did not experience a significant increase in adverse events with dosages >1,800 mg/day. Overall, 10.6% of the 2,216 patients in the safety population prematurely withdrew because of adverse events, and 3.5% discontinued because of lack of efficacy. Safety and tolerability of GBP was rated as excellent or good for 78.5% of all patients. CONCLUSIONS: Gabapentin doses >1,800 mg/day were as well tolerated as doses < or =1,800 mg/day and were not associated with more adverse events.

Acetates↗
PubMed1999

Dosing to efficacy with neurontin: the STEPS trial. Study of Titration to Effect Profile of Safety.

The STEPS (Study of Titration to Effect Profile of Safety) trial, a 16-week, open-label, postmarketing multicenter study, assessed the efficacy of gabapentin as adjunctive therapy in patients with inadequately controlled partial seizures. Inclusion criteria were less restrictive than for Phase III studies, to include a population more representative of the patient population treated in clinical practice. Gabapentin was titrated up to a maximal dosage of 3600 mg/day to achieve seizure control or to tolerability. The efficacy analysis included compliant patients who had completed approximately 16 weeks of therapy (n = 1055); 573 received < or = 1800 mg/day and 482 received > or = 1800 mg/day. The average decrease in seizure frequency was 61%, the percentage of seizure-free patients was 46.35%, and the percentage of patients with a > or = 50% decrease in seizure frequency was 76.05%. The cumulative percentage of responders and of patients who were seizure free increased with each dosage increase. The results confirm that titration to efficacy is appropriate for adjunctive therapy with gabapentin in patients with partial epilepsy treated in clinical practice.

Acetates↗
PubMed1999

Unilateral focal lesions in the rostrolateral medulla influence chemosensitivity and breathing measured during wakefulness, sleep, and exercise.

OBJECTIVES: The rostrolateral medulla (RLM) has been identified in animals as an important site of chemosensitivity; in humans such site(s) have not been defined. The aim of this study was to investigate the physiological implications of unilateral lesions in the lower brainstem on the control of breathing. METHODS: In 15 patients breathing was measured awake at rest, asleep, during exercise, and during CO(2) stimulation. The lesions were located clinically and by MRI; in nine patients they involved the RLM (RLM group), in six they were in the pons, cerebellum, or medial medulla (Non-RLM group). All RLM group patients, and three non-RLM group patients had ipsilateral Horner's syndrome. RESULTS: Six of the RLM group had a ventilatory sensitivity to inhaled CO(2) (V/P(ET) CO(2)) below normal (group A: V/P(ET) CO(2), mean, 0.87; range 0.3-1.4 l. min(-1)/mm Hg). It was normal in all of the non-RLM group (group B: V/P(ET) CO(2), mean, 3.0; range, 2.6-3.9 min(-1)/mmHg). There was no significant difference in breathing between groups during relaxed wakefulness (V, group A: 7.44 (SD 2.5) l.min(-1); group B: 6.02 (SD 1.3) l.min(-1); P(ET) CO(2), group A: 41.0 (SD 4.2) mm g; group B: 38.3 (SD2.0) mm Hg) or during exercise (V/VO(2): group A: 21 (SD 6. 0) l.min(-1)/l.min(-1); group B: 24 (SD 7.3) l.min(-1)/l.min(-1)). During sleep, all group A had fragmented sleep compared with only one patient in group B (group A: arousals, range 13 to > 60 events/hour); moreover, in group A there was a high incidence of obstructive sleep apnoea associated with hypoxaemia. CONCLUSION: Patients with unilateral RLM lesions require monitoring during sleep to diagnose any sleep apnoea. The finding that unilateral RLM lesions reduce ventilatory sensitivity to inhaled CO(2) is consistent with animal studies. The reduced chemosensitivity had a minimal effect on breathing awake at rest or during exercise.

Adult↗
PubMed1999

Epilepsy in women: the science of why it is special.

Epilepsy is a common neurological disorder that may be affected by reproductive hormones and may complicate reproductive health. Many women with epilepsy experience changes in seizure frequency and severity with changes in reproductive cycles, including at puberty, over the menstrual cycle, with pregnancy and at menopause. Ovarian steroids alter neuronal excitability at the membrane and in the genome. Altered protein synthesis as a consequence of changes in RNA mediated gene transcription is one mechanism for steroid mediated effects on excitability. These genomic effects are delayed and sustained. In contrast, membrane effects are immediate and short duration. These effects are mediated at both the GABA-A and NMDA receptors. Estrogen also dynamically alters synaptic connectivity. Estrogen enhances excitability and lowers the seizure threshold, whereas progesterone enhances inhibition and increases the seizure threshold. In experimental models of epilepsy, estrogen is proconvulsant and progesterone is anticonvulsant. The net effect of these steroid actions is to alter neuronal excitability over physiological cycles. Some epilepsy syndromes are expressed or worsened at puberty. One third to one half of women with epilepsy have catamenial seizure patterns, with seizures most likely to occur in the perimenstrual period and at ovulation. More research is needed to understand the effects of menopause on epilepsy. Antiepileptic drugs may exacerbate the risk of reproductive endocrine disorders in women with epilepsy. Fertility rates are lower for women with epilepsy. Women with epilepsy are more likely to have anovulatory menstrual cycles, abnormal pituitary LH release and altered ovarian steroid concentrations. Polycystic ovaries are detected more often in women with epilepsy, particularly those on valproate. Treatment of hormone sensitive seizures relies on standard AEDs. Small trials suggest that adjunctive progesterone therapy is sometimes helpful. The newer AEDs, gabapentin and lamotrigine may have some advantages for women with epilepsy. These drugs do not alter levels of steroid hormones and do not interfere with effectiveness of hormonal contraception. Experience in pregnancy is limited. The dynamic effects of hormones on seizure expression and of seizures on reproductive health complicate the management of epilepsy in women. Newer AEDs may offer advantages for women with epilepsy in the reproductive years.

Epilepsy↗
PubMed1998

Effects of epilepsy on women's reproductive health.

Reproductive dysfunctions are common and wide-ranging in women with epilepsy. Menstrual cycle disruption, anovulatory cycles, disturbances in hypothalamic and/or pituitary hormones, and disturbances in gonadal steroids are more common among women with epilepsy. Sexual dysfunction can present as either disorders of desire or physiologic arousal, but the most common dysfunction appears to be an inadequate initial physiologic arousal response. Reproductive dysfunctions may be due to psychologic, pharmacologic, or physiologic factors. Physicians should routinely question all women with epilepsy regarding their reproductive and sexual health. A full history, a complete physical, and laboratory evaluations with endocrinologic work-up should be performed in any woman who reports a reproductive dysfunction. Treatment and/or referral to a gynecologist or endocrinologist should be initiated as appropriate.

Anovulation↗
PubMed1998

Effects of NREM sleep on dynamic within-breath changes in upper airway patency in humans.

The purpose of our study was to compare inspiratory- and expiratory-related changes in retropalatal cross-sectional area (CSA) during wakefulness to those during non-rapid-eye-movement (NREM) sleep. We studied 18 subjects in whom the severity of sleep-disordered breathing varied. Relative changes in CSA were visualized by using fiber-optic endoscopy. For each breath analyzed (wakefulness n = 4-13; sleep n = 7-16), the CSA was measured at fixed points within inspiration and expiration (0, 25, 50, and 100% of the inspiratory and expiratory duration); these measurements were expressed as a percentage of the CSA that occurred at the start of inspiration. During wakefulness, there was a statistically significant increase in the retropalatal CSA (compared with the start of inspiration) only during early expiration (group mean: expiration, 0% = 112.6 +/- 3.2 (SE) %; 25% = 122.8 +/- 6.2%; 50% = 110.6 +/- 3.8%). In contrast, during sleep, significant changes in CSA occurred during both inspiration and expiration (group mean: inspiration, 25% = 75.3 +/- 6.0%; 50% = 66.7 +/- 7.7%; 75% = 64.6 +/- 8.1%; expiration, 0% = 126.8 +/- 11.8%; 25% = 125.3 +/- 6.9%). The expiratory-related increase in CSA was followed by narrowing such that at end expiration the caliber of the airway was returned to that occurring at the beginning of inspiration (group mean at end expiration = 98.6 +/- 3.1%). The largest changes in CSA occurred in the subjects with an increased body mass index (BMI). We conclude that, during NREM sleep, significant changes in CSA occur during both inspiration and expiration and that the magnitude of these changes is significantly influenced by BMI.

Adult↗