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Biomedical subjects

M L Wagner

Publications and source records attributed to M L Wagner.

At least 37 records · Page 2Linked to original sources

The relationship of tinnitus to craniocervical mandibular disorders.

Patients with craniocervical mandibular (TMD) disorders can present with tinnitus as a primary or secondary complaint. The embryology and functional anatomy of the middle ear, temporomandibular joint, muscles of mastication and associated tendons, ligaments, blood vessels, nerves and lymphatics was found to be helpful in establishing etiologic concepts which relate tinnitus to these temporomandibular disorders. In addition to etiologic concepts, treatment modalities are described. The authors relate their experiences as well as those of others with different patient populations.

Female↗

Riluzole: a new agent for amyotrophic lateral sclerosis.

OBJECTIVE: To provide a comprehensive review of riluzole, including its mechanism of action, pharmacokinetics, adverse drug reactions, drug interactions, efficacy, and administration. A brief review of amyotrophic lateral sclerosis (ALS) is also included. DATA SOURCES: A computerized search of the MEDLINE database in May 1996 was used to identify publications regarding ALS, riluzole, and metabolism by CYP1A2. Manufacturer's information on riluzole was used when there was no primary literature. DATA SYNTHESIS: Riluzole is approximately 90% absorbed following an oral dose. Its bioavailability is 60%. Peak concentrations occur within 1-1.5 hours of administration. Riluzole extensively binds to lipoproteins and albumin. This agent primarily undergoes CYP1A2 hydroxylation and glucuronidation, after which it is eliminated by the kidneys. Clearance is reduced in native Japanese healthy subjects and may be reduced in patients with hepatic impairment. Two trials with a total of 1114 patients addressed the efficacy of riluzole in ALS. Riluzole extended the time to tracheostomy or death, and the effect was greatest with dosages of 100 mg/d or greater. No effect on patients' symptoms or global assessment was detected at 18 or 21 months. Several flaws in these trials have led to questions concerning the validity of these results. The most commonly reported adverse effects of riluzole have been transient elevation of liver enzyme concentrations (2-5 times the upper limit of normal), worsening of asthenia, nausea, vomiting, diarrhea, anorexia, dizziness, vertigo, somnolence, and mouth paresthesia. Not as commonly reported, but still very serious, is neutropenia, which occurred in 3 of 4000 patients. CONCLUSIONS: Although the benefits of riluzole are questionable and it is expensive, this agent may extend the time to tracheostomy or death in patients with ALS. At present, this is the only agent approved for the treatment of ALS and should be made available for these patients.

Amyotrophic Lateral Sclerosis↗

"Subclinical" orthostatic hypotension is associated with dizziness in elderly patients with Parkinson disease.

OBJECTIVE: To investigate risk factors associated with subjective complaints of dizziness in 12 elderly patients with Parkinson disease (PD), in whom no obvious cause for this symptom could be found. DESIGN: A case-controlled study, with patients prospectively recruited in a nonblinded fashion. SETTING: Patients were seen by one physician at a neurology outpatient clinic between August 1993 and August 1994. SUBJECTS: Thirty-six patients, all over age 65 years and all with PD; 12 complained of dizziness; 24 did not. INTERVENTIONS: Patients and controls were screened for blood pressure changes, postural instability, motor severity, multiple sensory deficits, drug use, cardiovascular disease, and diabetes mellitus. MAIN OUTCOME MEASURES: An orthostatic decrease of systolic BP > 15 mmHg (odds ratio = 6.5; 95% confidence interval = 1.22 - 34.52; chi 2mh = 6.7; p < .01) and an orthostatic decrease of diastolic BP > 5mmHg (odds ratio = 11; 95% confidence interval = 3.15 - 38.39; chi 2mh = 7.14; p < .01) were significant risk factors for complaints of dizziness. RESULTS: The only significant risk factors linked with dizziness were orthostatic decreases in systolic (15 mmHg) and diastolic (5 mmHg) blood pressure. CONCLUSIONS: An orthostatic decrease in blood pressure is associated with unexplained feelings of dizziness in elderly PD patients.

Aged↗

Randomized, Double-Blind, Placebo-Controlled Study of Clonidine in Restless Legs Syndrome.

Ten patients with idiopathic restless leg syndrome (RLS) were asked to rate their symptoms at baseline during 2 weeks of placebo and 2 weeks of clonidine treatment by using a four-point scale. On two consecutive nights of each treatment period, polysomnography (PSG) and actigraphic studies were performed. Patients subjectively reported improvement in leg sensations (p = 0.02) and motor restlessness (p = 0.001) while receiving clonidine (mean = 0.5 mg/day). On PSG testing, sleep onset occurred faster with clonidine (12 minutes) compared with placebo (30 minutes) and baseline (47 minutes) (p = 0.006). Adverse findings associated with clonidine treatment included decreased percent REM sleep in the clonidine group (4%) compared with placebo (16%) and baseline (16%) (p = 0.001) and increased REM latency in the clonidine group (195 minutes) compared to the placebo (70 minutes) and baseline groups (89 minutes) (p = 0.028). There were no significant changes in total sleep time, stage 1 and 2 sleep, sleep efficiency, awakenings, arousals or periodic limb movements in sleep. There was a nonstatistical trend toward and increase in stage 3 and 4 sleep and a decrease in motor activity as measured by actigraphic recordings. Globally, seven out of 10 patients felt clonidine was more effective than placebo. Four patients chose to continue clonidine after the study. Clonidine may be an effective treatment for RLS patients who don't have large numbers of sleep-disrupting periodic limb movements but have delayed sleep onset due to leg sensations and subsequent motor restlessness.

Adrenergic Agonists↗

Clozapine for the treatment of psychosis in Parkinson's disease: chart review of 49 patients.

The records of 49 patients with Parkinson's disease and psychosis who were treated with clozapine for up to 18 months were reviewed. Average starting dose of clozapine was 16 mg. Average maximum dose was 39 mg. The psychotic symptoms improved in 76% of the patients at 3 months, and response to clozapine within the first year ranged from 71% to 80%. This response allowed a maximization of levodopa dose. Improvements in scores on the Unified Parkinson's Disease Rating Scale and tremor subscale were seen in some patients but were not statistically significant. This study, the largest of its kind to date, suggests that clozapine is well tolerated and effective in treating psychosis in patients with Parkinson's disease.

Aged↗

Current developments in neurology, Part I: Advances in the pharmacotherapy of headache, epilepsy, and multiple sclerosis.

When caring for patients with disorders of the central nervous system such as migraine headaches, epilepsy, or MS, clinicians are faced with increasingly complex pharmacotherapeutic options. Pharmacotherapeutic strategies directed toward prevention, reversal, or cure of these diseases are hampered by an incomplete understanding of the underlying pathophysiology. In this decade of the brain, basic science research combined with difficult but necessary clinical trials may answer some seemingly overwhelming questions for these devastating illnesses.

Adjuvants, Immunologic↗

Current developments in neurology, Part II: Advances in the pharmacotherapy of Alzheimer disease, Parkinson's disease, and stroke.

Disorders of the central nervous system provide innumerable challenges to the clinician. Often the underlying pathophysiology is not completely understood, thus preventing the design of treatment strategies aimed at correcting the underlying process. In this decade of the brain, basic science research combined with difficult but necessary clinical trials may answer some of these seemingly over-whelming questions for these devastating illnesses.

Alzheimer Disease↗

Severe mid-cervical kyphosis with cord compression in Larsen's syndrome and diastrophic dysplasia: unrelated syndromes with similar radiologic findings and neurosurgical implications.

Mid-cervical kyphosis in diastrophic dysplasia (DD) with cord compression and weakness has been recognized for the last three decades. A strikingly similar situation exists in Larsen's syndrome (LS), an otherwise unrelated problem of weakness with lay joints and dislocations with typical facies. Forty patients with DD were studied of whom seven had cervical spine kyphosis: one patient had spontaneous correction over the ensuing two decades. Seven patients with LS were studied of whom four had cervical spine changes with cord compression. There was one sudden death among the patients with LS and no cases of spontaneous correction. Muscle weakness in DD and LS should lead to evaluation of cervical spine kyphosis with cord compression. Plain films, CT and recently MRI are useful.

Cervical Vertebrae↗

Apomorphine for motor fluctuations and freezing in Parkinson's disease.

OBJECTIVE: To review the pharmacokinetics and use of apomorphine in patients with Parkinson's disease; to report a case of beneficial outcome with apomorphine in a patient with Parkinson's disease with severe levodopa "on-off" fluctuations and freezing; and to outline the types of patients or situations where apomorphine may be useful. DATA SOURCES: Case reports, review articles, and relevant clinical studies identified by a MEDLINE search of the English-language literature published between 1975 and October 1994. STUDY SELECTION: Because all but 2 reports were of open-label design with small sample sizes, all studies identified were evaluated. DATA EXTRACTION: The following data were extracted from each study: apomorphine treatment duration, dosing, onset, duration, and adverse effects. The following efficacy variables were extracted: percent decrease in off periods, improvement in parkinsonian symptoms, and percent decrease in levodopa dosage. DATA SYNTHESIS: Efficacy of apomorphine following subcutaneous, rectal, sublingual, and intranasal dosage forms are evaluated. We also describe the use of apomorphine in a patient with Parkinson's disease who experienced on-off fluctuations and freezing. Based on these reports, recommendations for patient selection, product selection, and apomorphine dosing guidelines are presented. CONCLUSIONS: Apomorphine decreases off time, freezing, and levodopa requirements in patients with Parkinson's disease. It can be administered via a number of different nonoral routes; however, subcutaneous apomorphine is the most extensively studied. Rectal, sublingual, and intranasal routes also have been shown to provide benefit in motor fluctuations, but differ from the subcutaneous route in onset of action, duration of effect, and adverse effect profile.

Administration, Intranasal↗

Clozapine therapy for Parkinson's disease and other movement disorders.

Recent research on the role of clozapine in the treatment of Parkinson's disease and other movement disorders is discussed. Most clinical trials have shown resolution of or improvement in psychotic symptoms accompanying Parkinson's disease without worsening of parkinsonian symptoms. Adverse effects appear to be mild at dosages of < 100 mg/day; sedation is the most frequent problem. Most of these studies have serious limitations, however; until better studies have been completed, the decision to use clozapine for Parkinson's disease-related psychosis should be made on a case-by-case basis, with thorough evaluation of risks, benefits, and other therapeutic options. Some patients with Parkinson's disease have shown improvement in tremor and other abnormal movements when given clozapine. Clozapine cannot be recommended for treating tardive dyskinesia on the basis of the research done so far; some trials show dramatic resolution of symptoms, others no benefit. Anticholinergics or dopamine-reuptake inhibitors should be considered before clozapine is given to patients with tardive dyskinesia because of clozapine's potential for serious adverse effects. A few patients with Huntington's disease have responded to clozapine, but again no conclusions can be drawn. Clozapine appears to offer no real advantage over haloperidol for treating choreiform movements in Huntington's disease. The frequency of tics in Tourette's syndrome does not seem to be reduced by clozapine. Clozapine has shown some efficacy as a treatment for psychosis and abnormal movements in Parkinson's disease. Results have been less promising for other movement disorders. Further study in larger populations is needed before any definitive conclusions about clozapine's place in movement disorder therapy can be made.

Clinical Trials as Topic↗

Felbamate: a new antiepileptic drug.

The chemistry, pharmacology, pharmacokinetics, clinical use, adverse effects, drug interactions, and dosage of felbamate are discussed. Felbamate (2-phenyl-1,3-propanediol dicarbamate) is chemically unrelated to any of the other currently marketed antiepileptic drugs (AEDs). It appears that felbamate, like phenobarbital and valproic acid, decreases the frequency of seizures by decreasing seizure spread and increasing seizure threshold. Oral felbamate is at least 90% absorbed, and peak concentrations are reached in one to six hours. The half-life is a little less than one day. A therapeutic range of plasma concentrations has not been determined. Felbamate has been used effectively as monotherapy and adjunctive therapy in patients with partial seizures with or without secondary generalization and as adjunctive therapy in children with partial or generalized seizures associated with Lennox-Gastaut syndrome. Felbamate may also be safe and effective in patients with generalized, absence, atypical absence, juvenile myoclonic, infantile, and gelastic seizures. The most frequently reported adverse effects of felbamate include nausea, anorexia, vomiting, headache, fatigue, somnolence, insomnia, and increased serum aspartate aminotransferase levels. The frequency of adverse effects is greater in patients receiving other AEDs in addition to felbamate. Felbamate affects the pharmacokinetics of phenytoin, carbamazepine, valproic acid, and methsuximide; other AEDs also affect the pharmacokinetics of felbamate. The dosage of felbamate should begin at 400 mg orally three times daily and then increase by 600 mg/day every two weeks to up to 3600 mg/day. If the patient is receiving other AEDs concurrently, their dosage should be decreased as the dosage of felbamate is increased. If the goal is to switch to felbamate, the dosage should be increased weekly as the dosages of other AEDs are reduced. Felbamate offers a safe and effective alternative to other AEDs in the treatment of partial and secondarily generalized seizures; partial and generalized seizures associated with Lennox-Gastaut syndrome; and atypical absence seizures, gelastic seizures, and other difficult to control seizures.

Anticonvulsants↗

Restless legs syndrome in childhood and adolescence.

Restless legs syndrome (RLS) is believed to be a condition primarily of middle to older age. However, it can have its onset in childhood. Five illustrative case histories with an autosomal dominant mode of inheritance are described. A mother and her 3 children (age: 6 1/2, 4 and 1 1/2 years) as well as a 16-year-old patient from a second family have typical RLS signs of leg discomfort (paresthesias) and motor restlessness prevalent at night and at rest, with temporary relief by activity. Polysomnography or videotaping revealed periodic limb movements in sleep (PLMS) and, in some cases, involuntary jerking of the legs was present during wakefulness as well. Clinicians should be aware that RLS can occur in childhood and adolescence and may be more common than heretofore recognized. "Growing pains" and attention deficit hyperactivity disorder (ADHD) are in the differential diagnosis of RLS in childhood.

Adolescent↗

The effect of felbamate on valproic acid disposition.

INTRODUCTION: Felbamate is a new antiepileptic drug approved for partial and secondarily generalized seizures. DESIGN: Subjects with epilepsy (three men and seven women; age range, 20 to 39 years; weight range, 53 to 88 kg) who were previously stabilized with valproic acid, 9.5 to 31.7 mg/kg/day, received both 600 and 1200 mg felbamate twice a day in an open-label, randomized, crossover study. RESULTS: Coadministration of 1200 or 2400 mg felbamate increased the mean valproic acid area under the curve (from 802.2 to 1025.4 and 1235.9 mg/hr/ml, respectively), peak concentrations (from 86.1 to 115.1 and 133.4 mg/ml, respectively), and average steady-state concentrations (from 66.9 to 85.5 and 103.0 mg/ml, respectively). No changes were observed in valproic acid time to peak concentration or protein binding. Average steady-state felbamate concentrations were 34.7 mg/ml for 600 mg administered twice daily and 61.2 mg/ml for 1200 mg administered twice daily. CONCLUSION: When felbamate is added to a regimen of valproic acid, valproic acid doses may require reduction because coadministration of felbamate decreased steady-state valproic acid clearance (28% and 54%, respectively; p < 0.01).

Adult↗

New treatment for rectal impaction in children: an efficacy, comfort, and safety trial of the pulsed-irrigation enhanced-evacuation procedure.

To determine the efficacy, comfort, and safety of the pulsed-irrigation enhanced-evacuation (PIEE) procedure in children, we evaluated 27 procedures performed on 24 consecutive children, 16 boys and 8 girls, 4-15 years old (mean, 8.7), with chronic constipation, encopresis, and rectal impaction. Children with known heart, lung, and/or neurologic diseases were excluded. Temperature, pulse, respiratory rate, and blood pressure were obtained prior to, during, and immediately after the procedure. Abdominal radiographs were obtained before and after the procedure, and the degree of disimpaction was estimated by a single radiologist. Patients graded the discomfort of the procedure at the time of speculum insertion and every 15 min from 1 to 5: 1, painless; 2, mild discomfort; 3, moderate discomfort; 4, severe discomfort; 5, extremely painful. Serum sodium, potassium, chloride, and bicarbonate values were obtained before, immediately after, and 90 min after the procedure and compared by paired Student t analysis. A digital rectal examination confirmed rectal impaction prior to insertion of the speculum. One course of pulsed irrigations was performed, typically lasting 25-30 min. No significant changes in vital signs were found during or after the procedure. In 18 of 23 (78%) procedures, there was at least a 50% emptying of feces from the colon immediately after the procedure. Patients continued to empty their colon up to 12 h later; thus, the procedure effectively disimpacted all patients. In terms of comfort, patients graded the PIEE a 2.6 +/- 0.75 (range, 1-5). Speculum insertion was the most uncomfortable factor and received a 2.7. No child had any indication of water intoxication.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗