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Biomedical subjects

J H Potvin

Publications and source records attributed to J H Potvin.

At least 37 records · Page 2Linked to original sources
PubMed1992

Fluoxetine: a review of receptor and functional effects and their clinical implications.

Downregulation of serotonin 5-HT1 receptors is the most frequently reported central nervous system neural effect of subchronic exposure to fluoxetine in rodents. However, downregulation of these receptors has not been universally demonstrated. Effects of subchronic exposure on 5-HT2 receptors are mixed. Fluoxetine exposure appears to have no effect on cholinergic muscarinic receptors. Effects on beta-adrenergic receptors are controversial, as only one laboratory has reported downregulation. The majority of studies have failed to show an effect on beta-adrenergic-receptor-stimulated cAMP generation. Electrophysiologic studies support the concept that fluoxetine facilitates net serotonergic transmission through downregulation of presynaptic inhibitory autoreceptors. Data suggest that its subchronic specificity and selectivity distinguish fluoxetine from members of other classes of available antidepressants, making it a distinct therapeutic option.

Animals↗
PubMed1992

Fluoxetine: no association with suicidality in obsessive-compulsive disorder.

Since (a) obsessive-compulsive disorder (OCD) may involve serotonergic neural transmission abnormalities also though to be related to regulation of suicide and aggression, (b) comorbidity between OCD and depression is substantial, and (c) depression is a major risk factor for suicide, a comprehensive analysis of clinical trial data was undertaken to assess the potential association of fluoxetine, a serotonin uptake inhibitor, and suicidality (suicidal acts and ideation). Pooled data from clinical trials comparing fluoxetine (n = 266) and placebo (n = 89) in patients with DSM-IIIR OCD were analyzed retrospectively. No suicidal acts occurred during placebo lead-in or double-blind therapy. Mean Hamilton Depression Scale item 3 (suicide item) scores improved statistically significantly with fluoxetine compared with placebo. Worsening in suicidal ideation was statistically significantly more frequent with placebo than with fluoxetine. Emergence of substantial suicidal ideation (change in baseline item 3 score of 0 or 1 to 3 or 4) was numerically greater with placebo than with fluoxetine (3.6% vs. 1.7%; not statistically significant). The incidence of suicidality in fluoxetine-treated patients with OCD was low, compared favorably with rates in corresponding placebo-treated patients, and was well within the range of estimates in previous studies of patients with OCD. These controlled clinical trial results suggest no undue risk of suicidality in patients with OCD treated with fluoxetine.

Adult↗
PubMed1992

Fluoxetine: activating and sedating effects at multiple fixed doses.

Serotonin uptake inhibitors are generally considered activating antidepressants. To assess rates and temporal patterns of activation and sedation as well as dose-effect relationships, adverse event data were evaluated from a fixed-dose study comparing placebo and fluoxetine 5, 20, and 40 mg/day in the treatment of major depressive disorder (N = 363) and two fixed-dose studies pooled together comparing placebo and fluoxetine 20, 40, and 60 mg/day in the treatment of major depressive disorder (N = 746). The adverse events nervousness, anxiety, agitation, and insomnia were considered indicative of activation; somnolence and asthenia were considered indicative of sedation. Activation and sedation were both statistically significant (p less than or equal to 0.05) treatment-emergent phenomena, but dose-effect relationships differed. Activation rates were relatively stable between 5 and 40 mg/day, and then increased at 60 mg/day. Sedation rates increased linearly to 40 mg/day and then were comparable at 40 and 60 mg/day. Discontinuations for either phenomenon were uncommon. The temporal patterns of first occurrences and persistence of activation and sedation differed. First occurrences of activation peaked early and declined over time with all doses. First occurrences of sedation also peaked early with all doses, but there may have been greater variability in first occurrences of sedation over time with lower doses. Persistent occurrences of sedation may decline less over time than persistent occurrences of activation.

Adult↗
PubMed1992

Lack of association between fluoxetine and suicidality in bulimia nervosa.

BACKGROUND: The coincidence of major depressive disorder in bulimia nervosa ranges from 35% to 80%. Because of this comorbidity and because suicidality (suicidal acts and ideation) is an inherent part of depression, assessment of the risk of suicide in patients with bulimia nervosa is of considerable interest. METHOD: Data from United States Investigational New Drug double-blind, placebo-controlled fluoxetine clinical trials in bulimia nervosa were analyzed comprehensively to assess the potential association between fluoxetine treatment and suicidality in 785 patients with DSM-III-R bulimia nervosa. Patients were predominantly women (98%), aged 17 to 63 years; of the randomly assigned patients, 16.9% exhibited 17-item Hamilton Rating Scale for Depression (HAM-D) total scores of 17 or greater at baseline (range, 0-31). Incidence of suicidality was analyzed by the incidence difference method. RESULTS: No fatal suicidal acts occurred; 9 (1.15%) of 785 patients made nonfatal attempts; 24 (3.06%) experienced emergent (text-defined) suicidal ideation. No statistically significant increases in the incidence of suicidal acts or suicidal ideation were observed among fluoxetine-treated compared with placebo-treated patients. A smaller percentage of fluoxetine-treated (2.0%) than placebo-treated (3.8%) patients experienced emergence of substantial suicidal ideation (change in baseline HAM-D Item 3 [suicide item] score of 0 or 1 to 3 or 4 during therapy). A statistically significantly greater proportion of fluoxetine-treated than placebo-treated patients experienced improvement in suicidal ideation (decrease in HAM-D Item 3 score) from baseline to endpoint (p = .026). CONCLUSION: Analyses of the incidence of suicidal acts and suicidal ideation did not indicate an increased risk of suicidality in patients with bulimia nervosa treated with fluoxetine compared with those treated with placebo.

Adolescent↗
PubMed1990

Pattern analysis shows beneficial effect of fluoxetine treatment in mild depression.

In a multicentered study, 372 patients with mild major depressive disorder with a Hamilton Rating Scale for Depression (HAM-D) score of 15 to 19 were randomly assigned to 6 weeks of treatment with placebo or 20 mg, 40 mg, or 60 mg/day of fluoxetine. Patients were rated weekly for improvement and the appearance of side effects. Pattern analysis of treatment response showed more patients in the active drug treatment groups having a persistent or a delayed persistent response, the types of response specifically associated with active treatment. Analyses of mean changes in treatment measures showed little difference among treatment groups. This may be explained in part by different distributions in outcome, placebo patients having had a higher frequency of mild improvement with fewer negative and very positive outcomes. Response rate analyses favor the active treatments numerically, but only one of the comparisons is statistically significant. These findings suggest a specific role for fluoxetine treatment in mildly depressed patients who do not respond promptly or who respond inconsistently to nonspecific treatment.

Adult↗
PubMed1983

Multimodality evoked potentials and neurophysiological tests in multiple sclerosis. Effects of hyperthermia on test results.

Data on critical frequency of photic driving (CFPD), frequency following response (FFR), and visual, somatosensory (peroneal nerve), and brain-stem auditory evoked potentials (EPs) were obtained from 20 patients who had clinically definite multiple sclerosis and ten healthy normal subjects in a controlled, balanced study under normothermic and hyperthermic (+1 degrees C) conditions with a test-retest interval of one week. Normal subjects' test results showed no changes during hyperthermia. Patients' EP and CFPD data correlated well with history, clinical signs, and symptoms during both normothermia and hyperthermia. The FFR test data were equivocal and not fully analyzed. Data from the four other tests showed additional patient abnormalities during hyperthermia. Multimodality testing increased the number of patient abnormalities compared with single tests, and the number increased further during hyperthermia. Test-retest reproducibility was higher during hyperthermia.

Adult↗
PubMed1982

Parkinson's disease: Cogentin with Sinemet, a better response.

1. A randomized, placebo controlled, double-blind cross-over study was conducted to evaluate the clinical efficacy of the anticholinergic agent, benztropine mesylate (CogentinR) in 29 patients with mild to moderate, idiopathic Parkinson disease. 2. Patients were maintained on a stable, therapeutically optimal dosage and schedule of levadopa-carbidopa (Sinemet) throughout the study. 3. Both the neurologist's and the patient's global assessments of treatment efficacy indicated that Sinemet plus benztropine mesylate resulted in significantly greater improvement than Sinemet plus placebo. 4. Qualitative and quantitative evaluations of relevant neurologic functions showed small, but statistically significant improvements for rigidity, finger tapping speed and activities of daily living in patients during the Sinemet plus benztropine mesylate treatment period. 5. At the completion of the study 16 patients chose to continue taking benztropine mesylate as an adjuvant to Sinemet. 6. No important adverse side effects occurred during the study.

Aged↗
PubMed1982

Multimodality evoked potentials: clinical applications and assessment of utility.

Visual evoked potentials (VEP), brain stem auditory evoked potentials (BAEP), somatosensory evoked potential (SEP), and long latency event related potentials (ERP) have been used to assess various aspects of the central nervous system. Multimodality evoked potential (MEP) testing uses a combination of these tests in the same clinical setting. In the diagnosis of multiple sclerosis and in the diagnosis of brain death, MEP testing has been shown to be more effective than any one evoked potential test used alone. In head trauma, MEP testing is an effective means of localization and prognostication. There are potential uses for MEP testing in Parkinson's Disease and uremia.

Brain Death↗
PubMed1981

Decreased verbal memory associated with anticholinergic treatment in Parkinson's disease patients.

The effects of chronic administration of the anticholinergic agent, benztropine mesylate (CogentinTM), on specific verbal memory were investigated as part of a placebo-controlled randomized double-blind crossover study to determine the clinical efficiency of CogentinTM as an adjuvant therapy with SinemetTM in Parkinson's disease. Twenty-nine males with clinically definite idiopathic Parkinson's disease participated in the trial. They were tested for acquisition of new word lists, and on four other cognitive tests before, during, between, and after two 10-week trial periods when they received either increasing doses of CogentinTM (maximum 2 mg) or placebo while on a maintenance dose of SinemetTM. Patients showed a statistically significant decrease (5--10%) in word list acquisition while on CogentinTM. The anticholinergic memory effect was unrelated to the degree of improved clinical efficacy of CogentinTM for the Parkinsonism, and to initial word list acquisition ability. Verbal memory findings indicate that chronic administration of an anticholinergic in even low therapeutic dosage may play an important role in memory function.

Aged↗
PubMed1980

Multiple sclerosis de novo CNS IgG synthesis. Effect of CNS irradiation.

Megavoltage CNS irradiation was given to 20 patients with clinically definite multiple sclerosis (MS) to determine if de novo CNS IgG synthesis could be eradicated. In all five patients given 1,200 rads, a transient reduction in the de novo CNS IgG synthesis rate was noted. In ten patients given 1,800 rads, the following occurred: a reduction in synthesis rate in three patients, a reduction followed by enhancement in two, only enhancement in four, and no change in one. In all five additional patients, a therapy of adrenocorticotropic hormone (ACTH) followed by prednisone in combination with 1,800 rads produced greater and more persistent decreases in CNS IgG synthesis, but did not block the enhancement effect. Only two of 19 patients who had abnormal CNS IgG synthesis rates had reductions to normal; no patients showed changes in the number or pattern CSF IgG oligoclones. Hence, no treatment eradicated de novo CNS IgG synthesis. A persistent decrease in CSF leukocytes occurred in all 20 patients due to the reduction of small lymphocytes (not dose related). The blood-brain-barrier to albumin concentration was transiently damaged in 11 of 15 patients given irradiation, but when patients were premedicated with ACTH/prednisone therapy, no damage was found. None of the patients demonstrated neurological improvement, change in the activity of their disease, or persistent adverse effects.

Adrenocorticotropic Hormone↗
PubMed1980

Increased ratio of carbidopa to levodopa in treatment of Parkinson's disease.

A randomized, double-blind clinical trial was designed to compare two ratios of carbidopa to levodopa (10 mg of carbidopa to 100 mg of levodopa [Sinemet 10/100] and 20 mg of carbidopa to 100 mg of levodopa [Sinemet 20/100]) with levodopa (100 mg) alone. Twenty-nine male patients (46 to 78 years of age) with clinically definite idiopathic Parkinson's disease of mild to moderate severity were selected and hospitalized for the three-week period of the study. Medications being taken at time of entry were phased out during week 1. Fixed daily increments of medications were given during week 2, and adjusted during week 3 to achieve best clinical response with fewest side effects. Qualitative and quantitative examinations of neurologic function showed that upper extremity measurements of resting tremor, rigidity, and finger-tapping speed, and lower extremity measurements of foot coordination and tandem gait (both types of speed tests) showed significantly more improvement in patients receiving the 20:100 combination than in those receiving the 10:100 combination or levodopa alone. Adverse effects were similar and minimal in each of the three groups. Results indicate that increasing the amount of carbidopa from 10 to 20 mg per 100-mg dose of levodopa gives a greater therapeutic response in Parkinson's disease than does a 10:100 carbidopa-levodopa ratio or levodopa alone.

Aged↗
PubMed1980

Failure of intravenous and intrathecal cytarabine to modify central nervous system IgG synthesis in multiple sclerosis.

To study the nature of the multiple sclerosis (MS) central nervous system (CNS) immune reaction, cytarabine (ara-C) was administered intravenously to three patients and intrathecally to another seven. Although intravenous administration severely suppressed circulating leukocytes derived fom the bone marrow, there was no change in de novo CNS IgG synthesis (rate or presence of CSF IgG oligoclones). Therefore, the MS CNS immune reaction can persist in the presence of severe granulocytopenia and severe monocytopenia of one to two weeks' duration. In four patients who were given ara-C intrathecally, cytotoxic levels (> 10 micrograms/ml) were present for a least 24 hours. A brief elevation in CSF albumin indicated transient damage to the blood-brain barrier. Leukopenia did not result in the seven patients treated intrathecally, and de novo CNS IgG synthesis did not change or was transiently increased. Assuming that cytotoxic levels in CSF diffused to the CNS sites responsible for synthesizing IgG, results indicate that CNS IgG synthesis does not depend on in situ rapid turnover of immune cells. None of the ten patients demonstrated neurological improvement or persistent adverse effects.

Adult↗
PubMed1980

Human neurologic function and the aging process.

Sixty-one normal men whose ages ranged from 20 to 80 years were evaluated on two occasions by means of a comprehensive series of 128 instrumented tests of neurologic function. The tests measured cognition, vision, strength, steadiness, reactions, speed, coordination, fatigue, gait, station, sensations, and tasks of daily living. The reliability of each test measured was determined, and any measure found unreliable (r less than or equal to 0.41) was not further analyzed. Significant age-related linear decreases were found for almost all neurologic functions. The declines over the age span varied from less than 10 percent to more than 90 percent for different functions. For the upper extremities, the largest declines (greater than 50 percent) were in hand-force steadiness, speed of hand-arm movements, and vibration sense; for the lower extremities, the largest declines were in one-legged balance with eyes closed and in vibration sense. For 13 of 14 tests in which significant dominant body-side effects were found, larger re-testing 7-10 days later, the subjects improved their scores by more than 5 percent on only 17 tests, 9 of which concerned the activities of daily living. No significant differential learning effects were found across age groups. The results point to the importance of developing a data bank on age-based neurologic function so that therapeutic effects can be evaluated in terms of age- and sex-matched normal functioning.

Adult↗
PubMed1980

Multiple sclerosis de novo CNS IgG synthesis: effect of ACTH and corticosteroids.

ACTH gel and corticosteroids were given to 28 clinically definite multiple sclerosis (MS) patients to determine whether de novo central nervous system (CNS) IgG synthesis (rate and cerebrospinal fluid [CSF] IgG oligoclonal bands) could be eradicated. The most effective treatments were ACTH gel and ACTH gel followed by prednisone, all 11 patients had a significant reduction in rate (p < 0.05), which became normal in eight patients (< 3.3 mg per day). In order of effectiveness, the other drugs used were: dexamethasone or prednisone given orally, and hydrocortisone administered intrathecally. For most treatments, reduction of the rate of CNS IgG synthesis occurred within days and persisted for months after cessation of treatment. The MS CNS immune reaction was not eradicated when IgG synthesis rate became normal, because CSF IgG oligoclonal bands persisted. None of the chronic progressive, severely disabled patients demonstrated significant change in neurologic function or persistent adverse effects.

Adrenal Cortex Hormones↗
PubMed1980

Multiple sclerosis: measurement and validation of central nervous system IgG synthesis rate.

An empirical formula has been developed to calculate the de novo rate of synthesis of IgG in the central nervous system (CNS), based on physiologic principles that govern the passage of albumin and IgG across the blood-brain barrier (BBB). To validate the formula, radiolabeled IgG and albumin from pooled normal sera were followed from the blood to the cerebrospinal fluid (CSF) over 21 days in nine patients with definite multiple sclerosis (MS). IgG synthesis rates were calculated by the isotope exchange method and compared to values obtained with the empirical formula. There was excellent concordance, from a low rate of synthesis of 5 mg per day to a high rate of 120 mg per day. A double radiolabeled IgG experiment in two patients showed that the MS BBB processed normal serum IgG in the same way as IgG derived from autologous MS serum. Accordingly, the empirical formula, which requires only one sample of CSF and matched serum, can reliably and validly estimate the de novo rate of IgG synthesis in CNS of patients with MS.

Blood-Brain Barrier↗
PubMed1980

Speech sounds: evaluation of a device for their visual presentation.

Two experiments were designed to evaluate a prototype device developed to provide a visual presentation of speech sounds as a potential assistive device for hearing-imparied persons. In the 1st experiment, the ability of adults with unimpaired hearing to recognize the visual patterns of 3 vowels spoken by 3 different speakers was assessed, and in the 2nd experiment, visual and auditory distinctiveness of the 3 vowels was compared. Results showed that subjects received different speech information from the Visual Speech Spectrum Analyzer (VISSA) and the normal auditory system; however, differences were judged minor. The device has potential as a speech therapy aid and may prove helpful to hearing imparied persons.

Adult↗