Botulinum toxin A therapy in dystonia.
Local injections can decrease posturing and pain in 70% to 90% of patients for up to eight months. Responses can be extended with further injections.
Botulinum Toxins↗
Biomedical subjects
C H Adler
Publications and source records attributed to C H Adler.
Oculo-facial-skeletal myorhythmia in Whipple disease: treatment with ceftriaxone.
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Adult↗
Parkinsonism secondary to bilateral striatal fungal abscesses.
A 24-year-old man with an 11-year history of i.v. drug use rapidly developed parkinsonism clinically indistinguishable from MPTP toxicity and Parkinson's disease. Although tests were negative for the human immunodeficiency virus, radiologic evaluation revealed bilateral striatal lesions. Stereotactic biopsy demonstrated septate hyphae consistent with either aspergillosis or mucormycosis. Gradual improvement followed systemic therapy with amphotericin B.
Adult↗
Receptor reserve at the alpha-2 adrenergic receptor in the rat cerebral cortex.
N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an irreversible alpha-2 antagonist, was used to establish and quantitate the receptor reserve at the alpha-2 adrenergic autoreceptor mediating inhibition of [3H]norepinephrine ([3H]NE) release in rat cerebral cortical slices. EEDQ treatment had no effect on [3H]NE uptake or base-line release. Four hours after EEDQ treatment (0.8 mg/kg i.p.), the EC50 was shifted 7-fold to the right and there was a 21.5% decrease in the maximal response to the full alpha-2 agonist UK-14304. Using the double-reciprocal plot analysis, the equilibrium activation constant (KA) was calculated to be 1.41 +/- 0.8 microM. Similar analysis of alpha-2 autoreceptor response at various times after 1.6 mg/kg of EEDQ gave similar values for the KA. Therefore, evaluation of either the response of the remaining native receptors after partial irreversible inactivation or the response of newly synthesized receptors after nearly complete irreversible inactivation can be used to determine the KA of the receptor. Comparison of repopulation kinetics analyses for alpha-2 receptor response and estimated receptor number revealed that recovery of maximal response was much faster than actual receptor recovery. By examining the relationship between alpha-2 autoreceptor occupancy and response it was possible to determine that there is approximately a 60 to 70% receptor reserve; only 1.5% of the receptors need to be occupied by UK-14304 in order to obtain 50% of the maximal inhibition of [3H]NE release. The presence of a large receptor reserve must be taken into account when evaluating alpha-2 adrenergic autoreceptor regulation in the rat cerebral cortex.
Animals↗
Receptor reserve at striatal dopamine autoreceptors: implications for selectivity of dopamine agonists.
The dose response curve for apomorphine reversal of gamma-butyrolactone (GBL)-induced L-DOPA accumulation in rat striatum was shifted almost 6-fold to the right after partial irreversible blockade (83%) of dopamine (DA) autoreceptors with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ); however, the maximal response was not reduced. In contrast, the major effect of a similar degree of irreversible blockade (86%) on the dose-response curve for the autoreceptor-selective agent EMD 23,448 was a reduction in maximal response (60% of control), indicating that EMD 23,448 is a partial agonist. A large receptor reserve therefore exists at the DA autoreceptor, which may explain in part why many DA agonists are more potent in models pre- than postsynaptic receptor activation.
4-Butyrolactone↗
Recovery of alpha 2-adrenoceptor binding and function after irreversible inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ).
Treatment of rats with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) resulted in a pronounced loss of alpha 2-adrenoceptor binding ( [3H]RX-781094) and a marked reduction in the ability of the alpha 2-agonist UK-14,304 to inhibit K+-stimulated release of both [3H]NA and [3H]5-HT in cerebral cortex. Repopulation of alpha 2-adrenoceptors was monoexponential with a t1/2 of 4.1 days; functional recovery was also monoexponential, with t1/2 values of 2.4 and 4.6 days for restoration of alpha 2-mediated inhibition of [3H]NA and [3H]5-HT release, respectively. Other studies suggest the difference in functional recovery rate may reflect the presence of a large receptor reserve for autoreceptors relative to heteroreceptors.
Adrenergic alpha-Antagonists↗
Tolerance to morphine-induced mydriasis in the rat pupil.
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Animals↗
Morphine-induced mydriasis and fluctuation in the rat: time and dose relationships.
The purpose of this investigation was to establish complete dose- and time-response relationships of morphine action on the rat pupil using serial observations. Adult male, albino rats of the Sprague-Dawley strain were used. Pupil size was measured by a series of photographs taken every 60 sec for at least 90 min under dim red illumination. The pupil began to dilate within 20 min after s.c. administration of doses of morphine sulfate as low as 1 mg/kg. The dose-related mydriasis reached a maximum with a dose of 32 mg/kg at 35 to 50 min after injection and lasted for 3 to 4 hr. The mydriasis was characterized by a rapid and marked fluctuation which was also dose-related and reached a peak with 32 mg/kg of morphine sulfate. Naloxone HCl (1 mg/kg) rapidly reversed both the mydriasis and the oscillation, thereby implicating an opiate receptor-mediated mechanism. In addition to providing a convenient measure of narcotic actions, the pupil may offer a particularly useful means for studying opiate receptor mechanisms since it is one of the few cases where, in many species, the anatomical pathways and neurochemical innervations are known.
Animals↗
Toxicity to heavy metals and relationship to seizure thresholds.
The present study was designed to provide information on the effects of lead, mercury, and nickel on lethality, body weight, and brain excitability in the adult rat. Both short- (2 days) and long-term (6 wk) drug administrations were carried out in adult male albino rats (Sprague-Dawley, Zivic-Miller). Based on the mg/kg/day of drug given over a 2-day period, the LD50 values were as follows: Pb(Ac)2, 215; Pb(NO3)2, 65.9; MMC, 11.9; HgCl2, 4.5; Ni(Ac)2, 35-40; NiSO4, 35-40. High doses of each of the metals administered acutely caused a drop in body weight but had an inconsistent effect on flurothyl-induced seizure thresholds. Pb(Ac)2, 200 mg/kg/day for 2 days, produced a statistically significant anticonvulsant effect, while 50 mg/kg Pb(NO3)2 resulted in a fall in threshold. Both NiSO4 and Ni(Ac)2, 30 mg/kg, increased seizure threshold. Neither the organic nor inorganic mercury altered thresholds. Long-term administration of Pb(Ac)2, MMC, or HgCl2 resulted in marked effects on body weight but no significant change in brain excitability.
Animals↗
The effect of temperature on hand function in patients with tremor.
Hand therapists may notice a patient's tremor when treating another diagnostic problem, such as arthritis or a fracture. In these instances, the tremor may become apparent as the patient attempts to don or doff a splint or to practice a home exercise program, or it may be reported in terms of difficulty with dressing or eating. The authors hypothesized that limb cooling would temporarily improve hand function among patients with essential tremor (ET) and that limb warming would temporarily improve hand function among patients with resting tremor secondary to Parkinson disease (PD). Twenty patients with ET and 20 patients with PD completed this single-blind randomized crossover study. Scores following exposure to cold water were compared with scores following exposure to warm water. For patients with ET, subtest scores for the Archimedes spiral, simulated feeding, and checkers were, statistically, significantly lower (i.e., improved) following exposure to cold water than following exposure to warm water; scores for Archimedes spiral card turning, simulated feeding, and checkers were significantly lower following exposure to cold water than at baseline. Scores for Archimedes spiral and card turning were also significantly lower following exposure to warm water than at baseline. For patients with PD, no statistically significant differences were noted between treatments or from baseline except the score for small common objects, which was lower (improved) following exposure to warm water than at baseline. The significant findings from this study support the therapeutic use of cooling to temporarily decrease tremor, thereby improving hand function among patients with ET.
Aged↗
A pilot study on the motor effects of rimantadine in Parkinson's disease.
The purpose of this pilot study was to determine whether rimantadine, the alpha-methyl derivative of amantadine, might have any antiparkinsonian properties. In an open-label trial, 14 patients (12 de novo and 2 on levodopa treatment) with Hoehn and Yahr stage 2 to 3 Parkinson's disease were placed on rimantadine at doses of 100 to 300 mg/d. No patients had dyskinesias or motor fluctuations. Ten of 14 (71%) reported a mean subjective response of 33% (range 10%-60%) to rimantadine. After treatment, there was a 13% improvement in Hoehn and Yahr staging (p = .01) and a 20% improvement in mean motor Unified Parkinsons Disease Rating Scale scores (p = .02). Rigidity was the most consistently improved feature among the responders. Mean effective dose was 256 mg/d (range 200-300 mg/d). Side effects were mild and transient, with nausea being most common (4/14). We conclude that rimantadine has some motor benefits in Parkinson's disease. A double-blind placebo-controlled study is warranted to validate our findings.
Adult↗
A home diary to assess functional status in patients with Parkinson's disease with motor fluctuations and dyskinesia.
In clinical trials for patients with Parkinson's disease (PD) with motor fluctuations, efficacy is generally ascribed to an intervention if motor function is significantly improved or if "off" time is significantly reduced. However, we have argued that patients might not be improved if off time is reduced only to the extent that unwanted dyskinesia is increased. Therefore, a home diary should include an assessment of dyskinesia to provide an accurate reflection of clinical status over a period of time. We undertook two studies to develop a home diary to assess functional status in patients with PD with motor fluctuations and dyskinesia. In both studies, patients concurrently completed a test and a reference diary. In Study I, we evaluated the impact of different severities of dyskinesia on patient-defined functional status. There were 1,149 evaluable half-hour time periods from 24 patients; 94.3% of off time was considered "bad" time and 90.2% of "on" time without dyskinesia, 72.6% of on time with mild dyskinesia, 43.0% of on time with moderate dyskinesia, and 15.2% of on time with severe dyskinesia was considered "good" time. In Study II, we evaluated a new home diary designed to separate dyskinesia that had a negative impact on patient-defined functional status from dyskinesia that did not. There were 816 evaluable time periods from 17 patients; 84.9% of off time and 89.9% of on time with troublesome dyskinesia was considered bad time while 85.5% of on time without dyskinesia and 93.8% of on time with nontroublesome dyskinesia was considered good time. With this diary (Diary II), the effect of an intervention can be expressed as the change in off time and the change in on time with troublesome dyskinesia (bad time). The sum can be used as an outcome variable and compared to baseline or across groups. In evaluating the efficacy of an intervention, assessment of change in off time and change in on time with troublesome dyskinesia provides a more accurate reflection of clinical response than change in off time alone.
Aged↗
Biofeedback for writer's cramp.
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Biofeedback, Psychology↗