摘要:

SummaryOver the last several years, the therapeutic approach to bacterial meningitis has been changing. The neurological complications of bacterial meningitis result from an inflammatory process that is initiated by the lysis of bacteria in the subarachnoid space by antibiotics; to alter the pathophysiologic events initiated by this lysis, adjunctive therapy to antimicrobial therapy has been investigated in experimental and clinical trials. This article reviews our present understanding of bacterial meningitis, the efficacy of dexamethasone in treatment, and the potential use of leukocyte monoclonal antibodies, pentox-ifylline, nonsteroidal antiinflammatory agents, and anticytokine antibodies.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummarySelective serotonin reuptake inhibitors (SSRIs) are effective in alleviating the symptoms of depression. However, clinical improvement is only obtained after several weeks of treatment. SSRIs, when administered acutely to animals, have little effect on synaptic levels of serotonin. This suggests the existence of one or more regulatory mechanisms controlling serotonergic neurotransmission. The firing rate of dorsal raphe serotonergic neurons is under the control of somatodendritic 5-hydroxytryptamine1A (5-HT1A) autoreceptors, the release of serotonin from nerve terminals is under the control of 5-HT autoreceptors (5-HT1B subtype in rodents, 5-HT1D in other species), whereas the control of the activity of tryptophan hydroxylase, the rate-limiting enzyme of serotonin synthesis, is complex, involving 5-HT1A but possibly other 5-HT receptors including the 5-HT1B/D subtype. During prolonged administration with a SSRI, these three feedback systems become desensitized and their regulatory effects on serotonergic neurotransmission are weakened or lost. This has the effect of allowing the synaptic levels of serotonin to rise with a consequently increased stimulation of one or more types of postsynaptic 5-HT receptor. Thus, it is only after prolonged administration that the pharmacological activity of SSRI is fully expressed in terms of synaptic serotonin levels. This may explain the latency of antidepressant action seen with these drugs in humans. Various other classes of antidepressant therapies (tricyclic antide-pressants and monoamine oxidase inhibitor drugs, electroconvulsive therapy) have long-term effects on one or more of the feedback mechanisms such that an increase in synaptic concentrations of serotonin may be a common mechanism of many antidepressant therapies.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryPeripheral-type benzodiazepine receptors (PER) are prominent in peripheral organs, whereas in the brain, they are sparse and located mainly in glial cells. The PER bind with high affinity the ligands Ro 5–4864 (4'-chlorodiazepam) and PK 11195 (an isoquinoline carboxamide derivative), but not clonazepam, which binds with high affinity to central-type benzodiazepine receptors (CBR). Subcellularly, PER are predominantly localized on the outer mitochondrial membrane. It appears that the PER are composed of three sub-units: an 18-kDa subunit that binds isoquinoline carboxamide derivatives; a 30-kDa subunit that binds benzodiazepines; and a 32-kDa subunit labeled by the benzodiazepine [3H]AHN 086, the voltage-dependent anion channel. Recently, complementary DNA (cDNA) encoding for rat and human PER was isolated and sequenced. The PER gene is located in the q13.3 region of the long arm of human chromosome 22. The PER play a major role in steroidogenesis, controlling cholesterol mitochondrial transport. Diazepam-binding inhibitor and its processing products, as well as porphyrins, have been suggested as putative endogenous ligands for these receptors. The PER ligands have been shown to control cell proliferation and differentiation, and the binding capacity for these ligands is enhanced in some malignant tumors. Stress has been demonstrated to affect PER bidirectionally. Acute stress is associated with increased PER density, whereas chronic stress down-regulates PER.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryA group of four monkeys was rendered parkinsonian with the toxin MPTP. They were then treated chronically with L-DOPA/benserazide 50/12.5 mg/kg given orally daily for 2 months. This dose produced a striking antipar-kinsonian effect, but all animals manifested dyskinesia. A series of agents acting primarily on neurotransmitters other than dopamine were then tested in combination with L-DOPA to see if the dyskinetic movements would be modified. Several drugs, including clonidine, physostigmine, methysergide, 5-MDOT, propranolol, and MK-801, markedly reduced the dyskinetic movements but at the cost of a return of parkinsonian symptomatology. However, yohimbine and meperidine reduced predominantly the dyskinetic movements. Baclofen was also useful in one monkey against a more dystonic form of dyskinesia. Atropine converted the dystonic movements into chorea.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryTo define a mechanism for the pressor effects of thyrotropin-releasing hormone (TRH), we evaluated changes in mean blood pressure (MBP) when a synthetic form of TRH (0.1 mg/kg, i.v.) was injected into two types of comatose patients: vegetative and brain dead. The patients in the vegetative group (n = 7, age 58 ± 6) retained spontaneous respiration and brainstem function, whereas the brain-dead (BD) patients (n = 7, age 68 ± 4) lacked these functions. In the vegetative group, TRH caused significant increases in MBP (from 91 ± 8 mm Hg to 110 ± 10 mm Hg) at 2 min after the injection [p < 0.05, analysis of variance (ANOVA) with a Scheffe F-test]. In contrast, five of the seven BD patient showed no alterations in the measured parameter in response to the TRH injection. However, the remaining two BD patients, who had spinal reflexes, exhibited an elevation in MBP. In such BD patients, baroreceptor reflex function was virtually absent, suggesting that the blood pressure regulation mediating through the baroreceptor reflex system might be abolished. These results indicate that in comatose patients, the hemodynamic effects of TRH may differ depending on impairments in the central nervous system; the results support previous reports indicating a mediation of the central sympathetic nervous system in the development of pressor effects of TRH. Furthermore, because brain-dead patients with spinal reflexes showed hypertensive responses to TRH, there is a possibility that these responses may have resulted from an activation of TRH receptors in the spinal cord.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryWe assessed the short-term memory (STM) using the Visual Paired Associates and the Verbal Paired Associates test, and the motor status at the end of 7.8 ± 3.7 years of anticholinergic therapy in 22 nondemented patients with Parkinson's disease (PD). Eighteen patients managed to stop anticholinergic therapy. During anticholinergic therapy, STM in PD is significantly worse than in normal controls (CS). Two months after the withdrawal of anticholinergic drugs, the STM retest gain is significantly greater in PD than in CS, and at that time STM in PD did equal CS levels. After withdrawal of anticholinergic therapy, thirteen patients noticed a deterioration of motor function; the dose of levodopa had to be increased in seven patients. We conclude that in nondemented PD patients, long-term anticholinergic therapy probably does not result in irreversible damage to STM, and withdrawal of long-term anticholinergic therapy is feasible in the majority of PD patients.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryStriatal dynorphin system function may be altered in Parkinson's disease. To evaluate whether treatment with a selective dynorphin agonist improves motor symptoms, four parkinsonian patients received single daily injections of spiradoline under controlled conditions. Doses ranging from 1 to 4 μg/kg had no discernible effect on motor performance when given alone or in combination with levodopa-carbidopa. Three patients developed dose-limiting adverse effects, especially behavioral alterations. These results suggest that dynorphin replacement strategies, using spiradoline-like κ-1 agonists, may have limited value in the therapy of patients with Parkinson's disease.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryA 42-year-old man had suffered from Parkinson's disease for 5 years. Levodopa was effective, but the wearing-off phenomena were severe. Because of relatively low levels of serum copper and ceruloplasmin, D-penicillamine was administered. D-penicillamine increased plasma levodopa concentrations, thereby improving his parkinsonian symptoms. We propose that D-penicillamine facilitates levodopa absorption and, hence, the efficacy of the antiparkinsonian drug.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryAmong the side effects attributed to sodium valproate administration, the production of a parkinsonian syndrome is very uncommon, particularly in children. We report a 12-year-old girl with secondary epilepsy; 7 days after the initiation of valproate therapy she developed parkinsonism that disappeared completely when valproate was replaced by carbamazepine. We discuss the possible role of alterations in GABAergic neurotransmission in the extrapyramidal syndrome that developed.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

SummaryThe effects of nicardipine, a calcium channel blocker (CCB), were investigated in 11 patients with essential tremor (ET). In a placebo controlled study, a single oral dose of 30 mg of nicardipine was administered, followed by 1 month of sustained treatment (60 mg/day). Tremor was assessed by acceler-ometric recording. A single oral dose of nicardipine reduced the tremor amplitude respect baseline (p = 0.003) and placebo (p = 0.008). After 1 month of chronic treatment, nicardipine still reduced the tremor amplitude (30.78% ± 17.13 SE from baseline), but failed to sustain the initial statistical improvement. A single oral dose of nicardipine is effective in reducing ET.

ISSN:0362-5664    

出版商:OVID    

年代:1993

数据来源: OVID