Syntactic language processing: ERP lesion data on the role of the basal ganglia.

The role of the basal ganglia in syntactic language processing was investigated with event-related brain potentials in fourteen neurologically impaired patients. Seven of these patients had basal ganglia lesions while 7 other patients primarily had lesions of the left temporo-parietal region excluding the basal ganglia. All patients listened to sentences that were either correct or included a verb argument structure violation. In previous experiments this type of violation elicited a biphasic pattern of an N400-P600 complex in young healthy participants. While the N400 may result from incorrect semantic-thematic role assignment, the P600 reflects the fact that verb information does not license the syntactic structure at present. Results of the patient experiment revealed a double dissociation: patients with left temporo-parietal lesions only show a P600, whereas patients with lesions of the basal ganglia showed no P600, but a negativity with extended duration that resembled an N400. The latter pattern not only confirms previous reports that the basal ganglia modulate the P600 but extends these results by showing that the N400 as a late semantic-thematic integration process appears partially modulated by the basal ganglia.     

Inhibition of rat hippocampal excitability by the plant alkaloid 3-acetylaconitine mediated by interaction with voltage-dependent sodium channels

The effects of the Aconitum alkaloid 3-acetylaconitine on neuronal activity were investigated in the slice preparation and on cultivated neurons of rat hippocampus by extracellular and patch-clamp recordings, respectively. 3-Acetylaconitine (0.01–1 μM) diminished the orthodromic and antidromic population spike in a concentration-dependent manner. The inhibitory action of the drug was preceded by a transiently enhanced excitability. The latency of onset of the inhibition was accelerated by increased stimulation frequency, whereas recovery during washout of the alkaloid was accelerated by decreased stimulation frequency. Moreover, the inhibitory effect of 3-acetylaconitine was evaluated in two different models of epileptiform activity induced either by blockade of GABA receptors by bicuculline (10 μM) or by a nominal Mg²⁺-free bathing medium. In accordance with the activity-dependent mode of action, this compound abolished the synaptically evoked population spikes in the presence of bicuculline or nominal Mg²⁺-free bathing medium, respectively. Whole-cell patch-clamp recordings revealed an interaction of 3-acetylaconitine with the voltage-dependent sodium channel. At a concentration of 1 μM, 3-acetylaconitine did not affect the peak amplitude of the sodium current, but shifted the current-voltage relationship in the hyperpolarized direction such that sodium currents were already activated at the resting potential. Received: 22 July 1996 / Accepted: 14 October 1996     

Estradiol and tryptophan depletion interact to modulate cognition in menopausal women.

Despite an abundance of data in animals, there is little research in humans regarding how estrogen and serotonin (5-HT) may interact to influence cognition. Through the use of estrogen treatment (ET) and tryptophan depletion (TRP-D) in a within-subject design involving healthy menopausal women, we have manipulated both estrogen and 5-HT in order to evaluate their individual and joint effects. Although neither manipulation influenced visuospatial learning, a significant interaction suggested that estrogen exerted a protective effect on verbal memory, such that TRP-D impaired performance to a greater extent before the administration of ET. In consonance with this finding, ET was associated with a small, but positive mood effect on the day following active TRP-D. In addition, ET significantly improved letter-cued verbal fluency with and without TRP-D. Finally, time since last menstrual period was significantly associated with verbal memory scores, such that longer length of hypogonadism resulted in decreased verbal memory performance. These data support the interaction of estrogen and 5-HT in nonreproductive behavior in humans as well as highlight the role of ovarian steroids in cognition.     

p53 and skin carcinomas with skull base invasion: a case-control study.

BACKGROUND: Some skin carcinomas may be very aggressive. Increased expression of the protein p53 has been associated with tumor aggressiveness. In this study, p53 expression was evaluated in basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) with skull base invasion, and was compared to tumors with good outcome. STUDY DESIGN AND SETTING: Expression of p53 was immunohistochemically analyzed and it was reported as present or absent in 24 BCC and 11 SCC with skull base invasion. Control group (good outcome) included 23 BCC and 10 SCC. RESULTS: Expression of p53 was noted in 70.83% of BCC with skull base invasion, compared to 43.48% in the control group (P = 0.058). Regarding SCC, p53 positivity was noted in only 9.09% of SCC with skull base invasion, compared to 40.00% in the control group (P = 0.149). CONCLUSIONS: In this study, p53 expression was more common among BCC with skull base invasion, compared to controls with good outcome, and the difference was considered marginally significant. This proportion was reversed in SCC, but the difference was not statistically significant. EBM rating: B-3b.     

Lambert-Eaton myasthenic syndrome IgG depletes presynaptic membrane active zone particles by antigenic modulation

The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease that can be transmitted from human to mouse with immunoglobulin G (IgG). Electrophysiological studies indicate that LEMS IgG acts on presynaptic voltage-sensitive calcium channels, probably reducing their number, and freeze-fracture electron microscopy demonstrates that LEMS IgG has an effect on the presynaptic active zone particles, which represent putative voltage-sensitive calcium channels. The active zone particles, normally arranged in double parallel rows, move closer together, form clusters, and are reduced in number. The morphological data suggest modulation of the active zone particles crosslinked by LEMS IgG. If this were the case, then only divalent LEMS IgG and F(ab')2 should alter the deployment of active zone particles and monovalent Fab should be without effect. To test this hypothesis, mouse diaphragms were exposed to control and LEMS IgG and IgG fragments in organ culture for 24 hours and then studied by quantitative freeze-fracture electron microscopy. Divalent LEMS IgG and F(ab')2 aggregated and depleted the active zone particles, whereas monovalent Fab had no effect. The findings reconfirm that the active zone particles are targets of LEMS IgG and are direct evidence for modulation of the particles by LEMS IgG. The findings are in harmony with parallel electrophysiological studies of the effects of LEMS IgG fragments on transmitter release in the same diaphragm muscles (Lang et al, J Physiol 1987;390:173P).     

Antiemetic care for patients with breast cancer: focus on drug interactions and safety concerns.

PURPOSE: The drug interactions and adverse events that should be considered when individualizing antiemetic therapy for patients undergoing treatment for breast cancer are reviewed. SUMMARY: A variety of antiemetic agents are available, including antihistamines, dopamine-receptor antagonists, serotonin-receptor antagonists, and neurokinin-receptor antagonists. To ensure optimal symptom control for each patient without unnecessarily prolonging treatment, patient- and treatment-specific risk factors must be considered. Neurokinin-receptor antagonists, the newest class of antiemetics, are effective in preventing acute and delayed chemotherapy-induced nausea and vomiting but must be used in combination with a serotonin-receptor antagonist and a corticosteroid. The serotonin-receptor antagonists have become the mainstay of antiemetic therapy, but current guidelines do not distinguish among the different agents in this class. However, there are distinct pharmacologic differences that may affect the potential for drug interactions and, ultimately, patient outcomes and the occurrence of adverse events. Therefore, the potential for drug interactions must be considered when selecting an antiemetic, particularly for patients who are taking multiple concomitant medications. Further, because a number of breast cancer therapies and some antiemetic agents carry cardiovascular warnings or precautions and since breast cancer patients may already be suffering from cardiovascular complications, the possible cardiotoxic effects of the antiemetic or chemotherapy agents or the combinations of these agents should be considered. CONCLUSION: Antiemetic treatment is essential for patients with breast cancer who are undergoing moderately to highly emetogenic cytotoxic treatment. When selecting an antiemetic, clinicians must select an agent that provides optimal protection against nausea and vomiting while avoiding drug-drug interactions and additional adverse events.     

Artifacts due to stimulus correlated motion in functional imaging of the brain

To assess the effect of stimulus correlated motion on the appearance of functional magnetic resonance images, conventional visual and motor protocols were each performed by four normal volunteers and an image co-registration technique was used to retrospectively monitor subject motion. In three studies synthetic data sets were constructed from single baseline images using the positional information obtained from the co-registration procedure. Cumulative difference images were then created from both the synthetic and functional image sets. Stimulus correlated motion was detected in all eight studies and the synthetic cumulative difference images showed striking similarities to the equivalent functional images in each case.     

Relationship between Mandarin speech reception thresholds and pure-tone thresholds in the geriatric population.

BACKGROUND/PURPOSE: In the geriatric population, the reliability of pure-tone threshold (PTT) is sometimes poorer than that in young adults because of various reasons. This study assessed the relationship between Mandarin speech reception thresholds (SRTs) and PTTs in the aged and developed SRT as a measure for corroborating PTT. METHODS: This prospective study enrolled 46 consecutive subjects over 60 years of age. The results of SRT and PTT were collected from one ear randomly selected from each subject. Simple linear and multiple regressions were used to determine the correlation and linear regression coefficients between SRTs and PTTs at various frequencies. RESULTS: In the simple regression analysis, the correlation coefficient was highest at 1000 Hz (r = 0.949) and 500 Hz (r = 0.922), followed by 250 Hz (r = 0.850) and 2000 Hz (r = 0.792). In the multiple regression model with SRT as the dependent variable and PTTs as predictor variables, the resultant multiple correlation coefficient R was 0.967, while R2 was 0.936. In this model, PTTs at the frequencies of 500 Hz and 1000 Hz contributed significantly to the variance in SRTs with p values of 0.029 and < 0.001, respectively. These results demonstrated that the Mandarin SRT is strongly associated with PTTs at the frequencies of 500 Hz and 1000 Hz. CONCLUSION: This study established the agreement between Mandarin SRTs and PTTs in the low tone area of speech frequencies in the geriatric population. In clinical settings, SRT test can be rapidly and easily performed and is relatively inexpensive. It is a vital indicator of the accuracy of PTT measurement.