The AMPA receptor potentiator LY404187 increases cerebral glucose utilization and c-fos expression in the rat.

AMPA receptor potentiators enhance AMPA receptor-mediated glutamatergic neurotransmission and may have therapeutic potential as cognitive enhancers or antidepressants. The anatomical basis for the action of AMPA receptor potentiators is unknown. The aim of this study was to determine the effects of the biarylpropylsulfonamide AMPA receptor potentiator, LY404187 (0.05 to 5 mg/kg subcutaneously), upon cerebral glucose utilization and c-fos expression using 14C-2-deoxglucose autoradiography and c-fos immunocytochemistry. LY404187 (0.5 mg/kg) produced significant elevations in glucose utilization in 28 of the 52 anatomical regions analyzed, which included rostral neocortical areas and the hippocampus, as well the dorsal raphe nucleus, lateral habenula, and locus coeruleus. No significant decreases in glucose utilization were observed in any region after LY404187 administration. The increases in glucose utilization with LY404187 (0.5 mg/kg) were blocked by pretreatment with the AMPA receptor antagonist LY293558 (25 mg/kg), indicating that LY404187 acts through AMPA receptor-mediated mechanisms. LY404187 (0.5 mg/kg) also produced increases in c-fos immunoreactivity in the cortex, locus coeruleus, and the dorsal raphe nucleus. These studies demonstrate neuronal activation in key brain areas that are associated with memory processes and thus provide an anatomical basis for the cognitive enhancing effects of AMPA receptor potentiators.     

Improvement in depressive illness is not associated with altered release of neurophysins over a course of ECT

The hypothesis that the release of vasopressin-associated neurophysin (hNpI) or oxytocin-associated neurophysin (hNpII) is modified by a course of electroconvulsive therapy (ECT) was tested by the measurement of serum neurophysins before and after the first and last ECTs given to 17 unipolar depressed patients. Neither basal nor ECT-induced neurophysin release changed between the first and last ECTs. Data from the present study were combined with data from a previous published study to provide a sample of 29 unipolar depressed patients. In this extended sample, the release of hNpII after the first ECT was significantly correlated with improvement in symptoms of depression over a course of ECT as measured by the Hamilton Rating Scale for Depression and the Montgomery-Asberg Depression Rating Scale.     

Health status measurement in Parkinson's disease: validity of the PDQ-39 and Nottingham Health Profile.

We assessed the feasibility and psychometric properties of two commonly used health status questionnaires in Parkinson's disease (PD): the generic Nottingham Health Profile (NHP) and the disease-specific 39-item Parkinson's disease Questionnaire (PDQ-39), from a cross-sectional postal survey of PD patients (N = 81), using traditional and Rasch measurement methodologies. Overall response rate was 88%. Both questionnaires were found feasible, although the NHP performed less well. The PDQ-39 had fewer floor effects and was better able to separate respondents into distinct groups than the NHP, whereas the latter exhibited less ambiguous dimensionality and better targeting of respondents with non-extreme scores. Reliability and validity indices were similar, and potential differential item functioning by age and gender groups was found for both questionnaires. PDQ-39 response alternatives indicated ambiguity. With few exceptions, questionnaire scales were unable to meet recommended standards fully. While preliminary, this study illustrates the need for thorough evaluation of outcome measures and has implications beyond the questionnaires used here. Although promising, both questionnaires warrant further developmental work and stronger support of measurement validity before they could be considered fully suitable for valid use in PD, in particular in earlier stages of the disease.     

Melatonin response to bright light in recovered, drug-free, bipolar patients.

Melatonin suppression by bright light was investigated in 15 drug-free euthymic bipolar patients and control subjects matched for age and sex with the patients. There were no differences between groups on the extent of melatonin suppression by 500 lux bright light administered between 0200h and 0400h. These results do not support the hypothesis that melatonin suppression by bright light is a reliable trait marker in recovered bipolar patients.     

Use of a synthetic peptide-based elisa for the diagnosis of infectious mononucleosis and other diseases

A simple enzyme immunoassay has been developed based on measuring antibodies to synthetic peptides corresponding to sequences in the Epstein-Barr nuclear antigen (EBNA). This assay, which is reproducible, quantitative, and simple to perform and interpret, can be an effective tool to aid in the diagnosis of infectious mononucleosis and nasopharyngeal carcinoma.     

Synthetic peptides from a conserved region of gp120 induce broadly reactive anti-HIV responses.

In our efforts to identify products that might be used for active immunotherapy in human immunodeficiency virus (HIV) infection, we have studied synthetic peptides derived from the CD4 attachment site of gp120. Two peptides have emerged with particularly interesting properties. The first (B138) is linear and spans the envelope residues 421-438; the second (1005/45) encompasses amino acids 418-445 and is cyclized by way of a disulphide bond joining its terminal cysteines. Both species have been shown to inhibit syncytial formation in a conventional bioassay, B138 being the most efficient. Both peptides elicit high titres of anti-peptide antibodies in immunized mice, rabbits and goats, with titres exceeding 1:10(5) in many cases. A substantial portion of this response is directed against gp120 as determined by enzyme-linked immunosorbent assay (ELISA). Analysis by flow cytometry has demonstrated that the antisera are broadly reactive with multiple diverse strains of HIV. The anti-gp120 activity of the anti-peptide antiserum was further confirmed by radioimmuno-precipitation (RIP) assays. Furthermore, RIP analysis and inhibition experiments in a GD4-gp120 binding assay have revealed that anti-peptide sera contain antibodies directed against the CD4 attachment site on gp120 and interfere with this receptor-ligand interaction.     

Initial evaluation of a continuous speech recognition program for radiology

The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers, and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging examinations performed with 6 different modalities. The dictated and original report texts were compared, and error rates for overall, significant, and subtle significant errors were computed. Error rate dependence on modality, native English speaker status, and gender were evaluated by performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in accuracy between men and women was found; however, significant differences were seen for overall and significant errors when comparing native and nonnative English speakers (P = .009 and P = .008, respectively). The speech recognition software is approximately 90% accurate, and while practical implementation issues (rather than accuracy) currently limit routine use of this product throughout a radiology practice, application in niche areas such as the emergency room currently is being pursued. This methodology provides a convenient way to compare the initial accuracy of different speech recognition products, and changes in accuracy over time, in a detailed and sensitive manner.     

Effect of heated humidified gases on temperature drop after cardiopulmonary bypass

In an attempt to prevent the decrease in nasopharyngeal temperature (NPT) ("afterdrop") after cardiac surgery, 30 patients undergoing hypothermic cardiopulmonary bypass (CPB) were randomly assigned to receive humidified heated inspired gases at 45 degrees C at the proximal end of the endotracheal tube (group I) or dry gases at room temperature (group II), from the time of termination of CPB. All patients received high flow rates on CPB during the rewarming period with the use of vasodilator drugs when necessary. Both groups were comparable with respect to total bypass time, rewarming time, and temperature at termination of CPB. In addition, the NPT was compared with the tympanic membrane temperature (TMT) in group I to assess the validity of the NPT under these conditions. The results indicate that heating and humidifying inspired gases do not prevent afterdrop and do not falsely increase the nasopharyngeal temperature. The reasons for the ineffectiveness of heated humidified gases may include a large heat deficit at termination of CPB despite a normal NPT, and the very small heat content of heated gases. Monitoring the temperature of a site that reflects the heat deficit, and a more complete rewarming during CPB are suggested as a better approach to the prevention of afterdrop.     

Objective Pulse-Synchronous "Essential" Tinnitus due to Narrowing of the Transverse Dural Venous Sinus

Subjective tinnitus is a common problem with many etiologies. Objective tinnitus, in which the sound is perceived by both the patient and the examiner, is less common. Objective tinnitus of the vascular type, in which a pulse synchronous bruit is heard by an independent observer, is frequently related to an underlying arterial or arteriovenous malformation, most commonly a dural arteriovenous fistula (DAVF) involving the transverse and sigmoid sinuses. The remaining cases are usually termed "essential" vascular tinnitus, and are presumed to have a venous etiology. In these cases, the audible noise is generally assumed to be produced within the sino-jugular connection, or within an enlarged jugular bulb. We present four documented cases of objective pulse synchronous tinnitus due to focal narrowing (acquired and developmental) of the mid-portion of the transverse dural sinus. In all cases, a bruit was audible directly over a focal constriction in the sinus, demonstrated by cerebral angiography or direct catheter venography. In one case, selective venography revealed a distensible sinus narrowing, associated with a jet of contrast marking fast flow within a developmental sinus segmentation. In another case, a loud pulse synchronous bruit was heard directly over a focal transverse sinus stenosis, which was detected by angiography at the site of a vascular surgical clip. In this case, magnetic resonance (MR) falsely predicted sinus occlusion. In two other cases, an audible bruit was also heard directly overlying a narrowed transverse sinus, seen in the venous phase of angiography. Transverse sinus stenosis is an unappreciated cause of objective pulsatile tinnitus, and we believe that this mechanism may underlie many cases of "essential" or venous etiology tinnitus not otherwise anatomically explained. Non-invasive testing, computed tomography (CT) and MR and non-directed angiography may overlook it. Conventional catheter arteriography or venography should be performed in such cases, with attention to the dural sinuses, if other tests fail to define the anatomic basis of the audible bruit.