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Biomedical subjects

B Gordon

Publications and source records attributed to B Gordon.

At least 37 records · Page 2Linked to original sources

Delineation of single-word semantic comprehension deficits in aphasia, with anatomical correlation.

In 3 of 18 aphasic patients pure deficits in semantic comprehension at the single-word level were defined through a series of tasks that excluded possible confounding deficits in auditory perception, visual perception, or speech production. In these pure cases, deficits were found at the superordinate, equivalence, and subordinate levels of single-word semantic processing. Pure semantic deficits were found to be correlated with damage to the left posterior temporal and inferior parietal region; patients whose damage spared this area did not evince such deficits, and the converse was also true. This study confirms the existence of separable deficits in semantic comprehension and points conclusively to the left posterior temporal and inferior parietal region as being critical for semantic processing. This anatomical localization is in keeping with anatomical studies from nonhuman primates, suggesting that these regions may be concerned with multimodal processing and integration of language.

Aphasia

Parameters for direct cortical electrical stimulation in the human: histopathologic confirmation.

Safe parameters for electrical cortical stimulation in humans are difficult to estimate from the animal experimental literature. We therefore examined the light microscopic histology at a total of 11 sites of direct subdural electrical stimulation, taken as part of anterior temporal lobectomies in 3 patients. Stimulations had been done through 3.175 mm diameter electrodes, with 0.3 msec square wave pulses of alternating polarity at 50 pulses/sec. In 2 patients, one site each had been used as a common reference for stimulation, receiving over 251 stimulation trials, most of 2-5 sec duration, at currents of 12.5-15.0 mA, 1 day prior to resection. The maximum charge per phase was 4.0-4.4 microC; the maximum charge density was 52-57 microC per geometric cm2 per pulse at the electrode surfaces. Comparison of hematoxylin and eosin, periodic acid-Schiff, and cresyl violet-stained material from the electrode sites with that from other regions did not show any histologic abnormalities attributable to the electrical stimulation. The relatively brief and intermittent periods utilized for human stimulation testing do not appear to cause structural damage at the light microscopic level at charge densities that exceed the threshold for damage established in animal studies with more continuous, chronic stimulation schedules.

Electric Stimulation

The basis for choice reaction time slowing in Alzheimer's disease.

Slowed reaction time has been suggested as an early feature of Alzheimer's disease (AD), but the basis for this slowing has not been established. Patients with mild AD were compared with controls on a choice reaction time task, both cued (CCRT) and uncued (CRT). Initial and 1-year followup data were analyzed both as mean reaction times and as parameters of a fitted two-component quantitative model (the ex-Gaussian model). Slowing of CRT proved to be a sensitive test for AD. Slowing was due to changes in both the sensory/motor and the decisional components of the CRT model. However, these changes were found in both AD and slower, older controls. The modeling of CRT in AD is discussed.

Aged

Evaluation of high performance liquid chromatography (HPLC), enzyme linked immunosorbent assay (ELISA) and particle concentration fluorescence immunoassay (PCFIA) methods for the screening, quantitation and pharmacokinetic study of furosemide in horses.

Equine plasma and urine samples were analyzed by using a high-performance liquid chromatography (HPLC), enzyme-linked immunosorbent assay (ELISA) and particle concentration fluorescence assay (PCFIA). Although ELISA and PCFIA were rapid, simple and sensitive for the screening of furosemide, they did not give reproducible quantitative results. The HPLC method, which required relatively longer analysis time, provided simple and reproducible quantitative analysis of furosemide in plasma and urine. The performance of the three methods was compared for the quantitation of furosemide in plasma obtained from thoroughbred mares dosed intravenously with furosemide (500 micrograms/kg (n = 7) and 1.0 mg/kg (n = 5)). Although the plasma furosemide profiles determined by ELISA, PCFIA and HPLC were similar, ELISA and PCFIA methods exhibited considerable variation in values. At high furosemide concentrations, the PCFIA method gave better quantitative values than ELISA. However, at trace furosemide concentrations the PCFIA method gave false positive values which were not confirmed by HPLC or ELISA. The pharmacokinetic values obtained from the HPLC data and the pharmacokinetic values obtained previously from the gas chromatographic data were comparable. The data obtained by ELISA and PCFIA were not suitable for the pharmacokinetic calculations.

Animals

Early-onset dementia and extrapyramidal disease: clinicopathological variant of Gerstmann-Straussler-Scheinker or Alzheimer's disease?

A case of progressive dementia and extrapyramidal signs beginning at age 29, with a ten year course until death, is presented. Necropsy examination showed an assortment of plaque types (including striatal plaques), neurofibrillary tangles, granulovacuolar degeneration, and depigmentation of the substantia nigra and locus ceruleus. This case had pathological features found in both Gerstmann-Straussler-Scheinker disease and in Alzheimer's disease. While somewhat similar to several other cases with features of both diseases, it differs in the presence of dystonia and striatal plaques. Although such cases may be difficult to categorize at present, they must be considered in the differential diagnosis of early onset dementia.

Adult

Lesions of nonvisual inputs affect plasticity, norepinephrine content, and acetylcholine content of visual cortex.

1. The depletion of both norepinephrine (NE) and acetylcholine (ACh) in the visual cortex can decrease plasticity. This decrease in plasticity, although dramatic under some circumstances, fails to occur under others. 2. We depleted cortical NE and ACh in 35- to 42-day-old kittens by making a lesion of the white matter behind the cingulate gyrus. One eye was sutured on the day of the lesion. We recorded from the visual cortex 7 days or 2-3 mo later and used the influence of the deprived eye on the cortical cells as a measure of plasticity. 3. We measured NE content by high-pressure liquid chromatography (HPLC) and inferred ACh depletion from depletion of choline acetyltransferase (ChAT) activity. NE depletion averaged 60% in the successfully depleted animals. Depletion of ChAT activity was consistent with NE depletion. 4. When recording occurred 7 days after the lesion and the sutured eye was contralateral to the lesion, plasticity was decreased on the side with the lesion; 70% of the cells were driven by the deprived eye. On the control, uninjured side only 15% of the cells were driven by the deprived eye. 5. In two circumstances the lesion did not cause a decrease in plasticity. In animals with suture ipsilateral to the lesion, the cortex remained plastic. In these animals only 26% of the cells in the hemisphere with the lesion were driven by the deprived eye. The cortex also retained its plasticity if the contralateral eye remained sutured for several months after the lesion, even though there was no recovery from NE and ACh depletion. 6. We conclude that depletion of NE and ACh does decrease plasticity; that is, it protects the deprived eye from losing its ability to drive cortical cells, at least for a short period of time. Depletion protects only the normally dominant contralateral pathway; the ipsilateral visual pathway remains plastic. 7. Perhaps the importance of the side of the deprived eye can be explained by assuming that depletion of NE and ACh removes facilitatory input. This would decrease the ability of cortical cells on the side with lesion to potentiate the input from the nondeprived eye relative to the deprived eye; that is, it would decrease the molecular deprivation (MD) effect. A removal of facilitation would also increase the visual input required to drive cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine

Resection of the epileptogenic area in critical cortex with the aid of a subdural electrode grid.

Electrode grids were implanted subdurally in 28 patients with epilepsy. In 16 of the 28 patients, an epileptogenic area was located in the speech-dominant left temporal lobe. Recordings made with the grid revealed that the epileptogenic areas in the patients varied widely in extent: the area was confined within the first 10 mm of the temporal lobe in some patients or it was scattered throughout the entire anterior to posterior 80-mm extend in others. Resection of the epileptogenic area was adjusted accordingly in each case. In 6 of 16 patients who were left-hemisphere-dominant for language, up to 55-80 mm from the tip of the temporal lobe was removed, a measure that exceeds the conventional limit of 50 mm from the tip of the dominant hemisphere. In the remaining 12 of the 28 patients, epileptogenic areas were located in a combination of several lobes. In 7 of these 12 patients, the epileptogenic area encompassed the rolandic area; it was removed without deficit in 4 patients and with expected deficit in 3. Of the latter 3 patients, 1 patient underwent hemispherectomy, and a large portion of the epileptogenic rolandic cortex in the frontal and parietal lobes was removed from the other 2. There were 2 cases of grid-related infection, which cleared with antibiotic treatment; there were no lasting complications of grid implantation in any patient. There was no mortality. Electroencephalographic recording and functional mapping using subdural electrode grids allow a tailored, maximal resection of epileptogenic tissue with minimal injury to critical cortex.

Brain Diseases

HIV-1 infection: no evidence of cognitive decline during the asymptomatic stages. The Multicenter AIDS Cohort Study.

Cross-sectional studies have not adequately resolved the question of whether subjects infected with HIV-1 may suffer cognitive decline during the early, asymptomatic stages of the infection. We studied longitudinally 238 asymptomatic healthy HIV-1-infected homosexual/bisexual men (CDC groups 2 and 3) and 170 uninfected controls in the Multicenter AIDS Cohort Study with neuropsychological testing at semiannual intervals. A comparison of change in scores between visits 1 and 4 as well as a multivariate autoregressive analysis revealed no evidence of decline in test performance over time in the HIV-1-infected group compared with the seronegative controls. These findings suggest that a gradual cognitive decline does not occur during the early, asymptomatic stages of HIV infection.

Adult

Dextromethorphan for treatment of complex partial seizures.

We performed a double-blind, crossover, add-on study of the antitussive agent dextromethorphan (DM 120 mg/d) as therapy for seizures on 9 patients suffering from severe complex partial seizures. DM had no significant influence on key laboratory values, nor on anticonvulsant drug levels. Side effects were negligible. Complex partial seizure frequency increased 25% during the DM arm of the study, although this increase was not clinically significant.

Adult

Characterization of the basal temporal language area in patients with left temporal lobe epilepsy.

We evaluated 5 consecutive patients with subdural grid electrodes (including placement over the left basal temporal region) for focal resections for control of intractable epilepsy. All 5 had language dysfunction when we performed cortical stimulation over the basal temporal region (the inferior temporal gyrus, the parahippocampal gyrus) using a systematic battery of language tests. The area in which language interference could be produced began from at least 11 to 35 mm posterior to the temporal tip and ended at least 39 to 74 mm posterior to the temporal tip. The most consistently impaired language tasks were spontaneous speech and passage reading, but there was impairment of all language functions tested in some patients. Language deficits after dominant temporal lobectomy may result from resection of this area.

Adult

Persistence of high leucocyte sodium and blood pressure after pre-eclampsia.

Blood pressure and leucocyte sodium content were measured in black Jamaican patients with pre-eclampsia and pregnant controls. Similar measurements were made in a group of mothers who had pre-eclampsia 36-38 weeks previously and their controls. An increase in cell sodium accompanied the high blood pressure in patients with pre-eclampsia. There was also some elevation of both blood pressure and cell sodium in patients who had had pre-eclampsia 36-38 weeks previously. These findings suggest that disturbances of cellular electrolytes continue into the post-partum period. Changes in intracellular sodium may be important in the pathogenesis of pre-eclampsia as they parallel the increase in blood pressure levels.

Adolescent

Screening of steroids in horse urine and plasma by using electron impact and chemical ionization gas chromatography-mass spectrometry.

Gas chromatography with chemical ionization mass spectrometry and selected-ion monitoring provided a sensitive method for the screening and confirmation of steroids in horse urine and plasma. Chemical ionization mass spectrometry was more sensitive than the electron impact ionization mass spectrometry for most of the steroids except for testosterone, prednisone-metabolite-2 and prednisolone-metabolite-2. The chromatographic conditions used in this study provided clean separation of different natural and synthetic steroids. Approximately 75-85% of the steroids added to plasma and approximately 65-70% of the steroids added to urine were recovered by the extraction procedure used in this study.

Animals

Screening and confirmation of drugs in horse urine by using a simple column extraction procedure.

A simple and reproducible column (Clean Screen-DAU, copolymeric bonded-phase silica column) extraction procedure has been described for the screening and confirmation of drugs in horse urine. The recovery of drugs by the column extraction was better than or comparable to the recovery by the liquid-liquid extraction, which is commonly used in the equine analytical laboratories. The column extraction provided broad coverage of drugs, separated extracts into three fractions (acidic/neutral, steroids, basic), produced a cleaner extract, and eliminated the need for special liquid-liquid extraction procedures for different drugs. The column extract was cleaner and did not contain impurities, whereas, the liquid-liquid extract was relatively impure and the extract required further thin-layer chromatographic cleanup. The column extraction procedure was used to confirm the presence of several potent drugs, such as fentanyl, etorphine, and mazindol.

Animals

Release of exogenously-supplied and endogenous serotonin from tissue slices of Hymenolepis diminuta.

The release of exogenously-supplied [3H]serotonin and of endogenous serotonin from H. diminuta tissue slices was studied using high [K+] depolarization. The release of [3H]serotonin was not calcium-dependent or magnesium-antagonized. While high-magnesium antagonism of endogenous serotonin release was inconclusive, this release was calcium-dependent. These findings suggest that, while exogenous serotonin is not taken into and released from nervous tissue, endogenous serotonin appears to be released from nervous tissue in a neurotransmitter-like manner.

Animals

Simultaneous analysis of furosemide and bumetanide in horse plasma using high performance liquid chromatography.

A high performance liquid chromatographic method is described for the simultaneous determination of furosemide and bumetanide in horse plasma. The C8 (3 microns) reversed phase column (4.8 x 150 mm) provided clear separation of furosemide and bumetanide with other components present in the horse plasma. The detection limit for both the drugs was 10 ng/mL. Both drugs were stable in plasma (at natural or acidic pH) for up to 24 h. The method is sufficiently sensitive to detect furosemide levels in plasma obtained from horses receiving a therapeutic dose of furosemide.

Animals

Local cerebral glucose abnormalities in mild closed head injured patients with cognitive impairments.

Mild-moderate closed head injury (CHI) can be followed by neuropsychological impairments in recent memory and attention, despite the absence of discernible structural abnormalities in a significant number of patients. To determine whether CHI may result in cerebral glucose metabolic abnormalities, we used fluorodeoxyglucose (FDG) technique with PET imaging to measure local cerebral metabolic rates for glucose (LCMRGlu) in three CHI patients and three matched normal controls. The CHI patients were between 3-12 months post-injury. All had deficits in attention and recent memory shown by neuropsychological testing. CT, MRI, EEG and drug screens were negative at the time of PET scanning. Subjects were engaged in a vigilance task throughout the initial 30 min following FDG administration. Group comparisons were made using t tests. There were no significant group differences found in global glucose metabolic rate. Nevertheless, the CHI group exhibited significantly decreased LCMRGLu in medial temporal, posterior temporal, and posterior frontal cortices, as well as in the left caudate nucleus. LCMRGlu was significantly increased, relative to controls, in anterior temporal and anterior frontal cortices. These results suggest that CHI patients can have regional glucose metabolic abnormalities, indicative of altered neuronal function, despite the absence of discernible anatomic abnormalities.

Brain

6-Hydroxydopamine treatment and beta adrenergic receptor binding in kittens. Relation to visual cortical plasticity.

Under some circumstances intraventricular administration of 6-OHDA decreases visual cortical plasticity of kittens; the mechanism for this change is not known, but depletion of norepinephrine (NE) is not the entire explanation. We have examined the effects of 6-OHDA treatment on beta adrenergic receptor binding in kitten visual cortex. Subjects were given vehicle solution alone, a low dose of 6-OHDA which depleted cortical NE without affecting visuocortical plasticity, or a higher dose of 6-OHDA which depleted cortical NE and decreased visuocortical plasticity. Drugs were administered in single daily injections via intraventricular cannulas. Saturation assays were performed on homogenates of visual cortical tissue using 125I-pindolol (30-400 pM) along w/ isoproterenol (237 microM) as a cold competitor. We measured radioactivity bound to tissue and retained on filters and analyzed the data using the EBDA computer program (McPherson 1983, 1985); we determined the affinity constant (Kd) and receptor density (Bmax) in multiple assays for each animal. Despite 75-90% NE depletion in both experimental groups, only the group receiving the lower dose of 6-OHDA showed any evidence of supersensitivity. The Kds did not differ among the groups. The data suggest that the effects of 6-OHDA on visuocortical plasticity are not secondary to beta adrenergic supersensitivity.

Animals

Family members' perspectives on psychiatric hospitalization and discharge.

Families of currently hospitalized patients in an extended-care psychiatric facility were interviewed concerning their views of hospitalization and discharge. Although most were sad that their relative was hospitalized, only a third felt that they would rather be caring for their relative at home. Families felt communication with hospital staff was poor and many of their needs were unmet. Families indicated a number of concerns around discharge. If clients were to be discharged soon, most families felt the clients needed a highly structured supervised living arrangement.

Adult