PubMed Health⌕ Search

Biomedical subjects

M E Nichols

Publications and source records attributed to M E Nichols.

At least 19 recordsLinked to original sources
PubMed2000

Anosognosia and asomatognosia during intracarotid amobarbital inactivation.

BACKGROUND: Anosognosia (i.e., denial of hemiparesis) and asomatognosia (i.e., inability to recognize the affected limb as one's own) occur more frequently with right cerebral lesions. However, the incidence, relative recovery, and underlying mechanisms remain unclear. METHODS: Anosognosia and asomatognosia were examined in 62 patients undergoing the intracarotid amobarbital procedure as part of their preoperative evaluation for epilepsy surgery. Additional questions were asked in the last 32 patients studied. RESULTS: During inactivation of the non-language-dominant cerebral hemisphere, 88% of the 62 patients were unaware of their paralysis, and 82% could not recognize their own hand at some point. Only 3% did not exhibit anosognosia or asomatognosia. In general, asomatognosia resolved earlier than anosognosia. When patients could not recognize their hand, they uniformly thought that it was someone else's hand. Dissociations in awareness were seen in the second series of 32 patients. Although 23 patients (72%) thought that both arms were in the air, 31% pointed to the correct position of the paralyzed arm on the table. Despite the inability of 24 of 32 patients (75%) to recognize their own hand, 21% of these patients were aware that their arm was weak, and 38% had correctly located their paralyzed arm on the angiography table. CONCLUSIONS: Anosognosia and asomatognosia are both common during acute dysfunction of the non-language-dominant cerebral hemisphere. Dissociations of perception of location, weakness, and ownership of the affected limb are frequent, as are misperceptions of location and body part identity. The dissociations suggest that multiple mechanisms are involved.

Adolescent↗
PubMed1999

Differential cognitive effects of carbamazepine and gabapentin.

PURPOSE: The cognitive effects of the newer antiepileptic drugs (AEDs) compared with the older standard AEDs are uncertain. METHODS: We directly compared the cognitive effects of carbamazepine (CBZ) and gabapentin (GBP) in 35 healthy subjects by using a double-blind, randomized crossover design with two 5-week treatment periods. During each treatment condition, subjects received either GBP, 2,400 mg/day, or CBZ (mean, 731 mg/day) adjusted to a dose to achieve midrange standard therapeutic blood levels (mean, 8.3 microg/ml). Subjects were tested at the end of each AED treatment period and in four drug-free conditions [two pretreatment baselines and two post-treatment washout periods (1 month after each AED)]. The neuropsychological test battery included 17 measures yielding 31 total variables. RESULTS: Direct comparison of the two AEDs revealed significantly better performance on eight variables for GBP, but none for CBZ. Comparison of CBZ and GBP to the nondrug average revealed significant statistical differences for 15 (48%) of 31 the variables. Pairwise follow-up analyses of the 15 variables revealed significantly better performance for nondrug average on 13 variables compared with CBZ, and on four compared with GBP. GBP was better than nondrug average on one variable. CONCLUSIONS: Although both CBZ and GBP produced some effects, GBP produced significantly fewer untoward cognitive effects compared with CBZ at the dosages used in this study.

Acetates↗
PubMed1997

Level of consciousness and memory during the intracarotid sodium amobarbital procedure.

Controversy exists regarding differential effects on consciousness of left/right cerebral inactivation via intracarotid amobarbital. Further, the effects of level of consciousness (LOC) on memory during the intracarotid sodium amobarbital procedure (IAP) are unclear. A modified version of the Glasgow Coma Scale altered to avoid the confounding effects of aphasia was employed to assess LOC in 97 patients during the IAP. A greater impairment in LOC occurred with left cerebral inactivation. Memory was more impaired following left hemisphere injections as well as from injections contralateral to seizure focus. Memory was correlated with LOC, and this effect was more prominent for right hemisphere injections and for injections ipsilateral to seizure focus. These findings support differential cerebral roles in consciousness and demonstrate that IAP memory performance may be affected by the patient's LOC.

Adolescent↗
PubMed1997

Wada memory and timing of stimulus presentation.

We compared Wada memory performance for stimuli presented at two timing intervals following amobarbital injection in 47 non-lesional patients with complex partial seizures (L = 26; R = 21). A significant interaction between seizure focus and timing of presentation was present (P < 0.03). Memory performance for objects whose presentation began approximately 50-55 s following amobarbital administration differed as a function of ipsilateral vs. contralateral injection at a very high level of statistical significance (P < 0.00001). Items presented approximately 4 min, 30 s post injection were also related to seizure onset literality, but at a lower statistical level (P < 0.01). Presentation of Wada memory stimuli earlier during hemispheric anaesthesia yields results that are more sensitive to lateralized temporal lobe seizure onset than does presentation of items later during the procedure.

Adult↗
PubMed1995

Synergistic anticholinergic and antiserotonergic effects in humans.

Animal research suggests an important interactive role for ascending cholinergic and serotonergic systems in modulation of cerebral function. Employing a randomized, double-blind, crossover design, 11 healthy young adults were tested in each of four conditions: (1) placebo, (2) fenfluramine (a serotonin depleting agent), (3) scopolamine (a muscarinic antagonist), and (4) fenfluramine and scopolamine. P3 latency was slowed by the dual drug treatment to an extent greater than the sum of individual drug effects. EEG mean frequency was decreased by behavioral activation, and this decrease was reversed by the combined drug treatment but not by single drugs. In contrast, verbal memory, EEG alpha power, and P3 amplitude were significantly affected only by scopolamine. No drug effects were found for the N1 and P2 potentials. The results provide the first demonstration of combined anticholinergic and antiserotonergic effects in humans, and offer partial support to the concept of an interactive role of cholinergic and serotonergic systems in cerebral mechanisms.

Adult↗
PubMed1995

Wada memory asymmetries predict verbal memory decline after anterior temporal lobectomy.

We examined Wada memory and neuropsychological memory function in 34 nonlesional patients who underwent anterior temporal lobectomy (ATL) and who were seizure free at 1-year follow-up. Patients who displayed a decline on verbal memory measures that exceeded 1 SD after left ATL had significantly smaller left/right Wada memory asymmetries than left ATL patients without a significant verbal memory decline. When Wada memory asymmetries were used to predict verbal memory decline after left ATL in individual patients, similar statistically significant effects were present. No significant relationship between Wada memory and postoperative memory was present in right ATL patients, and postoperative memory function was not related to Wada memory performance after either left hemisphere or right hemisphere injection alone. We conclude that Wada memory asymmetries provide one measure of the risk to material-specific decline in verbal memory after left ATL.

Analysis of Variance↗
PubMed1995

Comparative cognitive effects of phenobarbital, phenytoin, and valproate in healthy adults.

The relative effects of antiepileptic drugs (AEDs) on cognition are controversial. We compared the cognitive effects of phenobarbital, phenytoin, and valproate in 59 healthy adults using a randomized, double-blind, incomplete-block, crossover design. Cognitive assessments were conducted at baseline, after 1 month on each drug (two AEDs per subject), and at two repeat baselines 11 weeks after each AED treatment. The neuropsychological battery included 12 tests, yielding 22 variables: Choice Reaction Time, P3 Event-Related Potential, Finger Tapping, Lafayette Grooved Pegboard, Selective Reminding Test, Paragraph Memory, Complex Figures, Symbol Digit Modalities Test, Stroop Test, Visual Serial Addition Test, Hopkins Symptom Checklist, and Profile of Mood States. More than one-half of the variables exhibited AED effects when compared with nondrug baselines, and all three AEDs produced some untoward effects. Differential AED effects on cognition were present for approximately one-third of the variables. Phenobarbital produced the worst performance; there was no clinically significant difference between phenytoin and valproate.

Adult↗
PubMed1994

Wada memory performance predicts seizure outcome following anterior temporal lobectomy.

We examined the ability of Wada memory testing to predict seizure outcome 1 year following anterior temporal lobectomy. Asymmetry scores for Wada memory performance, using amobarbital doses of 125 mg or less, were calculated for 55 patients under the age of 45 years who had no radiologic evidence of structural lesions other than gliosis. Wada memory asymmetries were significantly greater (p < 0.02) in patients who were seizure free compared with those who continued to experience seizures. Furthermore, patients with Wada memory score asymmetries of at least three objects (maximum = 8) were more likely to be seizure free compared with patients with Wada memory asymmetries less than three (p < 0.01). Of the 36 patients who had Wada memory score asymmetries of at least three objects, 32 (89%) were seizure free. In contrast, of the 19 patients whose Wada memory score asymmetries were less than three, only 12 (63%) were seizure free. These data suggest that Wada memory performance is related to seizure outcome following anterior temporal lobectomy.

Adult↗
PubMed1994

Effects of a novel azaspirane (SK&F 105685) on arthritic lesions in the adjuvant Lewis rat: attenuation of the inflammatory process and preservation of skeletal integrity.

OBJECTIVE: To determine the effects of SK&F 105685 (N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5] decane-2-propanamine dihydrochloride) on the arthritic lesions in the tibiotarsal joint of adjuvant arthritic (AA) rats. METHODS: Inhibition of hindpaw inflammation was measured by water displacement. The protective effects on joint integrity were determined by measuring radiographic and histological changes and by scanning electron microscopy. RESULTS: Compared to AA control rats, SK&F 105685 suppressed hindpaw edema 64% or 41-54% in AA rats receiving 30 or 20 mg/kg/day, respectively. Radiographic evaluation showed marked decreases in soft tissue swelling and in the severity of skeletal tissue loss at the tibiotarsal joint in both dose groups. Histologically SK&F 105685 markedly attenuated the extent and severity of the inflammatory lesion and preserved the basic integrity of bone and cartilaginous tissues, including the content and distribution of proteoglycans of the articular cartilages. Cellular changes included decreases in the inflammatory infiltrate and in the number of osteoclasts and chondroclasts. Whereas AA control rats exhibited marked to severe loss (41-70%) of skeletal tissue mass, the loss in rats given 30 mg/kg SK&F 105685 was mild (< 20%). Scanning electron microscopy of the talus revealed only slight erosion of the articular cartilage and general preservation of the underlying bone. In contrast, in AA controls, there was marked erosion of the talar articular cartilage and severe loss of subchondral bone. Spleen cells from SK&F 105685 treated rats had a reduced capacity to respond to concanavalin A and contained suppressor cell activity as measured in a coculture assay. CONCLUSION: Our studies show that SK&F 105685 has remarkable protective effects on the joints of AA rats and suggests that it may attenuate the overall inflammatory process and retard the degenerative loss of skeletal tissue in rheumatoid arthritis in humans.

Administration, Oral↗
PubMed1993

Evidence for a central cholinergic effect of high-dose thiamine.

In vitro animal studies have suggested that thiamine is involved in the presynaptic release of acetylcholine. Total thiamine content in cholinergic nerve terminals is comparable with that of acetylcholine, and the phosphorylation state of thiamine changes with release of acetylcholine. Thiamine binds to nicotinic receptors and may exhibit anticholinesterase activity. Based on these observations, we investigated the effects of pharmacological doses of thiamine on the cognitive deficits induced by the anticholinergic scopolamine in healthy young adults using a randomized, double-blind, placebo-controlled, double-crossover design. Drug effects were assessed by P3 event-related potential, quantitated electroencephalography, and free recall memory. Conditions included (1) baseline, (2) thiamine 5 gm p.o. and scopolamine 0.007 mg/kg IM, and (3) lactose PO and scopolamine 0.007 mg/kg IM. Thiamine significantly reduced adverse effects of scopolamine on P3 latency, spectral components of electroencephalography, and memory recall. The results are consistent with a cholinomimetic effect of thiamine in the central nervous system. Additional studies are needed to delineate the basic mechanisms and possible therapeutic efficacy of thiamine at pharmacological dosages.

Adult↗
PubMed1993

The role of cholinergic systems in visuospatial processing and memory.

Few studies have specifically addressed the cholinergic role in visuospatial memory. In the present study, we employed a randomized double-blind repeated measures design to investigate the effects of scopolamine on Judgement of Line Orientation (JLO) and two distinct visuospatial memory tasks. Complex Figures (CF) is a test of drawn reproduction similar to the Rey complex figure. The Spatial Array Memory Test (SAMT) is a two-dimensional free-recall visuospatial test which minimizes constructive skills and allows sensitive measurement of placement errors. Scopolamine impaired performance on JLO and CF. However, no effects of scopolamine on SAMT were apparent even though the SAMT is sensitive to aging and right temporal-lobe lesions. Selective effects of scopolamine on focused versus distributed attention may account for these differential results.

Adult↗
PubMed1993

Wada memory testing and hippocampal volume measurements in the evaluation for temporal lobectomy.

We examined the relationship of Wada memory performance and MRI hippocampal volume measurements to laterality of ultimate seizure localization in 20 patients with complex partial seizures who later underwent temporal lobectomy. Discriminant function analysis employing both Wada memory test asymmetries and hippocampal volume asymmetries correctly classified 100% of the patients into left and right temporal lobe groups. Wada memory asymmetries alone correctly classified 90% of the sample (80% of the sample when the discriminant function included all patients except the one being classified), and hippocampal volume asymmetries alone correctly classified 90% of the patients. A significant correlation was present between Wada memory asymmetries and hippocampal volume asymmetries (r = 0.78), indicating that structural evidence of reduced hippocampal volume has a functional correlate reflected by Wada memory performance. These data suggest that the combination of functional and structural measures is of value in the preoperative evaluation for epilepsy surgery.

Adult↗
PubMed1993

Neuropsychological effects of antiepileptic drugs: a current perspective.

Epilepsy has widespread direct and indirect effects on the patient's quality of life. These patients generally have neuropsychological impairments that lower their educational and occupational levels of achievement, and many have additional emotional and/or behavioral disorders. Multiple factors underlie the cognitive changes associated with epilepsy, including the effect of antiepileptic drug (AED) therapy itself. Although it is recognized that the beneficial results of reduced seizure frequency may compensate at least in part for detrimental cognitive AED side effects, polypharmacy and higher AED blood levels can shift this balance. Further, there is much debate concerning the existence and clinical importance of differential AED cognitive side effects. While all the major AEDs can produce cognitive side effects, more recent research indicates that the magnitude of these effects may not be clinically significant with monotherapy within standard therapeutic range. The impact of AED differential cognitive side effects on the patient's quality of life is only beginning to be appreciated as research focuses on this important aspect of patient management. The information gained from such investigations will influence not only current therapeutic decisions, but also the development of future anticonvulsants.

Adult↗
PubMed1989

In vitro evaluation of the role of the Duffy blood group in erythrocyte invasion by Plasmodium vivax.

A short-term in vitro culture system that allows for significant re-invasion of target erythrocytes by Plasmodium vivax was used to study the role of the Duffy blood group antigen as a ligand for merozoite invasion by this human malaria species. Using human Duffy-positive and -negative erythrocytes, various primate erythrocytes, enzymatic modification of erythrocytes, and mAb that defines a new Duffy determinant (Fy6) we conclude that the erythrocyte glycoprotein carrying Duffy determinants is required as a ligand for the invasion of human erythrocytes by P. vivax merozoites. Blockade of invasion by Fab fragments of the anti-Fy6 mAb equal to that of the intact molecule and the correlation of P. vivax susceptibility with the presence of the Fy6 determinant suggests this epitope or a nearby domain may be an active site on the Duffy glycoprotein. However, as for P. knowlesi, there is evidence that an alternate pathway for P. vivax invasion of simian erythrocytes may exist.

Animals↗
PubMed1989

Erythrocyte invasion by two Plasmodium falciparum isolates differing in sialic acid dependency in the presence of glycophorin A antibodies.

Merozoites of Plasmodium falciparum depend on glycophorins for invasion into human erythrocytes, although this dependency varies between different geographic isolates of the species. The FCR-3 (Gambia) isolate appears to be fully dependent on the N-acetylneuraminic acid (NeuNAc) residues of the O-linked tetrasaccharide of glycophorin for invasion. Invasion of the CDC-1 (Honduras) isolate into neuraminidase treated erythrocytes is 50% of that into normal erythrocytes. This and additional results suggest that this isolate is not fully dependent on the O-linked saccharides of glycophorin. In the present study, invasion of CDC-1 and FCR-3 isolates into erythrocytes was examined in the presence of Fab fragments of monoclonal antibodies directed against different domains of glycophorin. Fab fragments directed against the carbohydrate domain inhibited invasion of both isolates but inhibited invasion by the FCR-3 isolate more than CDC-1 isolate. The reactivity of monoclonal antibodies (Mabs) directed against the carbohydrate domain was dependent on the NeuNAc residues as binding was abolished in neuraminidase treated erythrocytes. Mabs directed against the peptide domain of glycophorin A did not significantly inhibit invasion by either isolate. These results are consistent with other findings that the CDC-1 isolate is not fully dependent on the carbohydrate domain of glycophorin for invasion.

Animals↗
PubMed1987

A new human Duffy blood group specificity defined by a murine monoclonal antibody. Immunogenetics and association with susceptibility to Plasmodium vivax.

A new Duffy specificity, Fy6, defined by a murine monoclonal antibody of the IgG1 kappa class, is related to susceptibility to malarial invasion. In humans, Fy6 is present on the red cells of all persons except those of the Fy(a-b-) type, a distribution resembling that of Fy3. However proteolytic enzyme treatment of red cells enhances the reactivity of Fy3, whereas Fy6, like Fya and Fyb, is susceptible to degradation by this process. The number of Fy6 sites on human red cells was found to be 12,200 per cell, in close agreement with earlier estimates of the number of Fya sites. Anti-Fy6 reacted in western blots with a membrane glycoprotein of approximately 46,000 Mr, not significantly different from that of a molecule known to bear the Fya determinant. The Fy6 epitope is shown to be present on the red cells of some but not all nonhuman primate species, where it has a distribution not only distinctly different from Fya, Fyb, and Fy3, but in close accordance with susceptibility to penetration by Plasmodium vivax. Thus, the red cells of two species of macaques (Macaca mulatta and M. fascicularis), which are invaded by Plasmodium knowlesi but not by P. vivax are shown to have other Duffy antigens but to be devoid of Fy6. It appears, therefore, that the red cell epitopes used by these closely related species are distinct, and that susceptibility to P. vivax merozoite penetration is dependent on the presence of Fy6.

Animals↗