Biomedical subjects

B L Miller

Publications and source records attributed to B L Miller.

At least 109 records · Page 6Linked to original sources

PubMed1997

A study of the Lund-Manchester research criteria for frontotemporal dementia: clinical and single-photon emission CT correlations.

We evaluated the Lund-Manchester research criteria (LMRC) for frontotemporal dementia (FTD). With single-photon emission CT, we diagnosed 30 patients with FTD. These patients were compared with 30 with a research diagnosis of Alzheimer's disease (AD). We scored every patient on each LMRC item and compared the two groups. A discriminant function showed that loss of personal awareness, hyperorality, stereotyped and perseverative behavior, progressive reduction of speech, and preserved spatial orientation differentiated 100% of FTD and AD subjects. Items relating to affect and physical findings were not different in FTD versus AD. Loss of personal awareness, eating, perseverative behavior, and reduction of speech are the LMRC items that most clearly differentiate FTD from AD.

Alzheimer Disease↗

PubMed1997

Midline cerebral morphometry distinguishes frontotemporal dementia and Alzheimer's disease.

We investigated and contrasted midline cerebral structures in frontotemporal dementia (FTD) and Alzheimer's disease (AD). FTD and AD may be difficult to distinguish clinically. FTD typically affects frontal and anterior temporal regions, whereas AD tends to involve more posterior temporal and parietal areas. We hypothesized that disease-specific cerebral alterations would be differentially reflected in corresponding regions of the corpus callosum (CC), pericallosal CSF space (PCS), or their ratio (CC:PCS). Regions-of-interest (ROIs) from midsagittal MRIs in 17 AD, 16 FTD, and 12 elderly control (EC) subjects were analyzed. ROIs were divided into four regions using an anatomic landmark-based computer algorithm and were adjusted for head size variation. FTD subjects had a much smaller anterior CC region and significantly larger PCS area, particularly in anterior regions. AD and EC subjects did not differ significantly in any total or regional ROI measure. Total and anterior CC:PCS ratios were markedly lower in FTD patients. Across groups, total CC:PCS correlated significantly with midsagittal cerebral area and was similarly associated with Mini-Mental State Examination score. Anterior CC (AD) and PCS (FTD) regions exhibited disease-specific relationships to these variables. A discriminant model using two ROI variables correctly classified 91% of AD and FTD patients, comparing favorably with blind clinical MRI diagnostic ratings. Midline cerebral structural alterations reflect differential patterns of cerebral degeneration in AD and FTD, yielding morphometric indices that may facilitate the study of brain-behavior relationships and differential diagnosis of dementia.

Aged↗

PubMed1997

Influence of timing of gain on growth and reproductive performance of beef replacement heifers.

Our objective was to determine whether beef heifers could be developed by delaying the majority of weight gain until the last third of the developmental period before the onset of the breeding season. Spring-born Angus x Hereford heifers were used in each of two consecutive years and were allotted at weaning to gain either .45 kg/d for the entire developmental period (yr 1 = 159 d, n = 40; yr 2 = 168 d, n = 40; EVENGAIN) or to gain .11 kg/d from d 0 to 112, followed by .91 kg/d from d 112 to 159 (yr 1, n = 40) or d 168 (yr 2, n = 40; LATEGAIN). Body weights and condition scores were determined at d 0, 112, and 159 (yr 1) or d 0, 112, and 168 (yr 2). Heifers were subjected to a 60-d breeding season. Frame scores and pelvic areas were determined at the conclusion of the breeding season. Actual daily gains for EVENGAIN heifers for yr 1 and yr 2 were .60 and .51 kg/d, respectively. LATEGAIN heifers gained .25 and .05 kg/d during the restricted phases from d 0 to 112, followed by 1.14 and 1.32 kg/d during the accelerated growth phases for yr 1 and 2, respectively. Body weight at the onset of the breeding season and weight at puberty were not different between treatments in either year. Age at puberty did not differ in yr 1, but, age at puberty in yr 2 was delayed (P < .01) in LATEGAIN (406.9 d) compared to EVENGAIN (386.3 d) heifers. The LATEGAIN and EVENGAIN heifers had similar pelvic areas, frame scores, and body condition scores in each year. First-service conception rates of both groups were similar in yr 1 (55.5 vs 55.3%). In yr 2, LATEGAIN heifers tended (P = .18) to have an increase in first-service conception rate compared to EVENGAIN heifers (71.1 vs 56.4%). No treatment differences occurred in either average age of conception or overall pregnancy rates at the conclusion of the breeding season for either year. The LATEGAIN heifers were developed to a similar BW on 12 (P < .01) and 2.5% (not statistically significant) less feed for yr 1 and 2, respectively, compared to EVENGAIN heifers. We interpret these data to indicate that delaying the majority of weight gain until late in heifer development may decrease costs without detrimental effects on reproductive performance.

Analysis of Variance↗

PubMed1997

Frontotemporal dementia: treatment response to serotonin selective reuptake inhibitors.

BACKGROUND: Patients with frontotemporal dementia (FTD) present initially with primarily behavioral rather than cognitive symptoms. Decreased serotonin receptor binding has been reported in the frontal lobes, temporal lobes, and hypothalamus in autopsy-proven FTD cases. This study tests the hypothesis that many of the behavioral symptoms of FTD (including disinhibition, depressive symptoms, carbohydrate craving, and compulsions) will respond to serotonin selective reuptake inhibitors (SSRIs). METHOD: Eleven subjects meeting the Lund-Manchester clinical, neuropsychological, and neuroimaging criteria for FTD were treated with SSRIs (fluoxetine, sertraline, or paroxetine). After 3 months, treatment responses for disinhibition, depressive symptoms, carbohydrate craving, and compulsions were evaluated prospectively without placebo control. RESULTS: After treatment, disinhibition, depressive symptoms, carbohydrate craving, and compulsions all showed improvement in at least half the subjects in which they had been present. One subject stopped sertraline treatment because of diarrhea, while another stopped paroxetine treatment due to increased anxiety. The presence of individual behavioral symptoms and also the response of each symptom to SSRIs were unrelated to cognitive impairment as measured by baseline Mini-Mental Status Examination (.07 < or = p < or = 1.00) [corrected]. CONCLUSION: The behavioral symptoms of FTD may improve after treatment with SSRIs. Future neurochemical studies and controlled pharmacologic trials may improve available treatments.

1-Naphthylamine↗

PubMed1996

Neuropsychological deficits among older depressed patients with predominantly psychological or vegetative symptoms.

Depressed outpatients having primarily psychological or vegetative symptoms, as defined by the factor analytically developed Hamilton Depression Scale superfactors described by Rhoades and Overall (1983), were compared with similarly aged normal controls on a comprehensive neuropsychological battery. The vegetative group evidenced poorer performance than controls on several measures associated with right hemisphere functioning and on a task associated with executive functioning. In contrast, the psychological group did not significantly differ from controls on any measure, and had significantly better performance than the vegetative group on several tasks. These findings suggest that neuropsychological deficits associated with depression may be limited to those patients with primarily vegetative symptoms.

Aged↗

PubMed1996

Alzheimer disease and frontotemporal dementias. Behavioral distinctions.

BACKGROUND: Frontotemporal dementia (FTD) is a syndrome produced by lobar degeneration of the temporal and/or frontal lobes. OBJECTIVES: To quantify the behavioral disturbances of FTD and compare them with behavioral changes observed in Alzheimer disease (AD). DESIGN: Cross-sectional comparison of 2 groups defined by research diagnostic criteria and single photon emission computed tomography. Behaviors were assessed using a standardized rating scale-Neuropsychiatric Inventory. Groups were matched for dementia severity. SETTING: Patients were seen at 2 university-based outpatient dementia clinics and a Veterans Affairs medical center. PARTICIPANTS: Twenty-two patients with FTD and 30 patients with AD. RESULTS: Patients with FTD had significantly greater total Neuropsychiatric Inventory scores than patients with AD and exhibited more apathy, disinhibition, euphoria, and aberrant motor behavior. The Neuropsychiatric Inventory accurately assigned 77% of patients with FTD and 77% of patients with AD to the correct diagnostic group using disinhibition, apathy, and depression. Patients with FTD had higher levels of disinhibition and apathy with relatively lower levels of depression compared with patients with AD. CONCLUSIONS: The Neuropsychiatric Inventory provides a behavioral profile that differentiates patients with FTD from patients with AD. Patients with FTD are more behaviorally disturbed but are often less depressed than patients with AD relative to their level of apathy.

Aged↗

PubMed1996

Cerebral blood flow correlates of apathy in Alzheimer disease.

BACKGROUND: Apathy is a pervasive noncognitive neuropsychiatric disturbance in Alzheimer disease, which causes significant caregiver distress. The neuroanatomical substrate of apathy is not well understood. OBJECTIVE: To study the relationship between regional cerebral blood flow and the presence and severity of the personality disturbance, apathy, in individuals with Alzheimer disease. DESIGN: Analysis of the relationship between regional cerebral blood flow as measured by single photon emission computed tomography and severity of apathy as measured by the Neuropsychiatric Inventory using an analysis of variance design. We examined regional cerebral perfusion alterations as measured by xenon 133Xecalibrated technetium Tc 99m hexamethyl-propyleneamine-oxime single photon emission computed tomography in relation to the presence and severity of apathy. SETTING: The neurology clinics of the University of California, Los Angeles, UCLA School of Medicine, and Harbor-UCLA Medical Center. PARTICIPANTS: Thirty-one community-dwelling patients fulfilling National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association diagnostic criteria for probable Alzheimer disease who had a single photon computed tomographic scan performed within 3 months of administration of the Neuropsychiatric Inventory. RESULTS: The presence of apathy was associated with more severe prefrontal and anterior temporal dysfunction. These regional cerebral perfusion relationships with apathy were independent of cognitive decline except in the dorsolateral prefrontal cortex. CONCLUSIONS: These results demonstrate the association of apathetic syndromes with prefrontal and anterior temporal regional brain dysfunction and are consistent with similar findings previously reported in other disorders.

Aged↗

PubMed1996

In vivo 1H MRS choline: correlation with in vitro chemistry/histology.

We correlated the in vivo 1H Magnetic Resonance Spectroscopy (MRS) concentration of the choline peak (CHO) with in vitro chemical measures of choline-containing compounds and a histological grade of cellularity in 18 patients with neoplastic and infectious brain lesions. Gas-chromatography-mass-spectrometry (GCMS) was used to measure the concentrations of free choline (Cho), glycerophosphocholine (GPCho), phosphocholine (PCho) and phosphatidylcholine (PtdCho) from biopsies in the same area where MRS was performed. Cellular density, free Cho, PCho and GPCho were the strongest determinants of 1H MRS CHO while PtdCho was not. Just as the 1H MRS 2.0 peak reflects both the concentration of n-acetyl-l-aspartate and neuronal density, the 1H MRS 3.2 peak reflects the concentration of water-soluble choline-containing compounds and cellular density.

Brain↗

PubMed1996

Comparison of neuropsychological functioning in Alzheimer's disease and frontotemporal dementia.

Neuropsychological changes distinguishing mild Alzheimer's disease (AD) from frontotemporal dementia (FTD) have been described, but empirical verification of differential cognitive characteristics is lacking. Archival neuropsychological data on 15 FTD patients, 16 AD patients, and 16 controls were compared. Controls outperformed both patient groups on measures of verbal and nonverbal memory, executive ability, and constructional skill, with AD patients showing more widespread memory decline. No differences were found between the 3 groups in confrontation naming, recognition memory, or basic attention. Patient groups differed only in nonverbal memory, with FTD patients performing significantly better than AD patients. However, patient groups also differed in pattern of performance across executive and memory domains. Specifically, AD patients exhibited significantly greater impairment on memory than executive tasks, whereas the opposite pattern characterized the FTD group. These findings suggest that examination of relative rankings of scores across cognitive domains, in addition to interpretation of individual neuropsychological scores, may be useful in differential diagnosis of FTD versus AD.

Aged↗

PubMed1996

Neuroimaging findings in patients with AIDS.

An increasing number of patients are presenting with central nervous system complications of human immunodeficiency virus infection. New imaging technologies such as magnetic resonance imaging, magnetic resonance proton spectroscopy, single-photon emission computed tomography, and positron emission tomography are playing an ever-increasing role in the diagnosis of these complications. As therapeutic modes improve, imaging may assume a growing role in monitoring the responses to therapy among these patients.

AIDS Dementia Complex↗

PubMed1996

Suppression and enhancement of the Aspergillus nidulans medusa mutation by altered dosage of the bristle and stunted genes.

Asexual reproduction in Aspergillus nidulans is characterized by the orderly differentiation of multicellular reproductive structures (conidiophores) and chains of uninucleate conidia (spores). Mutations in the developmental modifier medusa (medA) result in aberrant conidiophores with branching chains of reiterated reproductive cells (metulae), delayed conidial differentiation and frequent reinitiation of secondary conidiophores. We show that incorrect morphology is in part a consequence of modified bristle (brlA) and abacus (abaA) expression, key regulators of the core genetic pathway directing conidial differentiation. First, correct temporal expression of both brlA transcripts (brlA alpha and brlA beta) requires MedAp. Second, MedAp functions as a coactivator required for normal levels of abaA expression. Finally, we show that wild-type morphology results from a finely tuned balance in the expression of brlA, medA and the developmental modifier stunted (stuA). One extra copy of brlA suppresses medA mutations and restores normal abaA mRNA abundance. In contrast, an extra copy of stuA in a medA- strain results in an enhanced medusoid phenotype with extensive metulae proliferation and nearly complete absence of conidia. abaA and brlA alpha transcription are completely repressed in these strains. In general, low stuA:brlA ratios promoted conidiation while high ratios caused proliferation of unicellular sterigmata and inhibited conidiation.

Aspergillus nidulans↗

PubMed1996

Cognition and white matter hyperintensities in older depressed patients.

OBJECTIVE: The authors compared amounts of white matter hyperintensity in late- and early-onset depressed patients and never-depressed older subjects, compared neuropsychological function in these groups, and investigated the association between white matter hyperintensities and cognitive function in depression. METHOD: Sixty currently depressed patients whose first depression occurred after age 50 years, 35 depressed patients over age 50 whose first depression occurred before age 35, and 165 nonpsychiatrically ill subjects over age 50 underwent magnetic resonance imaging (MRI) and neuropsychological evaluation. Areas of white matter hyperintensity were measured from MRI images. RESULTS: The late-onset patients had more white matter hyperintensity than either of the other groups. Compared to the nondepressed subjects, the patients had significantly lower scores in the cognitive domains of nonverbal intelligence, nonverbal memory, constructional ability, executive ability, and information processing speed. The cognitive abnormalities were mostly confined to the late-onset patients, and the presence of a large amount of white matter hyperintensity was associated with significantly poorer executive skills. However, most of the scores were not in the significantly impaired range. CONCLUSIONS: Large amounts of white matter hyperintensity are more frequent in patients with late-onsetdepression than in elderly subjects with early-onset or no depression. Both late- and early-onset elderly depressed patients show mild decrements in some "right hemisphere" cognitive skills; the late-onset subjects also show deterioration in information processing speed and executive functions. Patients with large amounts of white matter hyperintensity have significantly poorer executive function.

Age Factors↗

PubMed1996

Quantitative EEG in frontotemporal dementia.

Accurate diagnosis of the major degenerative dementias continues to be problematic. Although diagnostic precision for Alzheimer's disease (AD) approaches 90%, for Frontotemporal dementias (FTD) it has been less than 20%. Previous work has shown that AD patients have both focal and generalized slowing, while in FTD the EEG is normal. We studied 26AD,13FTD and 27 health control subjects with Quantitative Electroencephalography (QEEG). Using only five QEEG measures with stepwise discriminant function analysis, we distinguished the AD from FTD groups each with 84.6% accuracy, and controls (100%) from FTD groups (84.6%) with high accuracy. The most informative QEEG variables for distinguishing FTD and AD were relative power from the temporal region in beta-2 band, and from the parietal region in the theta and alpha and beta-2 bands. These results suggest that QEEG may be helpful in distinguishing subjects with AD from subjects with FTD.

Alpha Rhythm↗

PubMed1996

Neural basis of confabulation.

We present a case of acute alcohol-induced Korsakoff amnesia. A severe amnestic-confabulatory syndrome characterized the early clinical status. The initial neuropsychological tests demonstrated severe learning deficits plus impaired performance on many, but not all, tests of frontal lobe function. Single-photon emission CT (SPECT) at this stage showed hypoperfusion in the orbital and medical frontal regions and the medial diencephalic area. Four months later, the patient's amnesia remained but there was no confabulation. Repeat neuropsychological tests confirmed an ongoing severe amnesia, but performance on the frontal lobe tests now was normal. Repeat SPECT showed a return to normal perfusion in the frontal brain areas but little improvement in the medial diencephalic region. These findings along with data from the clinical literature suggest that confabulation results from dysfunction of orbital and a medial frontal cortex.

Adult↗

PubMed1996

Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop.

Recent neuropathologic autopsy studies found that 15 to 25% of elderly demented patients have Lewy bodies (LB) in their brainstem and cortex, and in hospital series this may constitute the most common pathologic subgroup after pure Alzheimer's disease (AD). The Consortium on Dementia with Lewy bodies met to establish consensus guidelines for the clinical diagnosis of dementia with Lewy bodies (DLB) and to establish a common framework for the assessment and characterization of pathologic lesions at autopsy. The importance of accurate antemortem diagnosis of DLB includes a characteristic and often rapidly progressive clinical syndrome, a need for particular caution with neuroleptic medication, and the possibility that DLB patients may be particularly responsive to cholinesterase inhibitors. We identified progressive disabling mental impairment progressing to dementia as the central feature of DLB. Attentional impairments and disproportionate problem solving and visuospatial difficulties are often early and prominent. Fluctuation in cognitive function, persistent well-formed visual hallucinations, and spontaneous motor features of parkinsonism are core features with diagnostic significance in discriminating DLB from AD and other dementias. Appropriate clinical methods for eliciting these key symptoms are described. Brainstem or cortical LB are the only features considered essential for a pathologic diagnosis of DLB, although Lewy-related neurites, Alzheimer pathology, and spongiform change may also be seen. We identified optimal staining methods for each of these and devised a protocol for the evaluation of cortical LB frequency based on a brain sampling procedure consistent with CERAD. This allows cases to be classified into brainstem predominant, limbic (transitional), and neocortical subtypes, using a simple scoring system based on the relative distribution of semiquantitative LB counts. Alzheimer pathology is also frequently present in DLB, usually as diffuse or neuritic plaques, neocortical neurofibrillary tangles being much less common. The precise nosological relationship between DLB and AD remains uncertain, as does that between DLB and patients with Parkinson's disease who subsequently develop neuropsychiatric features. Finally, we recommend procedures for the selective sampling and storage of frozen tissue for a variety of neurochemical assays, which together with developments in molecular genetics, should assist future refinements of diagnosis and classification.

Dementia↗

PubMed1996

Frontotemporal dementia versus Alzheimer's disease: differential cognitive features.

Frontotemporal dementia (FTD) is a common neurodegenerative dementia that can be difficult to distinguish clinically from Alzheimer's disease (AD). The differential distribution of pathology in FTD and AD predicts the presence of differential cognitive features on mental status examination. We compared 39 FTD patients with 101 AD patients on the Consortium to Establish a Registry in AD examination supplemented by cognitive areas from the Neurobehavioral Cognitive Status Examination. The FTD patients were diagnosed using noncognitive clinical and neuroimaging criteria and were comparable to the AD patients in terms of gender, educational level, and dementia severity ratings. The FTD patients performed significantly better than the AD patients on constructions and calculations. These findings were at the lower limits of normal for older normal controls and persisted after covarying for younger age and higher Mini-Mental Status Examination scores in the FTD group. In addition to personality and neuroimaging features, relatively preserved performance of elementary drawings and calculations in FTD suggests additional features for distinguishing FTD patients from comparably demented AD patients.

Aged↗

PubMed1996

Fulminant cerebral lymphoma in AIDS.

Three cases of cerebral lymphoma in patients with acquired immunodeficiency syndrome is presented. They are remarkable for their extremely rapid progression, which simulated an infectious processes during trials of antitoxoplasma therapy. Fourteen days of therapy are generally required to assess a negative response. However, earlier biopsies and shorter therapeutic trials may be indicated in these patients.

AIDS-Related Opportunistic Infections↗

PubMed1995

Identification, activity, and structural studies of peptides incorporating the phorbol ester-binding domain of protein kinase C.

The family of homologous enzymes known as protein kinase C (PKC) has been the object of intense interest because of its crucial role in cellular signal transduction. Although considerable information about the activation of PKC has been gained through structure-activity, molecular modeling, and synthetic studies of both natural and designed activators, information about the structure of PKC itself has been limited by its large size and requirement for phospholipid cofactors. Additionally, difficulties in the purification of truncated mutants of PKC have thus far prevented their analysis by nuclear magnetic resonance (NMR) or x-ray crystallographic methods. We describe the identification, synthesis, ligand-binding analysis, cofactor requirements, and preliminary NMR evaluation of two subdomains (peptides B and C) of the regulatory domain of PKC-gamma. Peptides B and C bind [3H]phorbol 12,13-dibutyrate with good affinity (Kd = 6.4 microM and 414 nM, respectively) in the presence of phosphatidylserine. In comparison, the binding affinity of [3H]phorbol 12,13-dibutyrate for PKC was found to be 2.6 nM. Like PKC itself, these peptides also recognize other PKC activators, including dioctanoylglycerol and teleocidin B-4, and exhibit an ability to differentiate phorbol ester from its C-4 epimer. NMR studies of PKC subdomains are also described, indicating that both peptides B and C are well behaved in solution and do not exhibit any concentration-dependent changes. Finally, these studies reveal that peptide B becomes conformationally ordered only in the presence of phospholipid, suggesting that the regulatory domain of PKC itself might be organized for activation only when associated with the lipid bilayer, where its activator (diacylglycerol) is encountered.

Amino Acid Sequence↗