Discriminant analysis of Alzheimer's disease.
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Alzheimer Disease↗
Biomedical subjects
D G Murphy
Publications and source records attributed to D G Murphy.
The effects of sex steroids, and the X chromosome, on female brain function: a study of the neuropsychology of adult Turner syndrome.
Sex steroids and the X chromosome can independently affect cognitive abilities. Because subjects with Turner syndrome (TS) have gonadal aplasia, and various alterations in X chromosome structure and number, they provide a model to study the effects of sex steroids and of the X chromosome on human brain function. We used neuropsychological tests to study the cognitive abilities of 18 TS adults and 19 age/sex matched healthy controls. Nine TS subjects were mosaic for the 45,X karyotype, and 9 were non-mosaic 45,X (full TS). The TS group as a whole, compared to controls, had (i) significantly lower scores in tests of language and visual-spatial function, attention and memory, and (ii) a significantly greater discrepancy between verbal and performance scores. Mosaic TS subjects were intermediate between full TS and controls in some tests of verbal ability, but did not differ significantly from controls in others. Visuospatial ability was significantly lower than controls in both mosaic and full TS. Within the mosaic TS group, there was a significant negative correlation between visuospatial ability and % lymphocytes having a 45,X karyotype. Memory test scores were reduced independently of "X chromosome dosage" in all TS subjects. We conclude that in humans, the X chromosome is involved in development of both cerebral hemispheres, but moreso of the association neocortices. Also, sex steroids may modulate this effect--particularly in hippocampus.
Adolescent↗
Reduction of functional neuronal connectivity in long-term treated hypertension.
BACKGROUND AND PURPOSE: Anatomic imaging of patients with chronic well-treated hypertension has demonstrated dilatation of the lateral cerebral ventricles and left brain atrophy, whereas positron emission tomography has shown only subtle reductions in regional cerebral metabolic rates for glucose in some subcortical nuclei. To further explore the implications of the imaging changes, an analytic technique designed to determine functional neuronal connectivity between regions of interest (ROIs) was applied to the data on regional cerebral metabolic rates for glucose to determine if and where in the brain reduction of functional neuronal connectivity occurred. METHODS: Glucose metabolism was measured by positron emission tomography in 17 older men (age, 68 +/- 8 years) with well-controlled, noncomplicated hypertension of at least 10 years' duration and in 25 age- and sex-matched healthy control subjects. A significant correlation difference analysis was performed to determine which ROI pairs had reduced correlation coefficients (reduced functional neuronal connectivity). The vascular pattern of the reduction was determined after allocating the ROIs to their appropriate vascular territories. RESULTS: Compared with the control subjects, hypertensive patients had reduced correlation coefficients in cortical territories of the internal carotid arteries but not of the vertebrobasilar arteries. The border zone supplied by the middle and anterior cerebral arteries was most affected. CONCLUSIONS: The border zone between the anterior and middle cerebral arteries is vulnerable to ischemia from carotid pathology, systemic hypotension, or both. We hypothesize that although these hypertensive patients were "well controlled" and had normal neuropsychological tests, they may have experienced ischemia severe enough to cause border zone reduction of functional neuronal connectivity as a result of carotid pathology, antihypertensive medications, hypotensive episodes with a right-shifted autoregulation curve, or other factors in isolation or combination.
Aged↗
Lack of age-related differences in temporal lobe volume of very healthy adults.
PURPOSE: To evaluate age-related differences in temporal and supratemporal brain regions in carefully selected, very healthy men 19 to 92 years of age. METHODS: MR quantification of brain regions used image segmentation into cerebrospinal fluid and brain matter based on nonlinear modeling of pixel intensity distributions. RESULTS: There was a significant age-related decrease (approximately 1% per decade) of posterior frontal lobe volume, but not of temporal lobe volume. The mean volume of the right temporal lobe was significantly greater than the left, and this relation did not change with age. CONCLUSION: In very healthy aging, the volume of the temporal lobes remains constant over the age range of human life.
Adult↗
X-chromosome effects on female brain: a magnetic resonance imaging study of Turner's syndrome.
Many neuropsychiatric disorders differ between the sexes in incidence, symptoms, and age at onset. To investigate the effects of X-chromosome aneuploidy and of sex steroid deficiency during childhood on brain structure and function, we used neuropsychological tests and quantitative magnetic resonance imaging (MRI) to study the brains of eighteen women with Turner's syndrome (TS) and nineteen healthy control women of similar age. Nine TS subjects had mosaic 45,X karyotypes, and 9 had non-mosaic 45,X. The TS group had significantly lower scores than the controls for all the Wechsler adult intelligence scale tests, except verbal comprehension and reading level. The greatest difference was in visuospatial construction (mean 90 [SD12] vs 118 [13], p < 0.0001). The TS subjects also had a greater discrepancy than controls between verbal and performance intelligence quotients (9 [8] vs -5 [9], p < 0.001). We found that TS subjects had significantly smaller values than controls in MRI-measured volumes of hippocampus, caudate, lenticular, and thalamic nuclei, and parieto-occipital brain matter, on both sides. Women with mosaic TS had values between the full TS and control groups for cerebral hemisphere and lenticular and thalamic nuclei volume and for verbal ability. Within the mosaic TS group, visuospatial ability was significantly correlated with the percentage of lymphocytes that had the 45,X karyotype. Hippocampal volume and memory test scores were significantly lower in mosaic and non-mosaic 45,X TS subjects than in controls. We postulate that in human beings the X chromosome plays an important part in the development and ageing of grey matter in striatum, diencephalon, and cerebral hemispheres.
Adult↗
Volumetric magnetic resonance imaging in men with dementia of the Alzheimer type: correlations with disease severity.
Using magnetic resonance imaging (MRI), we measured the volumes of various brain structures and cerebrospinal fluid (CSF) in 19 men with dementia of the Alzheimer type (DAT) and 18 healthy age-matched control men. The mean (+/- S.D) Mini-Mental State exam score (MMSE) of the DAT men was 16 +/- 7; 9 were mildly (MMSE > 20), 5 moderately (MMSE 10-20), and 5 severely (MMSE < 10) demented. Brain and CSF volumes were normalized as a percent of the traced intracranial volume to control for the relation of volumes of cerebral structures to head size, and analyzed statistically. The whole group of DAT subjects had significantly smaller mean cerebral brain matter and temporal lobe volumes (p < 0.05), and significantly larger mean ventricular and temporal lobe peripheral CSF volumes than did controls. Mean volumes of the subcortical nuclei did not differ significantly between groups, and mean volume of temporal lobe brain matter decreased significantly more than whole brain, suggesting regional loss of brain matter in DAT. Mildly demented DAT patients had significantly smaller mean cerebral brain matter and temporal lobe volumes and significantly larger volumes of lateral ventricles, and of temporal lobe peripheral CSF, than did controls. Neuropsychological measures of disease severity in DAT patients were significantly (p < 0.05) and appropriately correlated to volumes of cerebral brain matter and right lateral ventricle. These results suggest that in DAT: (i) significant brain atrophy is present early in the disease process, (ii) brain atrophy correlates with severity of cognitive impairment, and (iii) there is greater involvement of the telencephalic association system than whole brain, and there is relative sparing of the caudate, lenticular and thalamic nuclei.
Aged↗
Aminophylline in the treatment of acute asthma when beta 2-adrenergics and steroids are provided.
BACKGROUND: The purpose of this study was to test the contribution of aminophylline in improving peak expiratory flow rate (PEFR) during emergency department treatment of acute asthma when metaproterenol sulfate and steroid therapy are also provided. METHODS: In a prospective, randomized, double-blind, and placebo-controlled trial at a municipal hospital emergency department, 44 patients with acute asthma, aged 18 to 45 years, with theophylline levels below 28 mumol/L, who had failed to achieve a PEFR of 40% predicted after one nebulized metaproterenol treatment, were recruited. An aminophylline or placebo loading dose and maintenance infusion were administered. All patients received hourly nebulized metaproterenol and initial methylprednisolone sodium succinate. The PEFR was measured hourly for 5 hours. Two-factor repeated-measures analysis of variance of improvement in PEFR ([final-initial PEFR]/predicted PEFR) was assessed. RESULTS: There was no difference in improvement of PEFR at any hour between the treatment and placebo groups. After 5 hours, the difference in improvement ratio was 0.40 (aminophylline) vs 0.36 (placebo) (P = .30; n = 22 in each group). The treatment group suffered more tremor, nausea or vomiting, and palpitations (P < .05). CONCLUSION: In the emergency department setting, aminophylline contributes no significant improvement in PEFR when beta 2-agonists and corticosteroids are being provided, while causing more side effects.
Acute Disease↗
An in vivo study of phosphorus and glucose metabolism in Alzheimer's disease using magnetic resonance spectroscopy and PET.
OBJECTIVES: To study phosphorus and glucose metabolism in whole-brain slices of otherwise healthy patients with dementia of the Alzheimer type (DAT) and healthy controls. DESIGN: We used proton nuclear magnetic resonance imaging phosphorus spectroscopy and positron emission tomography to study in vivo brain phosphorus and glucose metabolism. PATIENTS: Whole-brain slice phosphorus metabolism was studied in nine drug free patients with mild to moderately severe dementia of the Alzheimer type (DAT) and in eight age- and sex-matched healthy controls. Mean ages (+/- SD) of the patients and controls were 60 +/- 10 years and 64 +/- 16 years, respectively. Positron emission tomography was used to study cerebral glucose metabolism in seven of the patients with DAT and seven of the healthy controls. RESULTS: Patients with DAT had significant brain glucose hypometabolism compared with controls, but there was no significant group difference in any phosphorus metabolite concentration or ratio in the same volume of brain tissue. Also, within patients with DAT there was no correlation between any phosphorus metabolite concentration or ratio and either severity of dementia or glucose metabolism. CONCLUSIONS: We suggest glucose metabolism is reduced early in DAT (reflecting decreased basal synaptic functioning) and is unrelated to a rate limitation in glucose delivery, abnormal glucose metabolism, or abnormal coupling between oxidation and phosphorylation. Normal or near-normal levels of phosphorus metabolites are maintained in mild, moderate, and severe DAT. Therefore, altered high-energy phosphate levels are not a consequence of reduced glucose metabolism in DAT, and do not play a major role in the pathophysiology of the disorder, at least in whole-brain sections.
Aged↗
Assessing the diagnostic value of an ECG containing leads V4R, V8, and V9: the 15-lead ECG.
STUDY OBJECTIVES: To assess sensitivity, specificity, and odds ratios of ECG findings on leads V4R, V8, and V9 for acute myocardial infarction. DESIGN: Prospective, two-stage cohort study. SETTING: A 660-bed university-affiliated community hospital. TYPE OF PARTICIPANTS: One hundred forty-nine admitted patients with suspected myocardial infarction or unstable angina. INTERVENTIONS: Standard 12-lead ECG followed immediately by V4R, V8, and V9. MEASUREMENTS: Initial ECG findings of ST-segment displacement, Q waves, T-wave inversion, and eligibility for thrombolytic therapy. RESULTS: Major abnormalities (ST-segment deviation, T-wave inversion, Q waves) were found on the extra three leads in 28.9% (43 of 149) of patients. Sensitivity of ST-segment elevation for acute myocardial infarction on 12 versus 15 leads increased from 47.1% to 58.8%, respectively, with no decrease in specificity. McNemar's pair-matched analysis for ST-segment elevation on myocardial infarction subgroup showed an association of ST elevation with the 15-lead ECG (P < .05). An eightfold increase in the odds of detecting ST elevation was found (90% confidence interval, 1.42 to 14.58); 22% of patients negative for ST elevation on 12 leads were positive on 15 leads. Analysis of ECG criteria for thrombolytic therapy presenting uniquely on extra leads showed an increased sensitivity from 35.3% to 44.1% on 12 versus 15 leads, respectively; there was a sixfold increase in the odds of meeting ECG thrombolytic therapy criteria (90% confidence interval, 0.34 to 11.66); 13.5% of patients not meeting criteria on 12 leads did so on 15 leads. CONCLUSION: The 15-lead ECG provides increased sensitivity and odds of detecting ST-segment elevation in acute myocardial infarction patients with no loss of specificity; its use may expand the selection of thrombolytic therapy candidates and provide a fuller ECG description of the extent of myocardial injury and necrosis.
Aged↗
Seasonal affective disorder: response to light as measured by electroencephalogram, melatonin suppression, and cerebral blood flow.
This study was designed to test the hypothesis that patients with SAD have significantly different physiological responses to light than healthy age- and sex-matched controls. We studied retinal contrast sensitivity, visual evoked EEG responses, and melatonin suppression by, and cerebral blood flow response to, full-spectrum artificial daylight. There was no significant difference between 10 patients and 11 controls in retinal contrast sensitivity, or amplitude or latency of N2, P2, P100 or P300 on EEG. We compared melatonin suppression in 12 SAD patients and 12 controls. During exposure to 500 lux and 1500 lux artificial daylight both the SAD patients and controls had a significant melatonin percentage suppression; however, the percentage suppression did not differ significantly between the SAD patients and the controls. In addition, we carried out a small pilot study into the effect of light on cerebral blood flow in four SAD patients and four controls. Before exposure to 1500 lux artificial daylight there was no significant difference between patients and controls in global, regional or cerebral hemispheric blood flow. After light exposure the SAD patients and controls had a significantly different percentage change in cerebral blood flow. We suggest that patients with SAD do not have significantly physiological responses to light than controls, except perhaps in cerebral blood flow. Furthermore, mechanisms other than supersensitivity of melatonin suppression must explain both the pathophysiology of the disorder and its response to treatment with light.
Bipolar Disorder↗
Melatonin rhythms in seasonal affective disorder.
We examined 24-hour melatonin rhythms from 20 patients with seasonal affective disorder (SAD) and 20 healthy volunteers. Patients and controls were individually matched for age, sex, and month of study. Plasma samples were taken at hourly intervals, and were assayed for melatonin by radio-immunoassay. The 24-hourly melatonin estimations for each individual were fitted to a cosine curve, and the significance of the curve fits was calculated. Two analyses were performed. In analysis 1 the following were calculated: (a) cosine fit, (b) significance of fits, (c) mean amplitude and acrophase (peak) and (d) mean melatonin levels. The curve fits were highly significant for all but three subjects (two patients, one control), but there were no significant differences in any measure between the two groups. In analysis 2 the comparisons were repeated and restricted to the 18 patients and 19 controls in whom there was a significantly significant melatonin rhythm. Again there were no significant differences between groups. These results suggest that the circadian rhythm of melatonin is not abnormal in SAD, and that the therapeutic effect of light in SAD is not mediated by phase shifts in melatonin secretion.
Adult↗
Age-related differences in volumes of subcortical nuclei, brain matter, and cerebrospinal fluid in healthy men as measured with magnetic resonance imaging.
Magnetic resonance imaging was used to determine the volumes of brain, subcortical gray matter nuclei, and the ventricular and sulcal cerebrospinal fluid in 27 healthy men. Subjects were divided into young (less than 35 years, n = 10) and old (greater than 60 years, n = 17) groups. Volumes were normalized as percent intracranial volume. Older subjects had significantly less brain mass and significantly larger ventricular and peripheral cerebrospinal fluid volumes than the younger men. The caudate and lenticular nuclei were significantly smaller in older than younger men. This significant difference remained when their volumes were expressed as a ratio of cerebral brain matter volume. This cross-sectional study demonstrates age-related atrophy and concurrent dilation of cerebrospinal fluid spaces in healthy subjects. Of brain regions affected, the caudate and lenticular nuclei are significantly more affected by healthy aging than is cerebral brain matter; this may account for some of the motor abnormalities in aging.
Adult↗
Brain atrophy in hypertension. A volumetric magnetic resonance imaging study.
To determine whether hypertension, the predominant risk factor for stroke and vascular dementia, is associated with brain atrophy, magnetic resonance imaging (MRI) scans were performed to quantify brain volumes and cerebrospinal fluid spaces. Eighteen otherwise healthy, cognitively normal older hypertensive men (mean +/- SD age, 69 +/- 8 years, duration of hypertension 10-35 years) and 17 age-matched healthy, normotensive male control subjects were studied in a cross-sectional design. Axial proton-density image slices were analyzed using region-of-interest and segmentation analyses. The hypertensive subjects had significantly larger mean volumes of the right and left lateral ventricles (p less than 0.05, both absolute volume and volume normalized to intracranial volume) and a significantly smaller normalized mean left hemisphere brain volume (p less than 0.05) with a trend toward significance for a smaller normalized mean right hemisphere volume (p less than 0.09). Four hypertensive subjects and one healthy control subject were found to have severe periventricular hyperintensities on T2-weighted MRI images. When data for these subjects were removed from the analyses, the normalized lateral ventricle volumes remained significantly larger in the hypertensive group. Lateral ventricle enlargement was not related to age or use of diuretics in the hypertensive group nor to duration of hypertension between 10 and 24 years. Our findings suggest that long-standing hypertension results in structural changes in the brain. Longitudinal studies will determine whether MRI-associated changes are progressive and if such changes identify hypertensive subjects at increased risk for clinically apparent brain dysfunction.
Adult↗
Conservative soft tissue management with the low-powered pulsed Nd:YAG dental laser.
Lasers can be operated in a continuous or pulsed mode, either in contact or out of contact with the target tissue. This article discusses laser systems and their resultant effects, and presents histologic findings and clinical examples.
Adolescent↗
Numerous transitions in human parainfluenza virus 3 RNA recovered from persistently infected cells.
The nucleotide sequences at the 3'-termini of human parainfluenza virus 3 (HPIV3) genomic RNAs recovered from two lines of persistently infected LLC-MK2 cells were determined following PCR amplification. After 29 months of persistence the 3'-end of the HPIV3 genome was found to be highly mutated. Interestingly, the only types of nucleotide changes observed were U to C and A to G transitions. Both U to C and A to G transitions were present on individual RNA molecules. The data indicate that biased hypermutational activity leading to U To C and A to G mutations operates in cultured cells during persistent HPIV3 infections.
Base Sequence↗
Tension pneumothorax associated with hyperbaric oxygen therapy.
The authors present three patients who developed a tension pneumothorax while receiving emergent hyperbaric oxygen therapy for acute carbon monoxide poisoning. Each patient was intubated and received closed chest compressions for cardiac arrest prior to hyperbaric oxygenation. Despite the apparent absence of pneumothorax prior to hyperbaric therapy, tension pneumothorax was detected soon after decompression. These cases illustrate the need for vigilance in detecting and addressing pneumothorax prior to hyperbaric decompression in obtunded patients. Serial physical examinations, arterial blood gas determinations, properly positioned chest radiographs, and a high index of suspicion for pneumothorax in the setting of emergent hyperbaric therapy are recommended.
Adolescent↗
The classification and treatment of dysthymia.
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Adolescent↗
Viral RNA and protein synthesis in two LLC-MK2 cell lines persistently infected with human parainfluenza virus 3.
Two lines of LLC-MK2 cells persistently infected with human parainfluenza virus 3 (HPIV-3) have been maintained in culture for approximately 3 years. Subgenomic RNAs (putative defective interfering particle genomes) were detected in virions released from both persistently infected cultures. In one of the persistently infected cell lines cyclic variation in the production of virions containing standard virus genomic-size (50S) RNA and subgenomic RNA was observed. The molar ratio of subgenomic RNA to 50S RNA ranged from less than 0.1/1 to 8.7/1. Northern blot analyses revealed that the patterns of viral mRNA synthesis in persistently infected cells from both cultures were similar to those of standard virus infected cells. Furthermore, the intracellular viral-specific proteins had electrophoretic mobilities similar to the corresponding proteins in standard virus-infected cells. Nucleotide sequence analysis of cloned M gene from virus after 29 months of persistence (147 passages) revealed only one variable conservative amino acid change in two clones analyzed from each cell line, indicating that the M protein is not likely to be involved in the maintenance of the persistent infections. The possible mechanisms by which the persistent state is maintained are discussed.
Cell Line↗