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Biomedical subjects

D G Murphy

Publications and source records attributed to D G Murphy.

At least 37 records · Page 2Linked to original sources

Volumes of medial temporal lobe structures in patients with Alzheimer's disease and mild cognitive impairment (and in healthy controls).

BACKGROUND: The clinical diagnosis of Alzheimer's disease (AD) can be difficult to make in early stages of disease. Structural neuroimaging offers a potential tool in the clinical diagnosis of AD with mild cognitive impairment. Postmortem studies indicate that early neuropathology in AD occurs in medial temporal lobe limbic structures. Magnetic resonance imaging (MRI) studies that assessed these volumes in mildly impaired AD patients remain inconclusive. METHODS: Using MRI, we measured volumes of left and right hippocampus, amygdala, and anterior and posterior parahippocampal gyrus (PHG) in 13 AD patients with mild cognitive impairment, defined as > or = 20 on the Mini-Mental State Exam, and in 21 healthy age- and sex-matched controls. RESULTS: The AD patients had smaller medial temporal lobe volumes, except for the right anterior PHG. Discriminant function analysis using MRI volumes produced 94% correct group classification. CONCLUSIONS: These results show that in mildly impaired AD patients atrophy is present in medial temporal lobe structures; that MRI volumes of the anterior PHG, which contains entorhinal cortex, are reduced, but the amygdala and hippocampal volumes show greater reduction; and that discriminant function analysis using all volumes as predictors can correctly classify a high proportion of individuals.

Aged↗

Prediction of relapse within eight weeks after an acute asthma exacerbation in adults.

Associations between historical, presenting, and treatment-related characteristics and relapse within 8 weeks after a moderate to severe asthma exacerbation were studied in a cohort of 284 adult asthmatics. Data were collected prospectively, and a multivariate model was developed and internally validated. Within 10 days, only 8% had relapsed, increasing to 45% by 8 weeks. Three variables that could be identified at the time of discharge were independently associated with relapse. These included: having made three or more visits to an emergency department in the prior 6 months (hazard ratio (HR) = 2.3, 95% CI = 1.6-3.4); difficulty performing work or activities as a result of physical health in the 4 weeks prior (HR = 2.7, 95% CI = 1.6-4.3); discontinuing hospital-based treatment for the exacerbation within 24 hours without having achieved a peak expiratory flow rate of at least 50% of predicted (HR = 2.6, 95% CI = 1.6-4.1). These risk factors may help to identify patients with poorly controlled asthma in need of more intensive and comprehensive management.

Acute Disease↗

Emergency Department Observation Unit versus hospital inpatient care for a chronic asthmatic population: a randomized trial of health status outcome and cost.

OBJECTIVES: This study was designed to determine if an accelerated treatment protocol administered to acute asthmatics presenting to a Hospital Emergency Department Observation Unit (EDOU) can offset the need for inpatient admissions and reduce total cost per episode of care without sacrificing patient quality of life. METHODS: The authors used a prospective randomized controlled trial comparing postintervention patient quality of life for EDOU care versus standard inpatient care as measured by the standardized Medical Outcomes Study (MOS) SF-36 instrument. Other measures reported include: clinical status as measured by peak flow rates, total cost per treatment arm using microcosting techniques, and relapse-free survival 8 weeks after treatment. Eligible patients (n = 113) were assigned randomly to an EDOU or inpatient care from a consecutive sample of 250 acute asthmatic patients presenting to an urban hospital emergency department who could not resolve their acute asthma exacerbation after 3 hours of emergency department therapy. RESULTS: Patients assigned to the EDOU had lower mean costs of treatment (EDOU = $1,202 versus Hospital Inpatient = $2,247) and higher quality of life outcomes after intervention in five of eight domains measured by the MOS SF-36: Physical Functioning, Role Functioning-Emotional, Social Functioning, Mental Health, and Vitality. No differences were found in clinical outcomes as measured by peak flow rates or postintervention relapse-free survival. Univariate comparative findings were re-examined and confirmed through multivariable analysis when baseline SF-36 scores and postintervention peak expiratory flow rates clinical status were used as covariates. CONCLUSIONS: The study showed that the EDOU was a lower cost and more effective treatment alternative for a refractory asthmatic population presenting to the Emergency Department. Several baseline MOS SF-36 domains proved useful in predicting or validating posttreatment clinical status, relapse, and total costs of care. Outcome SF-36 domain scores were also useful in identifying patients with the most favorable clinical, cost, and relapse rate outcomes at the study endpoint.

Adolescent↗

Costs of an emergency department-based accelerated diagnostic protocol vs hospitalization in patients with chest pain: a randomized controlled trial.

CONTEXT: More than 3 million patients are hospitalized yearly in the United States for chest pain. The cost is over $3 billion just for those found to be free of acute disease. New rapid diagnostic tests for acute myocardial infarction (AMI) have resulted in the proliferation of accelerated diagnostic protocols (ADPs) and chest pain observation units. OBJECTIVE: To determine whether use of an emergency department (ED)-based ADP can reduce hospital admission rate, total cost, and length of stay (LOS) for patients needing admission for evaluation of chest pain. DESIGN: Prospective randomized controlled trial comparing admission rate, total cost, and LOS for patients treated using ADP vs inpatient controls. Total costs were determined using empirically measured resource utilization and microcosting techniques. SETTING: A large urban public teaching hospital serving a predominantly African American and Hispanic population. PATIENTS: A sample of 165 patients was randomly selected from a larger consecutive sample of 429 patients with chest pain concurrently enrolled in an ADP diagnostic cohort trial. Eligible patients presented to the ED with clinical findings suggestive of AMI or acute cardiac ischemia (ACI) but at low risk using a validated predictive algorithm. MAIN OUTCOME MEASURES: Primary outcomes measured for each subject were LOS and total cost of treatment. RESULTS: The hospital admission rate for ADP vs control patients was 45.2% vs 100% (P<.001). The mean total cost per patient for ADP vs control patients was $1528 vs $2095 (P<.001). The mean LOS measured in hours for ADP vs control patients was 33.1 hours vs 44.8 hours (P<.01). CONCLUSIONS: In this trial, ADP saved $567 in total hospital costs per patient treated. Use of ED-based ADPs can reduce hospitalization rates, LOS, and total cost for low-risk patients with chest pain needing evaluation for possible AMI or ACI.

Adult↗

A comparison between emergency diagnostic and treatment unit and inpatient care in the management of acute asthma.

BACKGROUND: Emergency diagnostic and treatment units (EDTUs) may provide an alternative to hospitalization for patients with reversible diseases, such as asthma, who fail to adequately respond to emergency department therapy. OBJECTIVE: To evaluate the medical and cost-effectiveness, patient satisfaction, and quality of life of patients receiving EDTU care for acute asthma compared with inpatient care. METHODS: A prospective, randomized clinical trial performed at 2 urban public hospitals enrolled patients with acute asthma (age range, 18-55 years) not meeting discharge criteria after 3 hours of emergency department therapy. Patients were treated with inhaled adrenergic agonists and steroids in an EDTU for up to 9 hours after randomization or with routine therapy in a hospital ward. Patients were followed up for 8 weeks. MAIN OUTCOME MEASURES: Discharge rate from the EDTU, length of stay, relapse rates, days missed from work or school, days incapacitated during waking hours, symptom-free days and nights, nocturnal awakenings, direct medical costs, patients satisfaction, and patient quality of life. RESULTS: The study consisted of 222 patients with asthma. Sixty-five patients (59%) treated in an EDTU were discharged home; the remainder were admitted to the hospital. There were no differences during the follow-up period in relapse rates (P = .74) or in any other morbidities between the EDTU and inpatient groups. There were significant differences in the length of stay, patient satisfaction, and quality of life favoring EDTU care. The mean (+/-SD) cost per patient in the EDTU group was $1202.79 +/- $1343.96, compared with $2247.32 +/- $1110.18 for the control group (P < .001). CONCLUSIONS: Treatment of selected patients with asthma in an EDTU results in the safe discharge of most such patients. This study suggests that quality gains and cost-effective measures can be achieved by the use of such units.

Acute Disease↗

A PET study of Turner's syndrome: effects of sex steroids and the X chromosome on brain.

Women with Turner's syndrome (TS) allow us to study the neurobiological associates of cognitive and behavioral abnormalities because they lack one/part of one X chromosome, and endogenous estrogen. We studied 13 healthy controls (mean age +/- SD, 28 +/- 6 years) and 16 TS subjects (mean age +/- SD, 26 +/- 6 years). We measured cognitive abilities using neuropsychological tests, and cerebral metabolic rates for glucose with positron emission tomography. Compared to controls, TS subjects had significant absolute hypermetabolism in most brain areas; however, normalized metabolism was significantly lower in TS subjects than controls in the insula and association neocortices bilaterally, and there were significant differences in functional metabolic associations of brain region pairs originating in occipital cortex bilaterally, and within the right hemisphere. There were significant correlations between right-left cognitive and metabolic asymmetries in the TS group. Also, within TS a preliminary analysis demonstrated "X chromosome dosage" effects in language ability and left temporal metabolism, asymmetry of right-left test scores, and parietal metabolism. We hypothesize that within TS: i) generalized brain hypermetabolism reflects global abnormalities in neuron packing; ii) neuronal abnormalities occur in association neocortex that differ in nature or extent from whole brain and are associated with significant differences in normalized metabolism; iii) cognitive deficits are related to brain metabolic abnormalities; and iv) social-behavioral problems may be related to abnormalities of brain metabolism. Moreover, in human brain the X chromosome involved in development of the association neocortices.

Adult↗

Sex differences in human brain morphometry and metabolism: an in vivo quantitative magnetic resonance imaging and positron emission tomography study on the effect of aging.

BACKGROUND: There are significant age and sex effects in cognitive ability and brain disease. However, sex differences in aging of human brain areas associated with nonreproductive behavior have not been extensively studied. We hypothesized that there would be significant sex differences in aging of brain areas that subserve speech, visuospatial, and memory function. METHODS: We investigated sex differences in the effect of aging on human brain morphometry by means of volumetric magnetic resonance imaging and on regional cerebral metabolism for glucose by positron emission tomography. In the magnetic resonance imaging study, we examined 69 healthy right-handed subjects (34 women and 35 men), divided into young (age range, 20 to 35 years) and old (60 to 85 years) groups. In the positron emission tomography study, we investigated 120 healthy right-handed subjects (65 women and 55 men) aged 21 to 91 years. RESULTS: In the magnetic resonance imaging study, age-related volume loss was significantly greater in men than women in whole brain and frontal and temporal lobes, whereas it was greater in women than men in hippocampus and parietal lobes. In the positron emission tomography study, significant sex differences existed in the effect of age on regional brain metabolism, and asymmetry of metabolism, in the temporal and parietal lobes, Broca's area, thalamus, and hippocampus. CONCLUSIONS: We found significant sex differences in aging of brain areas that are essential to higher cognitive functioning. Thus, our findings may explain some of the age-sex differences in human cognition and response to brain injury and disease.

Adult↗

Biological and clinicopathological features associated with hepatitis C virus type 5 infections.

BACKGROUND/AIMS: The biological and clinicopathological features of hepatitis C virus infections of type 1 and type 2 have been well documented. However, little is known about the nature of HCV type 5 infections, which have been found to occur in South Africa but rarely elsewhere. METHODS: We investigated the HCV genotypes in 125 viremic blood donors and 125 viremic patients by restriction endonuclease analysis of amplified 5' non-coding region sequences. Donors and patients infected with type 5 were further studied. Serum HCV RNA levels were assessed by a differential-size PCR-aided transcript titration assay. RESULTS: HCV type 5 infections were identified in seven (5.6%) of the blood donors and in five (4.0%) of the patients. Sera from these 12 persons reacted with the core and NS3 antigens in both RIBA-2 and RIBA-3 tests. Six (50%) and 10 (83%) sera reacted with the NS4 antigens in RIBA-2 and RIBA-3 tests, respectively. HCV type 5 was found to replicate to high titers that ranged from 10(6.0) to 10(8.0) molecules/ml. Transfusion was the most frequently observed risk factor (5 of 12) and persons infected with type 5 were generally older than those infected with other types (< 40 years vs. > or = 40 years, p = 0.01). Cirrhosis was found in two of six (33%) donors and three of four (75%) patients. The duration of infection appeared to be an important determinant for the presence of cirrhosis. CONCLUSIONS: In this small group of Canadians infected with HCV type 5, a high proportion developed severe liver disease.

Adult↗

The emergency department electrocardiogram and hospital complications in myocardial infarction patients.

OBJECTIVE: To determine whether acute myocardial infarction (AMI) patients who have negative ECGs on presentation have significantly lower complication rates than do those AMI patients who have positive ECGs on presentation. METHODS: Retrospective, cohort analysis comparing rates of hospital complications (ventricular fibrillation or tachycardia, shock, atrial arrhythmia or bradyarrhythmia with systolic blood pressure < or = 90 mm Hg, pulmonary edema) or interventions among patients with a final hospital diagnosis of AMI and an initially negative vs positive ECG. A negative ECG was normal or had nonspecific ST-segment and/or T-wave abnormalities (upright, flattened T waves; an isolated inverted T wave; ST depression < 0.1 mV; tall T waves with J-point elevation) or minor nonischemic abnormalities. Sample size was adequate to detect a 30% between-group difference in complication rates [alpha = 0.05, 1 - beta (power) = 0.80]. RESULTS: The 27 negative-ECG AMI patients differed from the 38 control patients in (mean +/- SD) age [57 +/- 12 vs 66 +/- 12 years, p < 0.01] but not in gender or history of AMI. The negative- and positive-ECG groups had similar rates of hospital complications [30% (95% CI: 13-47%) vs 42% (95% CI: 26-58%), p = 0.44] and intensive procedures [19% (95% CI: 4-34%) vs 29% (95% CI: 15-43%), p = 0.50], respectively. The negative-ECG patients with hospital complications had ECG evolution precede the event in 83% (95% CI: 69-97%) of cases; persistently negative-ECG patients had no complications [(95% CI: 0-33%), p = 0.06]. CONCLUSIONS: Negative- and positive-ECG AMI patients do not have moderate or large differences in the rates of in-hospital complications. Most negative-ECG patients who suffer complications evolve ECG changes prior to the event and such changes indicate the potential need for a higher level of care.

Adult↗

Identification of numerous hepatitis C virus genotypes in Montreal, Canada.

Hepatitis C virus genotypes were determined for 358 viremic individuals in Montreal, Canada, by restriction endonuclease analysis of PCR products and phylogenetic analysis of core gene sequences. Types 1, 2, and 3 occurred in 62.8, 14.2, and 13.7%, respectively; types 4 and 5 were found in 3.9 and 4.5%, respectively; and genotypes 6a and 7c and a novel genotype each occurred in 0.3%. Types 4, 6, and 7 and the novel genotype were mostly from persons who had immigrated to Canada.

Adult↗

Comparison of positron emission tomography, cognition, and brain volume in Alzheimer's disease with and without severe abnormalities of white matter.

OBJECTIVES: To examine cerebral metabolism, cognitive performance, and brain volumes in healthy controls and two groups of patients with probable Alzheimer's disease, one group with severe abnormalities of white matter (DAT+) and the other group with none, or minimal abnormalities (DAT-). METHODS: Neuropsychological tests, CT, MRI, quantitative MRI, and PET studies were carried out to allow comparison between the DAT+ and DAT- groups and the healthy controls. RESULTS: Compared with the healthy controls, both demented groups had significantly reduced global and regional cerebral metabolism, significant brain atrophy, and significantly lower scores on neuropsychological testing. The DAT- patient group showed a pattern of parietal-temporal cerebral metabolic reductions and neuropsychological performance deficits typical of Alzheimer's disease. In addition, metabolism in the association neocortex (AD ratio) and measures of neuropsychological task performance were significantly correlated in the DAT- patient group. Comparison of DAT+ with DAT- patients showed a significantly higher ratio of parietal to whole brain glucose utilisation for the DAT+ group. Moreover, when comparing group z score differences from the healthy controls, the DAT+ group had, on average, smaller differences from controls in the frontal, parietal, and temporal regions than did the DAT- group. Discriminant analysis using metabolic ratios of the frontal, parietal, and temporal regions showed cerebral metabolic patterns to be significantly different among the DAT+, the DAT-, and the healthy controls. These differences were due primarily to relatively higher frontal, parietal, and temporal metabolic ratios in the DAT+ group which resulted in discriminant scores for the DAT+ group between the healthy controls and the DAT- group. Group mean scores on tests of neuropsychological performance were not significantly different between the DAT- and DAT+ patients. By contrast with the DAT- group, however, no significant correlations between the AD ratio and any neuropsychological task were seen in the DAT+ group. Multiple regression analysis showed significant between group differences in the relation between the AD ratio and neuropsychological scores on three tasks. The slopes of the relations between the AD ratio and memory scores (memory and freedom from distractability deviation quotient of the Wechsler adult intelligence scale (WMDQ)) also were significantly different for the two groups. CONCLUSIONS: Although multiple causes for abnormalities of white matter exist in patients with Alzheimer's disease, these data suggest that the presence of severe abnormalities of white matter indicate a second pathological process in the DAT+ patients. The DAT- patients showed the parietal-temporal metabolic deficits and correlations between association neocortical metabolism and neuropsychological task performance typical of patients with Alzheimer's disease. By contrast, the DAT+ group had a pattern of cerebral metabolism significantly different from healthy controls and DAT+ patients, as well as no significant correlations between metabolism in the association neocortex and neuropsychological performance. These differences probably reflect the superimposed pathology of the abnormalities of white matter which may exert their affect through disruption of long corticocortical pathways.

Aged↗

Adult fragile X syndrome: neuropsychology, brain anatomy, and metabolism.

To understand the implications of suboptimal gene expression in fragile X syndrome -fra(X)-, we sought to define the central nervous abnormalities in fra(X) syndrome to determine if abnormalities in specific brain regions or networks might explain the cognitive and behavioral abnormalities in this syndrome. Cranial and ventricular volumes were measured with quantitative computed tomography (CT), regional cerebral metabolic rates for glucose (rCMRglc) were measured with [18-F]-2-fluoro-2-deoxy-D-glucose (18FDG), and patterns of cognition were determined with neuropsychological testing in ten healthy, male patients with karyotypically proven fra(X) syndrome (age range 20-30 yr). Controls for the CT studies were 20 healthy males (age range 21-37 yr), controls for the PET studies were 9 healthy males (age range 22-31 yr), and controls for the neuropsychological tests were 10 young adult, male Down syndrome (DS) subjects (age range 22-31 yr). The mean mental age of the fra(X) syndrome group was 5.3 yr (range 3.5-7.5 yr; Stanford-Binet Intelligence Scale). Despite comparable levels of mental retardation, the fra(X) subjects showed poorer attention/short term memory in comparison to the DS group. Further, the fra(X) subjects showed a relative strength in verbal compared to visuospatial attention/short term memory. As measured with quantitative CT, 8 fra(X) subjects had a significant (P < 0.05) 12% greater intracranial volume (1,410 +/- 86 cm3) as compared to controls (1,254 +/- 122 cm3). Volumes of the right and left lateral ventricles and the third ventricle did not differ between groups. Seven of eight patients had greater right lateral ventricle volumes than left, as opposed to 9 out of 20 controls (P < 0.05). Global gray matter CMR-glc in nine fra(X) patients was 9.79 +/- 1.28 mg/100 g/minute and did not differ from 8.84 +/- 1.31 mg/100 g/minute in the controls. R/L asymmetry in metabolism of the superior parietal lobe was significantly higher in the patients than controls. A preliminary principal component analysis of metabolic data showed that the fra(X) subjects tended to form a separate subgroup that is characterized by relative elevation of normalized metabolism in the lenticular nucleus, thalamus, and premotor regions. Further, a discriminant function, that reflected rCMRglc interactions of the right lenticular and left premotor regions, distinguished the fra(X) subjects from controls. These regions are part of a major group of functionally and anatomically related brain regions and appear disturbed as well in autism with which fra(X) has distinct behavioral similarities. These results show a cognitive profile in fra(X) syndrome that is distinct from that of Down syndrome, that the larger brains in fragile X syndrome are not accompanied by generalized cerebral cortical atrophy or hypoplasia, and that distinctive alterations in resting regional glucose metabolism, measured with 18 FDG and PET, occur in fra(X) syndrome.

Adult↗

Abnormal brain glucose metabolism in the delusional misidentification syndromes: a positron emission tomography study in Alzheimer disease.

Brain lesions have been reported with increasing frequency in the delusional misidentification syndromes (DMS). This is the first controlled study to describe DMS regional cerebral metabolic rates of glucose (rCMRglc). We compared rCMRglc (using positron emission tomography) and neuropsychological data in 9 patients with DMS and Alzheimer dementia (AD), 15 AD patients without DMS, and 17 healthy controls. The DMS group differed from the AD group without DMS in having significant hypometabolism in paralimbic (orbitofrontal and cingulate areas bilaterally) and left medial temporal areas, and significant bilateral normalized hypermetabolism in sensory association cortices (superior temporal and inferior parietal) without right left asymmetry. Compared to healthy controls, both AD groups had significant dorso lateral frontal hypometabolism bilaterally. No specific DMS neuropsychological profile was identified. Dysfunctional connections among multimodal association areas, paralimbic structures, and dorsolateral frontal cortex are proposed as the predisposing neural deficit underlying DMS, causing cognitive-perceptual-affective dissonance, which under specific conditions results in "positive" delusion formation.

Aged↗

Discriminant analysis of MRI measures as a method to determine the presence of dementia of the Alzheimer type.

Multivariate discriminant analysis of brain volumes obtained from semiautomated magnetic resonance image (MRI) quantification was used in an attempt to identify demented patients very early in the course of the disease. Temporal and posterior frontal brain volumes were quantified from MRIs in a cross-sectional study of 31 male and female patients with dementia of the Alzheimer type (DAT) and 29 age- and sex-matched healthy comparison subjects. Mean scores on the Folstein Mini-Mental State Examination (MMS) were in the mild range for the DAT group (20 +/- 6.6), but patients with moderate and severe dementia were also included (MMS range of entire DAT group = 4-28). Significant mean differences in frontal and temporal lobe brain volumes were found between the DAT group and the age- and sex-matched healthy comparison group, but the sensitivity of any single measure was limited to 87% with a specificity of 83%. Initial multivariate discriminant analysis revealed significant gender differences among the healthy subjects, but not the DAT patients. The large group size allowed for subsequent discriminant analyses to be performed by gender. All healthy subjects and DAT patients were correctly classified by gender-specific discriminant functions. The male discriminant variables included brain volume, age, and temporal lobe measures. Inclusion of age in the male discriminant function accounted for age-related brain atrophy, a finding that may have emerged as a consequence of the broad age range of the male DAT population (50-81 years). The male discriminant function was also successfully applied to an independent group of mildly demented subjects that included patients for whom the diagnosis of dementia was uncertain but verified by follow-up clinical evaluations. Measures of temporal lobe brain matter and temporal lobe cerebrospinal fluid volumes were the significant discriminator variables for the women. Quantitative MRI and multivariate discriminant analysis showed promise in distinguishing the dementing process from healthy aging in a group of 60 subjects. Moreover, while not diagnostic of DAT, the approach appeared to offer additional information about the probability of a diagnosis being later confirmed in patients with very mild dementia for whom the clinical identification of DAT is uncertain.

Adult↗

Can a day 4 bone scan accurately determine the presence or absence of scaphoid fracture?

STUDY OBJECTIVE: To evaluate the accuracy of day 4 bone scans in predicting the presence or absence of fracture in patients with "clinical scaphoid fracture." DESIGN: Prospective sensitivity study of ED patients with clinical scaphoid fractures. Each patient was immobilized in a thumb spica cast and had day 4 bone scans of both wrists and hands. Blinded day 4 bone scan results were ultimately compared with the diagnosis on day 14 when patients returned for repeat clinical examination and radiographs. In cases of equivocal radiographic or clinical examination results, a day 14 bone scan was performed. SETTING: Two tertiary care teaching hospital emergency departments. PARTICIPANTS: All ED patients older than 16 years with the diagnosis of clinical scaphoid fracture were eligible. RESULTS: Ninety-nine patients were enrolled and successfully completed the study protocol from October 1990 through November 1992. One patient had bilateral injury, for a total of 100 completed studies. Day 4 bone scans were 100% sensitive and 92% specific, for a positive predictive value of 65%, a negative predictive value of 100%, and accuracy of 93% (95% confidence interval, 88%, to 98%). Many other types of fractures were identified on the day 4 scans, including those of the triquetra, distal radius, capitate, hamate, trapezoid, trapezium, and metacarpals. CONCLUSION: Day 4 bone scans are an accurate means of ruling out scaphoid fracture. However, because of a significant number of false-positive scans at day 4, they do not reliably confirm the diagnosis of scaphoid fracture. The bone scans also permitted identification of several other wrist fractures that had not been radiographically apparent.

Adolescent↗

The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults.

OBJECTIVE: To assess the association of MRI white matter hyperintensities (WMHI) with cognitive performance, cerebral structure, and cerebral metabolism in 51 healthy individuals aged 19 to 91 years without cerebrovascular risk factors. BACKGROUND: Abnormal white matter signals have been associated with brain atrophy, reduced cerebral blood flow, focal neurologic signs, gait disorder, and poorer neuropsychological test performance. Most studies of WMHI, however, include subjects with hypertension or other identifiable causes of cerebrovascular disease that may have an independent effect on brain structure and function. To assess brain changes associated with WMHI independent of cerebrovascular risk factors, we determined WMHI volume, brain volume, cerebral metabolism, and cognitive performance for a group of subjects free of medical illness. Regional cerebral metabolism and cognitive domains were also assessed to evaluate the possible role of frontal lobe dysfunction in subjects with WMHI. DESIGN: Cross-sectional study of 51 very healthy subjects aged 19 to 91 years. METHODS: WMHI, brain, and CSF volumes were determined by MRI segmentation. Neuropsychological tests were employed to assess multiple cognitive domains. Brain metabolism was determined from 18-fluoro-2-deoxy-D-glucose PET. Multivariate relations were tested with stepwise linear regression. Models included the potential confounders of age and education where appropriate. RESULTS: The distribution of WMHI volume was bimodal, with five subjects having WMHI volumes beyond three SDs from the normally distributed population. A WMHI volume of greater than 0.5% of intracranial volume was considered abnormal. Within the multivariate models, WMHI volumes were significantly predictive of increased ventricular volume, reduced brain volume, and reduced cognitive scores. Subjects with greater than 0.5% WMHI volume also had significantly lower frontal lobe metabolism, significantly higher systolic blood pressure, significantly larger ventricular volume, and significantly lower scores on frontal lobe-mediated neuropsychological tests than age-matched controls. CONCLUSION: WMHI volume is associated with structural and functional brain changes even within a group of very healthy individuals. WMHI is associated with poorer frontal lobe cognitive function and, when severe, is accompanied by significantly reduced frontal lobe metabolism. Subjects with large WMHI volumes have significantly higher systolic blood pressure, brain atrophy, reduced cerebral metabolism, and lower scores on tests of frontal lobe function than age-matched controls. Large amounts of WMHI are, therefore, pathologic and may be related to elevated systolic blood pressure even when it is within the normal age-related range.

Adult↗

Sex differences in patterns of hemispheric cerebral metabolism: a multiple regression/discriminant analysis of positron emission tomographic data.

Sex differences in brain hemispheric structure and function have been reported, and sex-related differences in hemispheric interregional correlations were reported in a prior analysis of resting PET glucose metabolic (rCMRglc) data. To explore further the effect of sex on patterns of hemispheric brain functional interactions, we applied a multiple regression/discriminant analysis to resting rCMRglc PET data from young normal men and women to test two hypotheses: (1) women have stronger between-hemisphere functional interactions; (2) men have stronger within-hemisphere functional interactions. Two separate discriminant functions based on these hypotheses distinguished men and women: the first reflected rCMRglc interdependencies between hemispheres and correctly classified all women and 94% of the men; the second reflected rCMRglc interdependencies within the left hemisphere and correctly classified 82% of the women and 88% of the men. Because the discriminant functions successfully distinguished men and women, these results provide support for both hypotheses.

Adult↗