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Biomedical subjects

J P Miller

Publications and source records attributed to J P Miller.

At least 19 recordsLinked to original sources
PubMed2006

PM2.5 constituents and related air quality variables as predictors of survival in a cohort of U.S. military veterans.

Air quality data on trace metals, other constituents of PM2.5, and criteria air pollutants were used to examine relationships with long-term mortality in a cohort of male U.S. military veterans, along with data on vehicular traffic density (annual vehicle-miles traveled per unit of land area). The analysis used county-level environmental data for the period 1997-2002 and cohort mortality for 1997-2001. The proportional hazards model included individual data on age, race, smoking, body mass index, height, blood pressure, and selected interactions; contextual variables also controlled for climate, education, and income. In single-pollutant models, traffic density appears to be the most important predictor of survival, but potential contributions are also seen for NO2, NO3-, elemental carbon, nickel, and vanadium. The effects of the other main constituents of PM2.5, of crustal particles, and of peak levels of CO, O3, or SO2 appear to be less important. Traffic density is also consistently the most important environmental predictor in multiple-pollutant models, with combined relative risks up to about 1.2. However, from these findings it is not possible to discern which aspects of traffic (pollution, noise, stress) may be the most relevant to public health or whether an area-based predictor such as traffic density may have an inherent advantage over localized measures of ambient air quality. It is also possible that traffic density could be a marker for unmeasured pollutants or for geographic gradients per se. Pending resolution of these issues, including replication in other cohorts, it will be difficult to formulate additional cost-effective pollution control strategies that are likely to benefit public health.

Air Pollutants↗
PubMed2006

Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk.

AIMS: To determine the relative frequency of mutations in three different genes (low-density lipoprotein receptor (LDLR), APOB, PCSK9), and to examine their effect in development of coronary heart disease (CHD) in patients with clinically defined definite familial hypercholesterolaemia in UK. PATIENTS AND METHODS: 409 patients with familial hypercholesterolaemia patients (158 with CHD) were studied. The LDLR was partially screened by single-strand conformational polymorphism (SSCP) (exons 3, 4, 6-10 and 14) and by using a commercial kit for gross deletions or rearrangements. APOB (p.R3500Q) and PCSK9 (p.D374Y) were detected by specific assays. Coding exons of PCSK9 were screened by SSCP. RESULTS: Mutations were detected in 253 (61.9%) PATIENTS: 236 (57.7%) carried LDLR, 10 (2.4%) carried APOB p.Q3500 and 7 (1.7%) PCSK9 p.Y374. No additional mutations were identified in PCSK9. After adjusting for age, sex, smoking and systolic blood pressure, compared to those with no detectable mutation, the odds ratio of having CHD in those with an LDLR mutation was 1.84 (95% CI 1.10 to 3.06), for APOB 3.40 (0.71 to 16.36), and for PCSK9 19.96 (1.88 to 211.5; p = 0.001 overall). The high risk in patients carrying LDLR and PCSK9 p.Y374 was partly explained by their higher pretreatment cholesterol levels (LDLR, PCSK9 and no mutation, 10.29 (1.85), 13.12 and 9.85 (1.90) mmol/l, respectively, p = 0.001). The post-statin treatment lipid profile in PCSK9 p.Y374 carriers was worse than in patients with no identified mutation (LDL-C, 6.77 (1.82) mmol/l v 4.19 (1.26) mmol/l, p = 0.001, HDL-C 1.09 (0.27) mmol/l v 1.36 (0.36) mmol/l, p = 0.03). CONCLUSIONS: The higher CHD risk in patients carrying PCSK9 p.Y347 or a detected LDLR mutation supports the usefulness of DNA testing in the diagnosis and management of patients with familial hypercholesterolaemia. Mutations in PCSK9 appear uncommon in patients with familial hypercholesterolaemia in UK.

Adult↗
PubMed2005

The AD8: a brief informant interview to detect dementia.

BACKGROUND: Brief measures that accurately discriminate normal cognitive aging from very mild dementia are lacking. Cognitive tests often are insensitive to very mild dementia. Informant-based measures may be more sensitive in detecting early dementia. OBJECTIVE: To identify informant-reported clinical variables that differentiate cognitively normal individuals from those with very mild dementia. METHODS: A 55-item battery of informant queries regarding an individual's cognitive status was derived from a semistructured interview and a consensus panel of dementia experts. The battery was evaluated with informants for 189 consecutive participants of a longitudinal study of memory and aging and compared with an independently obtained Clinical Dementia Rating (CDR) score for the participant. Multiple regression and receiver operator characteristic curves assessed subsets of the items to discriminate between CDR 0 (no dementia) and CDR 0.5 (very mild dementia). RESULTS: The final version (AD8) querying memory, orientation, judgment, and function was administered to an additional sample of 112 CDR 0 and 68 CDR 0.5 participants. Using a cut-off of two items endorsed, the area under the curve was 0.834, suggesting good to excellent discrimination, sensitivity was 74%, and specificity was 86% (prevalence of 0.38 for very mild dementia). Inclusion of 56 additional individuals with mild to severe dementia (increasing dementia prevalence to 0.53) increased sensitivity to 85%. CONCLUSIONS: The AD8 is a brief, sensitive measure that reliably differentiates between nondemented and demented individuals. Use of the AD8 in conjunction with a brief assessment of the participant could improve diagnostic accuracy in general practice.

Aged↗
PubMed2005

Preclinical detection of Alzheimer's disease: hippocampal shape and volume predict dementia onset in the elderly.

Structural deformity of the hippocampus is characteristic of individuals with very mild and mild forms of dementia of the Alzheimer type (DAT). The purpose of this study was to determine whether a similar deformity of the hippocampus can predict the onset of dementia in nondemented elders. Using high dimensional diffeomorphic transformations of a neuroanatomical template, hippocampal volumes and surfaces were defined in 49 nondemented elders; the hippocampal surface was subsequently partitioned into three zones (i.e., lateral, superior and inferior-medial), which were proximal to the underlying CA1 subfield, CA2-4 subfields plus dentate gyrus, and subiculum, respectively. Annual clinical assessments using the Clinical Dementia Rating scale (CDR), where CDR 0 indicates no dementia and CDR 0.5 indicates very mild dementia, were then performed for a mean of 4.9 years (range 0.9-7.1 years) to monitor subjects who converted from CDR 0 to CDR 0.5. Inward variation of the lateral zone and left hippocampal volume significantly predicted conversion to CDR 0.5 in separate Cox proportional hazards models. When hippocampal surface variation and volume were included in a single model, inward variation of the lateral zone of the left hippocampal surface was selected as the only significant predictor of conversion. The pattern of hippocampal surface deformation observed in nondemented subjects who later converted to CDR 0.5 was similar to the pattern of hippocampal surface deformation previously observed to discriminate subjects with very mild DAT and nondemented subjects. These results suggest that inward deformation of the left hippocampal surface in a zone corresponding to the CA1 subfield is an early predictor of the onset of DAT in nondemented elderly subjects.

Aged↗
PubMed2005

Alzheimer disease and cancer.

Cross-sectional studies raise the possibility of protective relationships between, or a common mechanism underlying, the development of dementia of the Alzheimer type (DAT) and cancer. Using a prospective longitudinal design, the authors found that the risk of developing cancer is less among participants with DAT vs nondemented participants (p < 0.001) and that the risk of developing DAT may be less for participants with a history of cancer (p = 0.060).

Age Factors↗
PubMed2005

Expression of Duffy antigen receptor for chemokines during reticulocyte maturation: using a CD71 flow cytometric technique to identify reticulocytes.

Flow cytometric methods commonly used to identify reticulocytes are of limited usefulness in malarious areas, since RNA staining also detects plasmodia. An important antigen expressed on reticulocytes is Duffy antigen receptor for chemokines (DARC, also known as Fy), the receptor for Plasmodium vivax. An early marker for reticulocytes is CD71 (transferrin receptor). We have been interested in CD71 as an alternative marker for reticulocytes in the context of Fy expression. Flow cytometry was used to determine the expression of Fy on CD71-positive and -negative reticulocytes and to correlate serology and genotype. A reduction of 13 percent was seen in Fy6 expression between CD71-positive reticulocytes and RNA-positive reticulocytes. CD71 disappears early during reticulocyte maturation, while Fy6 expression is relatively preserved. CD71 is an alternative to staining for RNA for reticulocyte assays relating to Fy6 expression.

Antigens, CD↗
PubMed2004

New method of measuring electric dipole moments in storage rings.

A new highly sensitive method of looking for electric dipole moments of charged particles in storage rings is described. The major systematic errors inherent in the method are addressed and ways to minimize them are suggested. It seems possible to measure the muon EDM to levels that test speculative theories beyond the standard model.

Journal Article↗
PubMed2004

Measurement of the negative muon anomalous magnetic moment to 0.7 ppm.

The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 ppm (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in 2001, and is over an order of magnitude more precise than the previous measurement for the negative muon. The result a(mu(-))=11 659 214(8)(3) x 10(-10) (0.7 ppm), where the first uncertainty is statistical and the second is systematic, is consistent with previous measurements of the anomaly for the positive and the negative muon. The average of the measurements of the muon anomaly is a(mu)(exp)=11 659 208(6) x 10(-10) (0.5 ppm).

Journal Article↗
PubMed2004

Established and emerging coronary risk factors in patients with heterozygous familial hypercholesterolaemia.

OBJECTIVES: To assess the clinical and biochemical factors associated with inter-individual variation in susceptibility to coronary artery disease (CAD) in treated heterozygous familial hypercholesterolaemia. DESIGN: A cross sectional study was conducted of 410 patients recruited from six lipid clinics in the UK. RESULTS: CAD was documented in 104 of the 211 men and in 55 of the 199 women with mean ages of onset of 43.1 and 46.5 years, respectively. CAD was significantly more common in men (49% v 28%, p < 0.001) and in patients who had smoked cigarettes versus patients who had never smoked (51% v 28%, p < 0.001). After adjusting for age, sex, and current smoking status, there were no significant differences between patients with or without CAD in lipoprotein(a), homocysteine, fibrinogen, plasminogen activator inhibitor-1, white blood cell count, body mass index, glucose, triglyceride or total cholesterol. However, high density lipoprotein (HDL) cholesterol concentrations were significantly lower in those with CAD (6%, 95% confidence interval (CI) 1% to 11%, p = 0.03) and this difference was greater in women than men (12% v 2%, p = 0.041). CONCLUSIONS: These results indicate that emerging coronary risk factors appear not to be associated with CAD in adults with treated familial hypercholesterolaemia, but the strong association with smoking suggests that patients should be identified early in childhood and discouraged from ever starting to smoke.

Adult↗
PubMed2003

The effect of movement velocity and movement pattern on the reciprocal co-activation of the hamstrings.

The effect of velocity and movement pattern (reciprocal vs. non-reciprocal) on the reciprocal co-activation of the hamstrings was investigated through analysis of the root mean square (RMS) and the median frequency (MDF) of surface electromyography (SEMG). Fourteen subjects performed six continuous repetitions of a reciprocal isokinetic movement pattern (maximal extension followed by maximal flexion), and six continuous repetitions of a non-reciprocal movement pattern (maximal extension only) at 100 degrees, 200 degrees, 300 degrees s-1, and 400 degrees s-1. Data were analyzed using separate 2 x 4 (movement pattern x angular velocity) repeated measures analysis of variance (ANOVA). No significant differences (p > 0.05) were noted between reciprocal and non-reciprocal movement patterns for RMS. However, results did reveal a velocity effect for RMS (F = 5.0, p < 0.01), with significant differences observed between 100 degrees s-1 and 400 degrees s-1 (F = 9.4, p < 0.01), 200 degrees s-1 and 400 degrees s-1 (F = 9.5, p < 0.01), and 300 degrees s-1 and 400 degrees s-1 (F = 11.0, p < 0.001), with RMS values at 400 degrees s-1 being the highest. There was also a velocity effect for MDF (F = 8.03, p < 0.001), with significant differences observed between 100 degrees s-1 and 300 degrees s-1 (F = 4.2, p < 0.05), 100 degrees s-1 and 400 degrees s-1 (F = 20.2, p < 0.0001), 200 degrees s-1 and 400 degrees s-1 (F = 15.221, p < 0.001), and 300 degrees s-1 and 400 degrees s-1 (F = 5.9, p < 0.01). In all cases the highest MDF values were exhibited at the lower velocities. Lastly, there was an interaction effect when comparing movement patterns at 400 degrees s-1, with MDF values being significantly higher during the non-reciprocal movement pattern than during the reciprocal movement pattern (F = 10.9, p < 0.01). Results indicated that during isokinetic movements, RMS and MDF activity of the hamstrings are altered as velocity changes. More specifically, as velocity increases overall hamstrings' co-activation increases and there is a shift in the power spectrum toward the recruitment of slower-twitch muscle fibers. Results also indicate that movement pattern (reciprocal vs. non reciprocal) does not effect appreciably SEMG activity of hamstrings' co-contraction.

Adult↗
PubMed2002

The clock drawing test is a poor screen for very mild dementia.

OBJECTIVE: To determine whether performance on the clock drawing test varies as a function of dementia severity and particularly whether it differentiates cognitively normal older adults from those with very mild dementia. METHODS: Clock drawings were obtained during the initial clinical assessments of 75 participants in a longitudinal study of healthy aging and dementia of the Alzheimer type (15 cognitively normal, 25 with very mild dementia, 21 with mild dementia, and 14 with moderate to severe dementia, as staged by the Clinical Dementia Rating). Each clock drawing later was judged blindly and independently by two raters according to six commonly used sets of scoring criteria. RESULTS: The same pattern of results was obtained for all six scoring methods. Inter-rater reliability was consistently high. Spearman correlations indicated that as dementia severity increased, clock drawing performance decreased. Analyses of variance revealed that although those with mild or moderate/severe dementia performed significantly worse on the clock drawing test than did individuals who had very mild dementia or who were cognitively normal, the latter two groups did not differ significantly. Sensitivity and specificity analyses revealed that all methods could distinguish between normal aging and dementia of at least mild severity. However, sensitivity for detecting very mild dementia was poor. CONCLUSION: Although the clock drawing test can be scored reliably and can differentiate cognitively normal older adults from those with at least mild dementia of the Alzheimer type, it does not appear to be a useful screening instrument for detecting very mild dementia.

Aged↗
PubMed2002

Measurement of the positive muon anomalous magnetic moment to 0.7 ppm.

A higher precision measurement of the anomalous g value, a(mu)=(g-2)/2, for the positive muon has been made at the Brookhaven Alternating Gradient Synchrotron, based on data collected in the year 2000. The result a(mu(+))=11 659 204(7)(5)x10(-10) (0.7 ppm) is in good agreement with previous measurements and has an error about one-half that of the combined previous data. The present world average experimental value is a(mu)(expt)=11 659 203(8)x10(-10) (0.7 ppm).

Journal Article↗
PubMed2001

Clinicopathologic assessment and grading of embolized meningiomas: a correlative study of 64 patients.

BACKGROUND: Preoperative embolization of meningiomas is commonly performed to minimize intraoperative bleeding, thereby facilitating surgery and reducing the necessity for transfusion. However, the resulting necrosis and compensatory proliferation reportedly have hampered subsequent histologic grading. METHODS: The clinicopathologic features of 64 meningiomas embolized between 1989 and 1997 were assessed. Tumors were graded according to recently published criteria. RESULTS: A good embolization result (> 75% reduction in angiographic blush) was achieved in 52%. Histologically, embolized meningiomas showed higher frequencies of necrosis (89%), nuclear atypia (72%), macronucleoli (58%), sheeting (31%), high mitotic index (30%), and brain invasion (14%) when compared with nonembolized counterparts. Median mitotic and MIB-1 indices were slightly elevated (1.5 of 10 high-power fields and 1.6%, respectively). A significant degree of necrosis (> 10%) was found in 43% and was only roughly correlated with extent of angiographic blush reduction or embolization particle size. Histologic grade was benign in 57.8%, atypical in 40.6%, and anaplastic in 1.6%. At last follow-up, there were 13 recurrences, 11 in the atypical/anaplastic (41%) versus 2 in the benign (5%) subsets (P = 0.001). CONCLUSIONS: The authors conclude that 1) their grading scheme accurately stratifies embolized meningiomas, 2) extent of necrosis is difficult to predict using standard clinical parameters, and 3) their high incidence of atypical meningioma more likely reflects patient selection biases rather than artifacts induced by the embolization procedure.

Adult↗
PubMed2001

Precise measurement of the positive muon anomalous magnetic moment.

A precise measurement of the anomalous g value, a(mu) = (g-2)/2, for the positive muon has been made at the Brookhaven Alternating Gradient Synchrotron. The result a(mu+) = 11 659 202(14) (6) x 10(-10) (1.3 ppm) is in good agreement with previous measurements and has an error one third that of the combined previous data. The current theoretical value from the standard model is a(mu)(SM) = 11 659 159.6(6.7) x 10(-10) (0.57 ppm) and a(mu)(exp) - a(mu)(SM) = 43(16) x 10(-10) in which a(mu)(exp) is the world average experimental value.

Journal Article↗
PubMed2001

Mild cognitive impairment represents early-stage Alzheimer disease.

BACKGROUND: Mild cognitive impairment (MCI) is considered to be a transitional stage between aging and Alzheimer disease (AD). OBJECTIVE: To determine whether MCI represents early-stage AD by examining its natural history and neuropathologic basis. DESIGN: A prospective clinical and psychometric study of community-living elderly volunteers, both nondemented and minimally cognitively impaired, followed up for up to 9.5 years. Neuropathologic examinations were performed on participants who had undergone autopsy. SETTING: An AD research center. PARTICIPANTS: All participants enrolled between July 1990 and June 1997 with Clinical Dementia Rating (CDR) scores of 0 (cognitively healthy; n = 177; mean age, 78.9 years) or 0.5 (equivalent to MCI; n = 277; mean age, 76.9 years). Based on the degree of clinical confidence that MCI represented dementia of the Alzheimer type (DAT), 3 subgroups of individuals with CDR scores of 0.5 were identified: CDR 0.5/DAT, CDR 0.5/incipient DAT, and CDR 0.5/uncertain dementia. MAIN OUTCOME MEASURE: Progression to the stage of CDR 1, which characterizes mild definite DAT. RESULTS: Survival analysis showed that 100% of CDR 0.5/DAT participants progressed to greater dementia severity over a 9.5-year period. At 5 years, rates of progression to a score of CDR 1 (or greater) for DAT were 60.5% (95% confidence interval [CI], 50.2%-70.8%) for the CDR 0.5/DAT group, 35.7% (95% CI, 21.0%-50.3%) for the CDR 0.5/incipient DAT group, 19.9% (95% CI, 8.0%-31.8%) for the CDR 0.5/uncertain dementia group, and 6.8% (95% CI, 2.2%-11.3%) for CDR 0/controls. Progression to greater dementia severity correlated with degree of cognitive impairment at baseline. Twenty-four of the 25 participants with scores of CDR 0.5 had a neuropathologic dementing disorder, which was AD in 21 (84%). CONCLUSIONS: Individuals currently characterized as having MCI progress steadily to greater stages of dementia severity at rates dependent on the level of cognitive impairment at entry and they almost always have the neuropathologic features of AD. We conclude that MCI generally represents early-stage AD.

Aged↗
PubMed2001

Accuracy of predonation Hct sampling affects donor safety, eligibility, and deferral rates.

BACKGROUND: Safe blood donation depends upon reliable predonation Hct screening. Earstick (ES) capillary samples are frequently used, but they may not be accurate. STUDY DESIGN AND METHODS: Predonation ES and fingerstick (FS) and postdonation venous Hct results were compared in 1960 whole-blood and 210 apheresis donors. The validity of using postdonation venous samples to evaluate predonation ES and FS Hct was assessed in 20 whole-blood donors. The impact of Hct screening method on donor Hct deferrals was examined during periods when either ES or FS sampling was used exclusively. RESULTS: All donors were eligible to donate on the basis of a predonation capillary Hct of > or = 38 percent. In venous samples obtained immediately after donation, 36 percent of whole-blood donors had a Hct <38 percent. With correction for a decrease of approximately 2 Hct units during donation, 20 percent of these donors had a predonation Hct <38 percent. The lowest venous Hct was 23.1 percent. FS samples showed better correlation with venous Hct. Hct discrepancies were similar for apheresis donors. Hct deferrals were significantly higher with FS sampling, especially among women. CONCLUSION: Hct determinations from ES samples overestimate venous Hct. Fingerstick samples are more sensitive in detecting anemia. The accuracy of predonation Hct sampling has implications for donor safety, eligibility, and deferral rates.

Blood Component Removal↗
PubMed2001

Methicillin-resistant Staphylococcus aureus sepsis associated with the transfusion of contaminated platelets: a case report.

BACKGROUND: Platelet transfusion-associated sepsis is usually due to donor skin flora introduced into the unit during phlebotomy. An unusual case of a platelet component contaminated with methicillin-resistant Staphylococcus aureus (MRSA) is reported. CASE REPORT: A 54-year-old man, terminally ill with progressive non-Hodgkin's lymphoma, developed fever and hypotension during a platelet transfusion. He was receiving multiple antibiotics, including vancomycin. Blood cultures taken soon after transfusion were negative. An aliquot taken from the platelet pool grew MRSA at a count of 1.6 x 10(8) CFUs per mL. One of the individual bags constituting the pool showed MRSA at a count of 5.1 x 10(8) CFUs per mL. The patient died soon after the platelet transfusion. This case was reported to the FDA and submitted to the BaCon Study. The identity of the isolate and its methicillin resistance were confirmed by the CDC as part of the BaCon Study protocol. The source of contamination of the implicated unit could not be established with certainty. CONCLUSION: The emergence of antimicrobial-resistant organisms poses additional challenges for the diagnosis and treatment of transfusion-associated sepsis. Measures to prevent or intercept the transfusion of contaminated platelets should be developed.

Blood Platelets↗