Search tips
Search criteria

Results 1-11 (11)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  Validation of a serum screen for Alzheimer’s disease across assay platforms, species and tissues 
Journal of Alzheimer's disease : JAD  2014;42(4):1325-1335.
There is a significant need for rapid and cost-effective biomarkers of Alzheimer’s disease (AD) for advancement of clinical practice and therapeutic trials.
The aim of the current study was to cross-validate our previously published serum-based algorithm on an independent assay platform as well as validate across tissues and species. Preliminary analyses were conducted to examine the utility in distinguishing AD from non-AD neurological disease (Parkinson’s Disease).
Serum proteins from our previously published algorithm were quantified from 150 AD cases and 150 controls on the Meso Scale Discovery (MSD) platform. Serum samples were analyzed from 49 Parkinson’s disease (PD) cases and compared to a random sample of 51 AD cases and 62 controls. Support vector machines (SVM) were used to discriminate PD vs. AD vs. NC. Human and AD mouse model microvessel images were quantified with HAMAMATSU imaging software. Mouse serum biomarkers were assayed via MSD.
Analysis of 21 serum proteins from 150 AD cases and 150 controls yielded an algorithm with sensitivity and specificity of 0.90 for correctly classifying AD. This multi-marker approach was then validated across species and tissue. Assay of the top proteins in human and AD mouse model brain microvessels correctly classified 90–100% of the samples. SVM analyses were highly accurate at distinguishing PD vs. AD vs. NC.
This serum-based biomarker panel should be tested in a community-based setting to determine its utility as a first-line screen for AD and non-AD neurological diseases for primary care providers.
PMCID: PMC4400808  PMID: 25024345
Alzheimer’s Disease; blood-based biomarkers; tissue; species; serum
2.  Impact of Ethnicity in Upper Gastrointestinal Hemorrhage 
To examine ethnicity's role in the etiology and outcome of upper gastrointestinal hemorrhage (UGIH).
UGIH is a serious condition with considerable associated morbidity and mortality.
We analyzed 2196 patients admitted with acute UGIH between January 2006 and February 2012. Complete clinical data was gathered prospectively and entered into our GI Bleed Registry, which captures demographic and clinical variables. Results were analyzed using the Chi-square analyses and the analysis of variance techniques with Tukey multiple comparisons.
Among 2196 patients, 620 (28%) were Black, 625 (29%) White, 881 (40%) Hispanic, and 70 (3%) were members of other ethnicities. Gastroduodenal ulcers (25%), esophageal varices (25%), and esophagitis (12%) were the most frequently identified causes of UGIH. Blacks experienced a high rate of gastroduodenal ulcers (199/620), while Hispanics most commonly had esophageal varices. In all ethnicities, the most common cause of bleeding in patients younger than 35 or older than 65 was gastroduodenal ulcer disease. However, among patients aged 35-64, there were differences in the etiology of UGIH. Blacks aged 50-64 frequently experienced gastroduodenal ulcers, while Hispanics aged 35-49 typically had esophageal varices. Rebleeding rates were significantly lower in Whites (5.8%) than in Hispanics (9.9%) or Blacks (8.7%) (p=0.02).
By examining a diverse population, we conclude that UGIH may follow trends. Hispanics were likely to have esophageal varices and higher rebleeding rates, while Blacks were likely to have ulcers and the highest mortality. Whites were equally likely to have ulcers or varices, but a lower rate of rebleeding.
PMCID: PMC4157370  PMID: 24275716
bleeding; varices; peptic ulcer; demographics; mortality
3.  Risk factors for mild cognitive impairment among Mexican Americans 
While a great deal of literature has focused on risk factors for Mild Cognitive Impairment (MCI), little published work examines risk for MCI among Mexican Americans.
Data from 1628 participants (non-Hispanic n= 1002; Mexican American n=626) were analyzed from two ongoing studies of cognitive aging and Alzheimer’s disease, Project FRONTIER and TARCC.
When looking at the full cohorts (non-Hispanic and Mexican American), age, education, APOE ε4 status and gender were consistently related to MCI diagnosis across the two cohorts. However, when split by ethnicity advancing age was the only significant risk factor for MCI among Mexican Americans across both cohorts.
The current data suggests that many of the previously established risk factors for MCI among non-Hispanic cohorts may not be predictive of MCI among Mexican Americans and point to the need for additional work aimed at understanding factors related to cognitive aging among this underserved segment of the population.
PMCID: PMC3737282  PMID: 23643456
Mexican American; Mild Cognitive Impairment; cognition; Alzheimer’s disease; ethnicity; cross-cultural; risk factors
4.  Androgen receptor gene and gender specific Alzheimer’s disease 
Neurobiology of aging  2013;34(8):2077.e19-2077.e20.
Women are at a twofold risk of developing late onset Alzheimer’s disease (LOAD) (onset ≥65 years of age) compared to men. During perimenopausal years, women undergo hormonal changes that are accompanied by metabolic, cardiovascular and inflammatory changes. These all together have been suggested as risk factors for LOAD. However, not all perimenopausal women develop AD; we hypothesize that certain genetic factors might underlie the increased susceptibility for developing AD in postmenopausal women. We investigated the androgen receptor (AR) gene in a clinical cohort of male and female AD patients and normal controls by sequencing all coding exons and evaluating the length and distribution of the CAG repeat in exon 1. We could not establish a correlation between the repeat length, gender and the disease status, nor did we identify possible pathogenic variants. AR is located on the X chromosome; in order to assess its role in AD, X-inactivation patterns will need to be studied to directly correlate the actual expressed repeat length to a possible sex specific phenotypic effect.
PMCID: PMC4012749  PMID: 23545426
Alzheimer’s disease; androgen receptor; menopause; X-inactivation; epigenetics
5.  Acetaminophen Dose Does Not Predict Outcome in Acetaminophen-Induced Acute Liver Failure 
Acetaminophen is a dose-dependent toxin. Prognosis in severe acute liver injury is related presumably in part to the dose ingested. We sought to assess the value of acetaminophen dosing information in patients with acute liver failure (ALF) due to acetaminophen toxicity to determine the role of dose as a prognostic indicator.
Prospective data from 113 patients with ALF having single-time-point ingestions of acetaminophen were analyzed. Multivariate and χ2 tests were used to determine the relationship of dose to clinical outcome. We also used the Mann-Whitney U test to compare prognosis and survival in ALF with acetaminophen dose ingested.
Multivariate and χ2 analyses failed to show any relationship between acetaminophen dose and spontaneous survival. A separate analysis showed no correlation between acetaminophen dose and clinical prognostic indicators.
Dose of acetaminophen ingested did not seem to play a role in prognosis. The most important prognostic factor was coma grade on admission to study. Acetaminophen dosing information is not always obtainable. When it is, it adds little to the clinical assessment. Severity of encephalopathy is a more reliable indicator of prognosis in these critically ill patients.
PMCID: PMC3618971  PMID: 20305573
acetaminophen; acute liver failure; N-acetylcysteine
6.  Effect of Spironolactone on Patients With Atrial Fibrillation and Structural Heart Disease 
Clinical cardiology  2011;34(7):415-419.
Several studies have shown that the modulation of fibrotic scar in cardiac diseases has beneficial effects on cardiac arrhythmias. In addition, recent reports suggest a potential role of mineralocorticoid receptor upregulation in atrial fibrillation (AF). The role of spironolactone, a mineralocorticoid receptor blocker and a potent antifibrotic agent, in AF is as yet unexplored. The aim of this study was to determine if spironolactone, a mineralocorticoid receptor blocker with potent antifibrotic properties, has beneficial effects on AF.
Spironolactone therapy in patients with atrial fibrillation provides additional clinical benefits in addition to the current conventional pharmacological agents.
A comprehensive retrospective analysis was performed on 83 patients with AF, including 23 who were treated with spironolactone for ≥ 3 months. The combined primary outcome of hospitalization for AF or direct current cardioversion (DCCV) was compared between patients treated with spironolactone in addition to the usual care for AF and those receiving conventional medical therapy alone.
Patients receiving spironolactone had significantly fewer primary outcome events (AF-related hospitalizations or DCCV) (22% vs 53%, P = 0.027).
Spironolactone therapy is associated with a reduction in the burden of AF, as reflected by a combination of hospitalizations for AF and DCCV. Larger randomized controlled studies should be performed to evaluate the efficacy and safety of spironolactone as an adjunctive therapy for patients with AF.
PMCID: PMC3617486  PMID: 21674535
7.  A Blood-Based Algorithm for the Detection of Alzheimer's Disease 
We previously created a serum-based algorithm that yielded excellent diagnostic accuracy in Alzheimer's disease. The current project was designed to refine that algorithm by reducing the number of serum proteins and by including clinical labs. The link between the biomarker risk score and neuropsychological performance was also examined.
Serum-protein multiplex biomarker data from 197 patients diagnosed with Alzheimer's disease and 203 cognitively normal controls from the Texas Alzheimer's Research Consortium were analyzed. The 30 markers identified as the most important from our initial analyses and clinical labs were utilized to create the algorithm.
The 30-protein risk score yielded a sensitivity, specificity, and AUC of 0.88, 0.82, and 0.91, respectively. When combined with demographic data and clinical labs, the algorithm yielded a sensitivity, specificity, and AUC of 0.89, 0.85, and 0.94, respectively. In linear regression models, the biomarker risk score was most strongly related to neuropsychological tests of language and memory.
Our previously published diagnostic algorithm can be restricted to only 30 serum proteins and still retain excellent diagnostic accuracy. Additionally, the revised biomarker risk score is significantly related to neuropsychological test performance.
PMCID: PMC3169374  PMID: 21865746
Algorithm, blood-based; Alzheimer's disease; Diagnosis
8.  Staging Dementia Using Clinical Dementia Rating Scale Sum of Boxes Scores 
Archives of neurology  2008;65(8):1091-1095.
The Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score is commonly used, although the utility regarding this score in staging dementia severity is not well established.
To investigate the effectiveness of CDRSOB scores in staging dementia severity compared with the global CDR score.
Retrospective study.
Texas Alzheimer's Research Consortium minimum data set cohort.
A total of 1577 participants (110 controls, 202 patients with mild cognitive impairment, and 1265 patients with probable Alzheimer disease) were available for analysis.
Main Outcome Measures
Receiver operating characteristic curves were generated from a derivation sample to determine optimal cutoff scores and ranges, which were then applied to the validation sample.
Optimal ranges of CDR-SOB scores corresponding to the global CDR scores were 0.5 to 4.0 for a global score of 0.5, 4.5 to 9.0 for a global score of 1.O, 9.5 to 15.5 for a global score of 2.0, and 16.0 to 18.0 for a global score of 3.0. When applied to the validation sample, κ scores ranged from 0.86 to 0.94 (P <.001 for all), with 93.0% of the participants falling within the new staging categories.
The CDR-SOB score compares well with the global CDR score for dementia staging. Owing to the increased range of values, the CDR-SOB score offers several advantages over the global score, including increased utility in tracking changes within and between stages of dementia severity. Interpretive guidelines for CDR-SOB scores are provided.
PMCID: PMC3409562  PMID: 18695059
9.  Elevated Serum Pesticide Levels and Risk of Parkinson Disease 
Archives of Neurology  2009;66(7):870-875.
Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains.
To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD.
Case-control study.
An academic medical center.
Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease.
Main Outcome Measures
Levels of 16 organochlorine pesticides in serum samples.
β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD.
These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD.
PMCID: PMC3383784  PMID: 19597089
10.  A Serum Protein-Based Algorithm for the Detection of Alzheimer's Disease 
Archives of neurology  2010;67(9):1077-1081.
Alzheimer's disease (AD) is the most common form of age-related dementia and one of the most serious health problems in the industrialized world. Biomarker approaches to diagnostics would be more time and cost effective and may also be useful for identifying endophenotypes within AD patient populations.
We analyzed serum protein-based multiplex biomarker data from 197 patients diagnosed with AD and 203 controls from a longitudinal study of Alzheimer's disease being conducted by the Texas Alzheimer's Research Consortium to develop an algorithm that separates AD from controls. The total sample was randomized equally into training and test sets and random forest methods were applied to the training set to create a biomarker risk score.
The biomarker risk score had a sensitivity and specificity of 0.80 and 0.91, respectively and an AUC of 0.91 in detecting AD. When age, gender, education, and APOE status were added to the algorithm, the sensitivity, specificity, and AUC were 0.94, 0.84, and 0.95, respectively.
These initial data suggest that serum protein-based biomarkers can be combined with clinical information to accurately classify AD. Of note, a disproportionate number of inflammatory and vascular markers were weighted most heavily in analyses. Additionally, these markers consistently distinguished cases from controls in SAM, logistic regression and Wilcoxon analyses, suggesting the existence of an inflammatory-related endophenotype of AD that may provide targeted therapeutic opportunities for this subset of patients.
PMCID: PMC3069805  PMID: 20837851
11.  UTHSCD-ISP: Interactive Statistical Programs in a Medical Environment 
Interactive statistical programs have been developed at The University of Texas Health Science Center at Dallas (UTHSCD) to handle the common as well as special statistical data analysis needs in medical research. UTHSCD-ISP is user-friendly; it can be accessed from a CRT terminal with a minimum of prior instruction. The user can step through the program by answering questions with a one word response (“yes,” “no,” etc.) or with a code number to designate a specific response. Data are entered interactively or called from an existing file. Information regarding the appropriate statistical analysis choice is given when alternative analyses are provided. Significance levels or references to tables are given and references for further reading are listed. Graphical output is included with several of the programs and the results can be obtained in printed form at the option of the user. Currently, the UTHSCD-ISP programs are available on the DEC-10 and DEC-20 computers.
PMCID: PMC2580329

Results 1-11 (11)