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Biomedical subjects

Linda S Hynan

Publications and source records attributed to Linda S Hynan.

At least 19 recordsLinked to original sources
PubMed2006

MMSE scores decline at a greater rate in frontotemporal degeneration than in AD.

The clinical diagnostic criteria for frontotemporal degeneration (FTD) include relative preservation of memory and visuospatial function, in contradistinction to characteristics of Alzheimer's disease (AD). The Mini-Mental State Examination (MMSE) contains items to assess these areas of cognition. In a retrospective case-control study of participants at two institutionally-based AD centers, we determined whether total MMSE and MMSE subscores would reflect the disease progression projected by the clinical criteria of FTD vs. AD. Participants were 44 subjects with FTD (7 pathologically confirmed) and 45 with pathologically confirmed AD. Each subject had at least two MMSEs with minimum inter-test intervals of 9 months. We compared annualized rates of change for total MMSE scores and cognitive domain subscores over time and between groups by two independent samples t-tests and proportion tests. The total MMSE score (p = 0.03) and language subscore (p = 0.02) showed a greater rate of decline for the FTD group than the AD group, although the constructional praxis item declined less rapidly in the FTD group (p = 0.018). Changes in MMSE subscores paralleled the clinical diagnostic criteria for FTD. The more rapid progression on the language subscore was observed in both language and behavioral variants of FTD.

Aged↗
PubMed2006

Comparison of the test of everyday functional abilities with a direct measure of daily function.

OBJECTIVES: To compare scores for dementia patients on a newly developed direct test of instrumental activities of daily living (IADLs) to scores on a widely accepted functional measure. METHODS: In 27 community-dwelling dementia patients, scores for the Test of Everyday Functional Ability (TEFA) were compared with scores on a widely used direct test of daily function (Independent Living Scale; ILS). RESULTS: Mini-Mental State Examination scores ranged from 5 to 28 (mean +/- SD = 20.7 +/- 6.37). There was a highly significant correlation between total TEFA and total ILS scores (r(25) = 0.892, p < 0.001) as well as many of the comparable subscales. CONCLUSION: The TEFA is a valid measure of IADL competence for dementia patients.

Activities of Daily Living↗
PubMed2006

The gross motor function measure is a valid and sensitive outcome measure for spinal muscular atrophy.

Spinal muscular atrophy is a genetic disease of the anterior horn cell with high morbidity rate in childhood. Certain drugs may be of benefit and are in or under consideration for Phase II trials. Outcome measures that are age appropriate and representative of disease activity remain under study. Several have not yet been validated for spinal muscular atrophy. The Gross Motor Function Measure is a measure of motor function. We showed previously that the Gross Motor Function Measure is a reliable outcome measure to assess motor function in children with spinal muscular atrophy. By collating our data from 40 spinal muscular atrophy patients, ages 5 through 17 years, we now show the validity of the Gross Motor Function Measure when compared to Quantitative Muscle Testing and ambulatory status in children with spinal muscular atrophy. The median for Gross Motor Function Measure total scores for walkers was 237 (range: 197-261) and for non-walkers, 64 (range: 4-177; P<0.0001) with no distributional overlap. We conclude that the Gross Motor Function Measure is valid and sensitive as an outcome measure for clinical trials in pediatric spinal muscular atrophy.

Adolescent↗
PubMed2006

Abeta42 gene vaccination reduces brain amyloid plaque burden in transgenic mice.

OBJECTIVE: To demonstrate that in APPswe/PS1DeltaE9 transgenic mice, gene gun mediated Abeta42 gene vaccination elicits a high titer of anti-Abeta42 antibodies causal of a significant reduction of Abeta42 deposition in brain. METHODS: Gene gun immunization is conducted with transgenic mice using the Abeta42 gene in a bacterial plasmid with the pSP72-E3L-Abeta42 construct. Enzyme-linked immunoabsorbent assays (ELISA) and Western blots are used to monitor anti-Abeta42 antibody levels in serum and Abeta42 levels in brain tissues. Enzyme-linked immunospot (ELISPOT) assays are used for detection of peripheral blood T cells to release gamma-interferon. Immunofluorescence detection of Abeta42 plaques and quantification of amyloid burden of brain tissue were measured and sections were analyzed with Image J (NIH) software. RESULTS: Gene gun vaccination with the Abeta42 gene resulted in high titers of anti-Abeta42 antibody production of the Th2-type. Levels of Abeta42 in treated transgenic mouse brain were reduced by 60-77.5%. The Mann-Whitney U-test P=0.0286. INTERPRETATION: We have developed a gene gun mediated Abeta42 gene vaccination method that is efficient to break host Abeta42 tolerance without using adjuvant and induces a Th2 immune response. Abeta42 gene vaccination significantly reduces the Abeta42 burden of the brain in treated APPswe/PS1DeltaE9 transgenic mice with no overlap between treated and control mice.

Alzheimer Disease↗
PubMed2006

Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group.

OBJECTIVES: To determine short-term outcome for children with acute liver failure (ALF) as it relates to cause, clinical status, and patient demographics and to determine prognostic factors. STUDY DESIGN: A prospective, multicenter case study collecting demographic, clinical, laboratory, and short-term outcome data on children from birth to 18 years with ALF. Patients without encephalopathy were included if the prothrombin time and international normalized ratio remained > or = 20 seconds and/or >2, respectively, despite vitamin K. Primary outcome measures 3 weeks after study entry were death, death after transplantation, alive with native liver, and alive with transplanted organ. RESULTS: The cause of ALF in 348 children included acute acetaminophen toxicity (14%), metabolic disease (10%), autoimmune liver disease (6%), non-acetaminophen drug-related hepatotoxicity (5%), infections (6%), other diagnosed conditions (10%); 49% were indeterminate. Outcome varied between patient sub-groups; 20% with non-acetaminophen ALF died or underwent liver transplantation and never had clinical encephalopathy. CONCLUSIONS: Causes of ALF in children differ from in adults. Clinical encephalopathy may not be present in children. The high percentage of indeterminate cases provides an opportunity for investigation.

Adolescent↗
PubMed2006

Tc-99m HMPAO SPECT in the differential diagnosis of the dementias with histopathologic confirmation.

PURPOSE: The purpose of this study is to determine the value of Tc-99m HMPAO SPECT in the diagnosis of the dementias, with particular reference to Alzheimer disease. MATERIALS AND METHODS: Tc-99m HMPAO was used with a 3-camera scanner to produce 5 sets of sectional images of the brain. Diagnosis was made by a physician blinded to the clinical diagnosis. Results in 49 subjects were ultimately compared with neuropathologic study of the brain at autopsy. RESULTS: Sensitivity = 86.7% (68.4-95.6%, 95% confidence interval [CI]), specificity = 89.5% (65.5-98.2% CI), positive predictive value = 92.9% (75.0-98.8% CI), negative predictive value = 81% (57.4-93.7% CI), accuracy = 87.8% (74.5-94.9% CI), likelihood ratio = 8.23% (7.09-9.57% CI). CONCLUSIONS: Comparison is made with several other SPECT and PET series with histopathologic correlation. Brain blood flow SPECT is useful in the diagnosis and differential diagnosis of the dementias.

Aged↗
PubMed2006

Vascular disease and risk factors, rate of progression, and survival in Alzheimer's disease.

Two hundred forty-seven patients with early Alzheimer's disease were studied for the association of demographic, functional, and cognitive status and vascular comorbidities and risk factors present at index visit to rate of clinical disease progression over 3 years and to survival time. Patients who progressed to the moderate stage were designated fast progressors; those who remained in the early stage were designated slow progressors. At index visit, Mini-Mental State Exam score was significantly lower for the fast than the slow group; global impairment was significantly higher for the fast group. Cognitive scores showed greater annual decline in the fast group, and the fast group also had a greater annualized global change. The fast group had a shorter median survival time from onset, but age at onset, age at initial visit, history of heart problems, myocardial infarct, stroke, hypertension, diabetes, or past or current smoking did not differ between groups.

Aged↗
PubMed2006

Feasibility of telecognitive assessment in dementia.

Videoconferencing (VC) technology has been used successfully to provide psychiatric services to patients in rural and otherwise underserved settings. VC-based diagnostic interviewing has shown good agreement with conventional face-to-face diagnosis of dementia in several investigations, but extension of this technology to neurocognitive assessment has received little attention. To this end, the authors administered a brief battery of common neuropsychological tests via VC technology (telecognitive) and traditional face-to-face methods to 14 older persons with mild cognitive impairment (MCI) and 19 persons with mild to moderate Alzheimer's disease (AD). Highly similar test scores were obtained when participants were tested in-person or via VC. Telecognitive assessment appears to be a valid means to conduct neuropsychological evaluation of older adults with cognitive impairment. Furthermore, continued development of VC technology has implications for expanding neuropsychological assessment options in under-served populations.

Aged↗
PubMed2006

Detection of acetaminophen protein adducts in children with acute liver failure of indeterminate cause.

OBJECTIVE: Acetaminophen cysteine protein adducts are a widely recognized correlate of acetaminophen-mediated hepatic injury in laboratory animals. The objective of this study was to use a new assay for the detection of acetaminophen cysteine protein adducts in children with acute liver failure to determine the role of acetaminophen toxicity in acute liver failure of unknown cause. METHODS: Serum samples from children with acute liver failure were measured for acetaminophen cysteine protein adducts using high-performance liquid chromatography with electrochemical detection. For comparison, samples from children with well-characterized acetaminophen toxicity and children with known other causes of acute liver failure also were measured for acetaminophen cysteine protein adducts. The analytical laboratory was blinded to patient diagnoses. RESULTS: Acetaminophen cysteine protein adduct was detected in 90% of samples from children with acute liver failure that was attributed to acetaminophen toxicity, 12.5% of samples from children with acute liver failure of indeterminate cause, and 9.6% of samples from children with acute liver failure that was attributed to other causes. Adduct-positive patients from the indeterminate cause subgroup had higher levels of serum aspartate aminotransferase and alanine aminotransferase and lower levels of bilirubin. Adduct-positive patients also had lower rates of transplantation and higher rates of spontaneous remission. CONCLUSIONS: A small but significant percentage of children with acute liver failure of indeterminate cause tested positive for acetaminophen cysteine protein adducts, strongly suggesting acetaminophen toxicity as the cause of acute liver failure. An assay for the detection of acetaminophen cysteine protein adducts can aid the diagnosis of acetaminophen-related liver injury in children.

Acetaminophen↗
PubMed2006

Preparing data for analysis using microsoft Excel.

A critical component essential to good research is the accurate and efficient collection and preparation of data for analysis. Most medical researchers have little or no training in data management, often causing not only excessive time spent cleaning data but also a risk that the data set contains collection or recording errors. The implementation of simple guidelines based on techniques used by professional data management teams will save researchers time and money and result in a data set better suited to answer research questions. Because Microsoft Excel is often used by researchers to collect data, specific techniques that can be implemented in Excel are presented.

Biomedical Research↗
PubMed2005

Platelet amyloid precursor protein processing: a bio-marker for Alzheimer's disease.

The amyloid precursor protein (APP) in brain is processed either by an amyloidogenic pathway by beta-secretase and gamma-secretase to yield Abeta (beta-amyloid 4 kDa) peptide or by alpha-secretase within the beta-amyloid domain to yield non-amyloidogenic products. We have studied blood platelet levels of a 22-kDa fragment containing the Abeta (beta-amyloid 4 kDa) peptide, beta-secretase (BACE1), alpha-secretase (ADAM10), and APP isoform ratios of the 120-130 kDa to 110 kDa peptides from 31 Alzheimer's disease (AD) patients and 10 age-matched healthy control subjects. We found increased levels of Abeta4, increased activation of beta-secretase (BACE1), decreased activation of alpha-secretase (ADAM10) and decreased APP ratios in AD patients compared to normal control subjects. These observations indicate that the blood platelet APP is processed by the same amyloidogenic and non-amyloidogenic pathways as utilized in brain and that APP processing in AD patients is altered compared to control subjects and may be a useful bio-marker for the diagnosis of AD, the progression of disease and for monitoring drug responses in clinical trials.

ADAM Proteins↗
PubMed2005

Abnormal concentrations of esterified carnitine in bile: a feature of pediatric acute liver failure with poor prognosis.

The etiology of acute liver failure in children is unknown in a large number of cases. Defects in fatty acid oxidation have been shown to lead to severe liver injury. This retrospective analysis examined the bile acylcarnitine profiles of 27 children with acute liver failure who underwent liver transplantation or died. Results were compared with 758 postmortem samples from individuals without acute liver failure. Cumulative amounts of free carnitine, medium- or long-chain species in excess of the 95th percentile of the control group were considered abnormal. Fourteen samples had normal profiles. Three had markedly elevated concentrations of free carnitine, whereas ten showed elevations in medium- or long-chain species. The relative risk of death was 2.86 (95% confidence interval, 1.08-7.54, P = .01) in the 10 children with elevated concentrations of medium- or long-chain species compared with those with normal analyses. Overall, medium- and long-chain acylcarnitines were increased in those patients who died compared with survivors, (dead vs. alive; medium-chain, 187 +/- 74 vs. 32 +/- 12 micromol/L, P = .008; long-chain, 146 +/- 74 vs. 15 +/- 8 micromol/L, mean +/- standard error of the mean, P = .018). These studies describe biliary free and esterified carnitine profiles in children with acute liver failure. In conclusion, the findings raise the hypothesis that abnormalities in fatty acid oxidation may predispose to a worse outcome in acute liver failure.

Bile↗
PubMed2005

Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study.

Severe acetaminophen hepatotoxicity frequently leads to acute liver failure (ALF). We determined the incidence, risk factors, and outcomes of acetaminophen-induced ALF at 22 tertiary care centers in the United States. Detailed prospective data were gathered on 662 consecutive patients over a 6-year period fulfilling standard criteria for ALF (coagulopathy and encephalopathy), from which 275 (42%) were determined to result from acetaminophen liver injury. The annual percentage of acetaminophen-related ALF rose during the study from 28% in 1998 to 51% in 2003. Median dose ingested was 24 g (equivalent to 48 extra-strength tablets). Unintentional overdoses accounted for 131 (48%) cases, intentional (suicide attempts) 122 (44%), and 22 (8%) were of unknown intent. In the unintentional group, 38% took two or more acetaminophen preparations simultaneously, and 63% used narcotic-containing compounds. Eighty-one percent of unintentional patients reported taking acetaminophen and/or other analgesics for acute or chronic pain syndromes. Overall, 178 subjects (65%) survived, 74 (27%) died without transplantation, and 23 subjects (8%) underwent liver transplantation; 71% were alive at 3 weeks. Transplant-free survival rate and rate of liver transplantation were similar between intentional and unintentional groups. In conclusion, acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States. Susceptible patients have concomitant depression, chronic pain, alcohol or narcotic use, and/or take several preparations simultaneously. Education of patients, physicians, and pharmacies to limit high-risk use settings is recommended.

APACHE↗
PubMed2005

An ecological study of the association of environmental chemicals on breast cancer incidence in Texas.

PURPOSE: To investigate the role of environment in breast cancer development, we conducted an ecological study to examine the association of releases for selected industrial chemicals with breast cancer incidence in Texas. METHODS: During 1995--2000, 54,487 invasive breast cancer cases were reported in Texas. We identified 12 toxicants released into the environment by industry that: (1) were positively associated with breast cancer in epidemiological studies, (2) were Environmental Protection Agency (EPA) Toxics Release Inventory (TRI) chemicals designated as carcinogens or had estrogenic effects associated with breast cancer risk, and (3) had releases consistently reported to EPA TRI for multiple Texas counties during 1988--2000. We performed univariate, and multivariate analyses adjusted for race and ethnicity to examine the association of releases for these toxicants during 1988--2000 with the average annual age-adjusted breast cancer rate at the county level. RESULTS: Univariate analysis indicated that formaldehyde, methylene chloride, styrene, tetrachloroethylene, trichloroethylene, chromium, cobalt, copper, and nickel were positively associated with the breast cancer rate. Multivariate analyses indicated that styrene was positively associated with the breast cancer rate in women and men (beta=0.219, p=.004), women (beta=0.191, p=0.002), and women >or= 50 years old (beta=0.187, p=0.002). CONCLUSION: Styrene was the most important environmental toxicant positively associated with invasive breast cancer incidence in Texas, likely involving women and men of all ages. Styrene may be an important breast carcinogen due to its widespread use for food storage and preparation, and its release from building materials, tobacco smoke, and industry.

Adolescent↗
PubMed2005

Induction therapy with basiliximab allows delayed initiation of cyclosporine and preserves renal function after cardiac transplantation.

BACKGROUND: Cyclosporine (CsA) is frequently initiated as induction therapy in patients undergoing orthotopic heart transplantation, but our experience has identified a significant rate of post-operative renal dysfunction. We therefore devised a renal-sparing cyclosporine-free induction regimen consisting of the early administration basiliximab, an interleukin-2 receptor monoclonal antibody, followed by the late initiation of cyclosporine on post-operative Day 4. METHODS: Between September 1998 and December 1999, we treated 25 patients at risk for post-operative renal dysfunction (high-risk basiliximab group) with the new induction regimen and another 33 patients not at risk (low-risk CsA group) for renal dysfunction with our standard cyclosporine protocol. We identified a historical control group (1996 through 1998) of 32 patients at risk for renal dysfunction (high-risk CsA group) who had received our standard cyclosporine protocol. RESULTS: The increase in serum creatinine levels after transplantation was less in the high-risk basiliximab group (-0.1 +/- 0.7) than in the high-risk CsA group (0.5 +/- 1.0, p < 0.02) and comparable to the low-risk CsA group (0.03 +/- 0.6). The basiliximab protocol did not increase rejection; the percentage of rejection episodes was high-risk basiliximab, 0; high-risk CsA, 13; and low-risk CsA, 3 (p = .13). CONCLUSION: Basiliximab induction therapy allows delayed initiation of cyclosporine after cardiac transplantation without an increase in rejection and reduces the risk of post-operative renal dysfunction.

Adult↗
PubMed2004

Responsiveness of the quality of life in late-stage dementia scale to psychotropic drug treatment in late-stage dementia.

BACKGROUND: We report on the responsiveness of a previously validated quality-of-life scale, the Quality of Life in Late-Stage Dementia scale (QUALID), as an outcome measure in a clinical trial of two psychotropic medications. METHODS: Secondary analyses were conducted comparing outcome measures used in a randomized double-blind trial of two antipsychotics (olanzapine and risperidone) for the treatment of dementia-related behavioral symptoms. The QUALID was completed for 31 of the patients in addition to several measures of behavior-related dementia symptoms including the Neuropsychiatric Inventory, the Withdrawn Behavior subscale of the Multidimensional Observation Scale for Elderly Subjects, the Mini-Mental State Examination, and the Clinical Global Impression. Measures of safety and adverse effects included the Simpson-Angus Scale and records of specific adverse events. RESULTS: A significant positive relationship was found between QUALID score and improvement in behavioral symptoms, and a negative association was found with adverse medication effects. CONCLUSIONS: The QUALID was sensitive to both the treatment effects and the adverse effects of medication in this sample of patients.

Aged↗
PubMed2004

Deep vein harvest: predicting need for fasciotomy.

OBJECTIVE: Deep thigh veins, including the superficial femoral, superficial femoropopliteal, and profunda femoris veins, are versatile autogenous conduits for arterial reconstruction. Although late venous complications are unusual, deep vein harvest may induce severe venous hypertension and predispose the limb to acute compartment syndrome. The purpose of this study was to define the frequency of fasciotomy in patients undergoing deep vein harvest and to identify clinical predictors of the need for fasciotomy after deep vein harvest. METHODS: Over 9 years, 162 patients underwent arterial reconstruction with deep vein harvested from 264 limbs. Indications for deep vein harvest included aortofemoral reconstruction in 127 patients, brachiocephalic arterial reconstruction in 22 patients, and visceral arterial reconstruction in 13 patients. RESULTS: Fasciotomy was performed in 47 of 264 limbs (17.8%) after deep vein harvest. The prevalence of fasciotomy after deep vein harvest was 20.6% for patients requiring aortofemoral reconstruction, whereas no patients underwent fasciotomy after deep vein harvest for mesenteric or brachiocephalic arterial reconstruction (P =.0068). Fasciotomy was performed in 20.7% of limbs after complete deep vein harvest to a level below the adductor hiatus, but no fasciotomies were performed in patients undergoing subtotal deep vein harvest, ending above the adductor hiatus (P =.0023). The mean preoperative ankle-brachial index (ABI) was significantly lower in limbs requiring fasciotomy (ABI, 0.39 +/- 0.05), compared with patients who did not require fasciotomy (ABI, 0.79 +/- 0.02; P <.0001). Fasciotomy was performed in 76.0% of limbs undergoing concurrent ipsilateral greater saphenous vein (GSV) and deep vein harvest, compared with 11.7% of patients undergoing deep vein harvest alone (P <.0001). The mean volume of intraoperative fluid administered to patients requiring fasciotomy was almost 50% higher than the fluid resuscitation received by patients who did not require fasciotomy (9.6 +/- 1.2 L vs 6.5 +/- 0.6 L; P <.0001). Logistic regression analysis determined that lower preoperative ABI (odds ratio [OR], 60.1; 95% confidence interval [CI], 12.5-289.3; P <.0001) and concurrent harvest of the ipsilateral GSV (OR, 9.9; 95% CI, 3.1-31.3; P <.0001) were predictors of the need for fasciotomy. CONCLUSIONS: One in four patients undergoing deep vein harvest for aortofemoral reconstruction may be expected to develop acute compartment syndrome and require fasciotomy. The risk appears to be greatest in patients with severe lower extremity ischemia and in patients undergoing simultaneous GSV and deep vein harvest. Prophylactic fasciotomy may be appropriate in patients with both risk factors, but vigilance for the development of compartment syndrome after deep vein harvest is required in all patients undergoing deep vein harvest for aortofemoral reconstruction.

Compartment Syndromes↗