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Biomedical subjects

M A Smith

Publications and source records attributed to M A Smith.

At least 19 recordsLinked to original sources
PubMed2006

Neighborhood environment and risk of ischemic stroke: the brain attack surveillance in Corpus Christi (BASIC) Project.

The authors explored whether neighborhood-level characteristics are associated with ischemic stroke and whether the association differs by ethnicity, age, and gender. Using data from the Brain Attack Surveillance in Corpus Christi Project (January 2000-June 2003), they identified cases of ischemic stroke (n = 1,247) from both hospital and out-of-hospital sources. Census tracts served as proxies for neighborhoods, and neighborhood socioeconomic status scores were constructed from census variables (higher scores represented less disadvantage). In Poisson regression analyses comparing the 90th percentile of neighborhood score with the 10th, the relative risk of stroke was 0.49 (95% confidence interval (CI): 0.41, 0.58). After adjustment for age, gender, and ethnicity, this association was attenuated (relative risk (RR) = 0.79, 95% CI: 0.63, 1.00). There was no ethnic difference in the association of score with stroke (p for interaction = 0.79). Significant effect modification was found for age (p for interaction < 0.001) and gender (p for interaction = 0.04), with increasing scores being protective against stroke in men and younger persons. Associations were attenuated after adjustment for education (men: RR = 0.77, 95% CI: 0.55, 1.07; persons aged <65 years: RR = 0.65, 95% CI: 0.41, 1.02). Neighborhood characteristics may influence stroke risk in certain gender and age groups. Mechanisms for these associations should be examined.

Age Factors↗
PubMed2006

The effect of experience on detectability in local area anatomical noise.

The aim of this study was to investigate if the ability to detect clinically relevant signals, within local area clinically relevant texture, is related to experience. A two alternative forced choice interleaved staircase experiment was conducted on 101 observers split into three groups; group 1 with diagnostic experience, group 2 with experience of imaging but not of making a diagnosis and group 3 with no experience of imaging. Thresholds of detection within synthesized, clinically representative textures were measured for a 15 mm simulated lesion within an MR T1 weighted brain texture and a 2.5 mm diameter simulated lesion embedded within X-ray trabecular bone texture. The results showed that there was a significant difference in threshold detectability between the groups for the brain texture at the 95% significance level but not for the bone texture. The experienced group did not demonstrate a correlation between their bone and brain results. However, the inexperienced group had a significant correlation between the bone and brain results. There was a significant correlation between increasing experience and detectability but this was dependent on the composition of the local area anatomical noise.

Adult↗
PubMed2006

Projected costs of ischemic stroke in the United States.

BACKGROUND: There are barriers to acute stroke care in minority groups as well as a higher incidence of ischemic stroke when compared with non-Hispanic whites. OBJECTIVE: To estimate the future economic burden of stroke in non-Hispanic whites, Hispanics, and African Americans in the United States from 2005 to 2050. METHODS: We used U.S. Census estimates of the race-ethnic group populations age 45 years and older. We obtained stroke epidemiology and service utilization data from the Northern Manhattan Stroke Study and the Brain Attack Surveillance in Corpus Christi project and other published data. We estimated costs directly from Medicare reimbursement or from studies that used Medicare reimbursement. Direct and indirect costs considered included ambulance services, initial hospitalization, rehabilitation, nursing home costs, outpatient clinic visits, drugs, informal caregiving, and potential lost earnings. RESULTS: The total cost of stroke from 2005 to 2050, in 2005 dollars, is projected to be 1.52 trillion dollars for non-Hispanic whites, 313 billion dollars for Hispanics, and 379 billion dollars for African Americans. The per capita cost of stroke estimates are highest in African Americans (25,782 dollars), followed by Hispanics (17,201 dollars), and non-Hispanic whites (15,597 dollars). Loss of earnings is expected to be the highest cost contributor in each race-ethnic group. CONCLUSIONS: The economic burden of stroke in African Americans and Hispanics will be enormous over the next several decades. Further efforts to improve stroke prevention and treatment in these high stroke risk groups are necessary.

Black or African American↗
PubMed2006

Brain and brawn: parallels in oxidative strength.

Neuronal oxidative stress occurs early in the progression of Alzheimer disease (AD), significantly before the development of the pathologic hallmarks, neurofibrillary tangles, and senile plaques. Study of Down syndrome, cases with autosomal dominant mutation, and sporadic AD all suggest amyloid-beta deposition and hyperphosphorylated tau function as compensatory responses and downstream adaptations to ensure that neuronal cells do not succumb to oxidative damage. Amyloid-beta and tau hyperphosphorylation also define vulnerable muscle cells in sporadic inclusion-body myositis (s-IBM). The role of the structural changes of s-IBM, as in AD, remains to be determined but may mark a critical response yielding a novel balance in oxidant homeostasis.

Adaptation, Physiological↗
PubMed2006

Differences in intracerebral hemorrhage between Mexican Americans and non-Hispanic whites.

BACKGROUND: Mexican Americans (MAs) have higher incidence rates of intracerebral hemorrhage (ICH) than non-Hispanic whites (NHWs). The authors present clinical and imaging characteristics of ICH in MAs and NHWs in a population-based study. METHODS: This work is part of the Brain Attack Surveillance in Corpus Christi (BASIC) project. Cases of nontraumatic ICH were identified from 2000 to 2003. Multivariable logistic regression was used to assess the independent associations between ethnicity and ICH location (lobar vs nonlobar) and volume (> or = 30 vs < 30 mL), adjusting for demographics and baseline clinical characteristics. Logistic regression was also used to determine the association between ethnicity and in-hospital mortality, adjusting for confounders. RESULTS: A total of 149 MAs and 111 NHWs with ICH were identified. MAs were younger (70 vs 77, p < 0.001), more often male (55% vs 42%, p = 0.04), had a lower prevalence of atrial fibrillation (2.0% vs 13%, p < 0.001), and a higher prevalence of diabetes (39% vs 19%, p < 0.001). MA ethnicity was independently associated with nonlobar hemorrhage (OR 2.08, 95% CI: 1.15, 3.70). MAs had over two times the odds of having small (< 30 mL) hemorrhages compared with NHWs (OR = 2.41, 95% CI: 1.31, 4.46). NHWs had higher in-hospital mortality, though this association was no longer significant after adjustment for ICH volume, location, age, and sex. CONCLUSIONS: There are significant differences in the characteristics of ICH in MAs and NHWs, with MA patients more likely to have smaller, nonlobar hemorrhages. These differences may be used to examine the underlying pathophysiology of ICH.

Age of Onset↗
PubMed2006

Presentation of intracerebral haemorrhage in a community.

BACKGROUND: Studies on intracerebral haemorrhage (ICH) from tertiary care centres may not be an accurate representation of the true spectrum of disease presentation. OBJECTIVE: To describe the clinical and imaging presentation of ICH in a community devoid of the referral bias of an academic medical centre; and to investigate factors associated with lower Glasgow coma scale (GCS) score at presentation, as GCS is crucial to early clinical decision making. METHODS: The study formed part of the BASIC project (Brain Attack Surveillance in Corpus Christi), a population based stroke surveillance study in a bi-ethnic Texas community. Cases of first non-traumatic ICH were identified from years 2000 to 2003, using active and passive surveillance. Clinical data were collected from medical records by trained abstractors, and all computed tomography (CT) scans were reviewed by a study physician. Multivariable linear regression was used to identify clinical and CT predictors of a lower GCS score. RESULTS: 260 cases of non-traumatic ICH were identified. Median ICH volume was 11 ml (interquartile range 3 to 36) with hydrocephalus noted in 45%. Median initial GCS score was 12.5 (7 to 15). Hydrocephalus score (p = 0.0014), ambient cistern effacement (p = 0.0002), ICH volume (p = 0.014), and female sex (p = 0.024) were independently associated with lower GCS score at presentation, adjusting for other variables. CONCLUSIONS: ICH has a wide range of severity at presentation. Hydrocephalus is a potentially reversible cause of a lower GCS score. Since early withdrawal of care decisions are often based on initial GCS, recognition of the important influence of hydrocephalus on GCS is warranted before withdrawal of care decisions are made.

Aged↗
PubMed2006

Overprescribing of lipid lowering agents.

BACKGROUND: Undertreatment of hyperlipidemia has received considerable attention. However, little is known about trends in overprescribing of lipid lowering agents. We examined these trends and their associations with physician, practice, and organisational factors. METHODS: 2034 physicians were surveyed twice: baseline (1996-7) and follow up (1998-9). On each occasion they were asked: "For what percentage of 50 year old men without other cardiac risk factors would you recommend an oral agent for total cholesterol of 240, LDL 150, and HDL 50 after 6 months on a low cholesterol diet?" During the survey period the National Cholesterol Education Program guidelines did not recommend prescribing for these patients. Binomial and multinomial logistic regressions assessed baseline overprescribing and longitudinal changes in overprescribing, accounting for complex sampling. RESULTS: 39% of physicians recommended prescribing at baseline (round 1), increasing at follow up (round 2) to 51% (p < 0.001). Physicians who were more likely to overprescribe at baseline were less likely to be board certified (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.38 to 0.63; p < 0.001), were in solo or two-physician practices (OR 1.88, 95% CI 1.46 to 2.41; p < 0.001), had more revenue from Medicare (OR 1.10, 95% CI 1.03 to 1.17; p = 0.004) or Medicaid (OR 1.09, 95% CI 1.01 to 1.18; p = 0.03), or were family physicians (OR 1.87, 95% CI 1.35 to 2.58; p < 0.001). Physicians with large increases in overprescibing were more likely than those with small increases in overprescribing to be international medical graduates (OR 2.09, 95% CI 1.20 to 3.64; p = 0.011) and to spend more hours in patient care (OR 1.14, 95% CI 1.03 to 1.26; p = 0.016). CONCLUSIONS: Overprescribing of lipid lowering agents is commonplace and increased. At baseline and longitudinally, overprescribing was primarily associated with physician and practice characteristics and not with organisational factors.

Cholesterol, HDL↗
PubMed2006

Effect of fat content on infection by Listeria monocytogenes in a mouse model.

An estimated 2,500 cases of listeriosis occur annually in the United States. Listeriosis is particularly severe among pregnant women and immunocompromised individuals. Little is known regarding the effect of the food matrix on the ability of L. monocytogenes to survive in the gastrointestinal tract and cause systemic infection. Mice were inoculated with various doses of L. monocytogenes in skim milk, Half & Half, or whipping cream to determine whether differences in milk fat content influence the ability of L. monocytogenes to survive passage through the gut and infect the liver or spleen. The number of fecal samples positive for L. monocytogenes increased with increasing doses of L. monocytogenes for all three vehicles. The number of L. monocytogenes cells isolated from liver or spleen of mice dosed with L. monocytogenes was not significantly different among treatment vehicles. Dose-response models revealed that as the dosage of L. monocytogenes was increased in different milk vehicles, the number of L. monocytogenes cells in liver or spleen also increased. Although fat content of food had no dose-dependent effect on L. monocytogenes infection in the murine gastrointestinal tract, we cannot discount the possibility that it may be a factor in L. monocytogenes infections of humans because of differences in the physiology of gastrointestinal tracts of mice and humans.

Animals↗
PubMed2006

A scoring system for ascertainment of incident stroke; the Risk Index Score (RISc).

OBJECTIVES: The main objective of this study was to develop and validate a computer-based statistical algorithm that could be translated into a simple scoring system in order to ascertain incident stroke cases using hospital admission medical records data. METHODS: The Risk Index Score (RISc) algorithm was developed using data collected prospectively by the Brain Attack Surveillance in Corpus Christi (BASIC) project, 2000. The validity of RISc was evaluated by estimating the concordance of scoring system stroke ascertainment to stroke ascertainment by physician and/or abstractor review of hospital admission records. RESULTS: RISc was developed on 1718 randomly selected patients (training set) and then statistically validated on an independent sample of 858 patients (validation set). A multivariable logistic model was used to develop RISc and subsequently evaluated by goodness-of-fit and receiver operating characteristic (ROC) analyses. The higher the value of RISc, the higher the patient's risk of potential stroke. The study showed RISc was well calibrated and discriminated those who had potential stroke from those that did not on initial screening. CONCLUSION: In this study we developed and validated a rapid, easy, efficient, and accurate method to ascertain incident stroke cases from routine hospital admission records for epidemiologic investigations. Validation of this scoring system was achieved statistically; however, clinical validation in a community hospital setting is warranted.

Aged↗
PubMed2005

Differential induction of PPAR-gamma by luminal glutamine and iNOS by luminal arginine in the rodent postischemic small bowel.

Using a rodent model of gut ischemia-reperfusion (I/R), we have previously shown that the induction of inducible nitric oxide synthase (iNOS) is harmful, whereas the induction of heme oxygenase 1 (HO-1) and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is protective. In the present study, we hypothesized that the luminal nutrients arginine and glutamine differentially modulate these molecular events in the postischemic gut. Jejunal sacs were created in rats at laparotomy, filled with either 60 mM glutamine, arginine, or magnesium sulfate (osmotic control) followed by 60 min of superior mesenteric artery occlusion and 6 h of reperfusion, and compared with shams. The jejunum was harvested for histology or myeloperoxidase (MPO) activity (inflammation). Heat shock proteins and iNOS were quantitated by Western blot analysis and PPAR-gamma by DNA binding activity. In some experiments, rats were pretreated with the PPAR-gamma inhibitor G9662 or with the iNOS inhibitor N-[3(aminomethyl)benzyl]acetamidine (1400W). iNOS was significantly increased by arginine but not by glutamine following gut I/R and was associated with increased MPO activity and mucosal injury. On the other hand, PPAR-gamma was significantly increased by glutamine but decreased by arginine, whereas heat shock proteins were similarly increased in all experimental groups. The PPAR-gamma inhibitor G9662 abrogated the protective effects of glutamine, whereas the iNOS inhibitor 1400W attenuated the injurious effects of arginine. We concluded that luminal arginine and glutamine differentially modulate the molecular events that regulate injurious I/R-mediated gut inflammation and injury. The induction of PPAR-gamma by luminal glutamine is a novel protective mechanism, whereas luminal arginine appears harmful to the postischemic gut due to enhanced expression of iNOS.

Animals↗
PubMed2005

Dissociation and ionization of H+2 by ultrashort intense laser pulses probed by coincidence 3D momentum imaging.

Laser-induced dissociation and ionization of H(+)(2) were simultaneously measured using coincidence 3D momentum imaging, allowing direct separation of the two processes, even where the fragment kinetic energy is the same for both processes. The results for 45 and 135 fs 790 nm pulses with an intensity of approximately 2.5 x 10(14) W/cm(2) differ from each other much more than one would expect from previous measurements with longer pulses. Ionization was negligible for the longer pulse and was strongly aligned along the laser polarization for the shorter pulse, but showed no structure in its kinetic energy distribution. In addition, the ionization to dissociation ratio was found to be much smaller than theoretically predicted for H(+)(2).

Journal Article↗
PubMed2005

Evaluation of the dosimetric performance of BANG3 polymer gel.

New radiotherapy techniques call for three-dimensional dosimetric methods with high spatial resolution. Radiation sensitive gels read out using MRI T(2) mapping provide an extremely promising option, and commercially available BANG polymer gels provide a convenient route into gel dosimetry. Gel dosimetry is dependent on the ability to calibrate gel response against radiation dose. This in turn is dependent on the reproducibility of response both between gels irradiated to the same dose and for a single gel sample over time. This study aims to evaluate the performance of a commercially available BANG gel. Our experimental arrangement gave excellent precision of radiation delivery (<0.2%) and reproducibility of T(2) measurement (<0.5%). Seven groups of 10 test tubes containing BANG3 gel were irradiated in 0.5 Gy steps between 0 and 3 Gy. A further four groups of four samples were irradiated in 2 Gy steps between 4 and 10 Gy. The gel samples were identical and derived from the same manufacturing batch. MR imaging was carried out four days after irradiation and then at weekly intervals for four weeks. Short-term variation in gel response can readily be corrected using reference samples. Longer term systematic drift of the gel calibration curve was observed relative to reference samples prepared in-house for quality assurance purposes. This implies that read-out of the calibration gels and dosimetry phantom must be performed at the same time after irradiation, or errors of up to 25% may be incurred. Precision of gel response did not change significantly over time. The observation of significantly different T(2) values both prior to irradiation and following irradiation to the same dose (variation up to 15%) illustrates the current difficulties associated with BANG3 gel calibration and constrains the practical utility of these commercially available gels for clinical radiation dosimetry.

Dose-Response Relationship, Radiation↗
PubMed2005

Retinoic acid isomers protect hippocampal neurons from amyloid-beta induced neurodegeneration.

Attenuating amyloid-beta mediated neurodegeneration is of major therapeutic consideration in the potential treatment of Alzheimer disease. Previously, we found that a high dietary consumption of retinoic acid was associated with a reduced incidence of Alzheimer disease. Therefore, in this study, we investigated whether amyloid-beta mediated cell death in primary hippocampal neurons could be prevented by retinoic acid isomers. Our results suggest that retinoic acid isomers, including all-trans retinoic acid, 9-cis retinoic acid, and 13-cis retinoic acid, may play an important role in protecting neurons from amyloid-beta -induced cell death. Retinoic acid may therefore afford a novel therapeutic mechanism for the treatment and prevention of Alzheimer disease.

Alitretinoin↗
PubMed2005

Evidence for the role of gonadotropin hormones in the development of Alzheimer disease.

Differences in the prevalence and age of onset of Alzheimer disease (AD) in men and women, and observations that hormone replacement therapy (HRT) may prevent the development of AD, caused many to hypothesize that estrogen deficiency contributes to AD. However, recent trials using estrogen failed to show any benefit in preventing or alleviating the disease. To address this and other inconsistencies in the estrogen hypothesis, we suspect that another hormone of the hypothalamic-pituitary-gonadal axis, luteinizing hormone (LH), as a major factor in AD pathogenesis. Individuals with AD have elevated levels of LH when compared with controls, and both LH and its receptor are present in increased quantities in brain regions susceptible to degeneration in AD. LH is also known to be mitogenic, and could therefore initiate the cell cycle abnormalities known to be present in AD-affected neurons. In cell culture, LH increases amyloidogenic processing of amyloid-beta protein precursor, and in animal models of AD, pharmacologic suppression of LH and FSH reduces plaque formation. Given the evidence supporting a pathogenic role for LH in AD, a trial of leuprolide acetate, which suppresses LH release, has been initiated in patients.

Aging↗
PubMed2005

No increase in rejection or graft loss in kidney transplant recipients with thrombophilia treated with anticoagulation and triple immunosuppression.

INTRODUCTION: Recent studies from Europe have demonstrated that patients with end-stage renal disease who receive a kidney transplant are at an increased risk for rejection and graft loss when compared with patients who have no known thrombophilia. The role of anticoagulation has not been investigated in these patients. MATERIALS AND METHODS: We prospectively tested patients who were evaluated for a kidney transplant for 8 thrombophilias, protein S and C deficiencies, factor V Leiden mutation, antithrombin III deficiency, anticardiolipin antibody, lupus anticoagulant, prothrombin gene mutation, and heparin-induced platelet antibody (HIPA). Patients with any identified thrombophilia received heparin or argatroban (for HIPA (+) patients) followed by coumadin for 1 year after transplantation. Triple therapy included cyclosporine, prednisone, and CellCept (Roche Pharmaceuticals, Nutley, NJ, USA). Sensitized, black, or repeat transplantation patients received induction with an interleukin (IL)-2 inhibitor. Data were collected in a retrospective manner. Rejection was biopsy-proven. RESULTS: Of the 112 transplant recipients who were tested for thrombophilia, 37 had 1 or more thrombophilia and 75 had no thrombophilia identified. Twenty-six patients received heparin and 11 received argatroban. There were no differences in recipient age, cold storage time, graft loss, HLA match, rejection episodes, 1-year graft survival, or serum creatinine level at 1 year. Significant differences were noted in posttransplantation bleeding, 35% versus 5%, and delayed graft function, 32% versus 15%, in patients with thrombophilia versus no thrombophilia, respectively. CONCLUSION: This is the first study to demonstrate that there is no increase in rejection or graft loss in kidney transplant recipients with thrombophilia when treated with anticoagulation and triple immunosuppression.

Anticoagulants↗
PubMed2005

Evaluation of the clinical efficacy of prokinetic drugs in the management of post-operative ileus: can retrospective data help us?

The objectives of the study were to determine whether retrospective data can be used to answer questions about the efficacy of prokinetic agents when used to treat horses with post-operative ileus (POI). We describe prevalence and mortality of POI with reference to treatment with four prokinetic agents. By combining data from two Hospitals a study population of 55 horses with POI following pedunculated lipoma obstruction (PLO) was established. Univariable and multivariable associations were determined between short term survival and potential explanatory variables. With death as outcome in multivariable models, breed and hospital were significantly associated with outcome but the use of prokinetic agents was not (P=0.15). However, sample size estimates indicate the low power of this study to detect differences in outcome. It was not possible definitively to evaluate the efficacy of prokinetics as treatment for POI following PLO using retrospective data. The data were suggestive of limited efficacy of prokinetics as treatment for POI. It is postulated that the identified association between hospital and survival reflects differences in clinician decision making. The study highlights the need for further prospective studies using randomised clinical trials to evaluate accurately the efficacy of prokinetic agents. This report illustrates difficulties with performing retrospective analysis of clinical data to determine the efficacy of treatment regimes.

Animals↗
PubMed2005

Beta-site APP cleaving enzyme up-regulation induced by 4-hydroxynonenal is mediated by stress-activated protein kinases pathways.

4-Hydroxynonenal (HNE), an aldehydic product of lipid peroxidation, up-regulates expression of the beta-site APP cleaving enzyme (BACE-1), an aspartyl protease responsible for the beta-secretase cleavage of amyloid precursor protein (AbetaPP), and results in increased levels of amyloid beta (Abeta) peptide. The mechanisms underlying this remain unclear but are of fundamental importance because prevention of BACE-1 up-regulation is viewed as an important therapeutic strategy. In this study, we exposed NT(2) neurons to a range of HNE concentrations (0.5-5 microm) that elicited an up-regulation of BACE-1 expression, a significant increase in intracellular and secreted levels of Abeta peptides as well as apoptosis involving poly-ADP ribose polymerase cleavage and activation of caspase 3. To delineate the molecular events involved in HNE-mediated BACE-1 activation, we investigated the involvement of stress-activated protein kinases (SAPK), signal transducers and activators of transcription (STAT) and serine-threonine kinase B/phosphatidylinositol phosphate 3 kinase (Akt/PtdIns3K). Using specific pharmacological inhibitors, our results show that activation of c-Jun N-terminal kinases and p38(MAPK.), but not STAT or Akt/PtdIns3K, pathways mediate the HNE-dependent up-regulation of BACE-1 expression. Therefore, HNE, an oxidative stress mediator detected in vivo in the brains of Alzheimer's disease patients, may play a pathogenetic role in Alzheimer's disease by selectively activating SAPK pathways and BACE-1 that regulate the proteolytic processing of AbetaPP.

Aldehydes↗