Showing papers by "Saint Louis University published in 2000"

The mini-cog: a cognitive 'vital signs' measure for dementia screening in multi-lingual elderly.

Abstract: Objectives. The Mini-Cog, a composite of three-item recall and clock drawing, was developed as a brief test for discriminating demented from non-demented persons in a community sample of culturally, linguistically, and educationally heterogeneous older adults. Subjects. All 129 who met criteria for probable dementia based on informant interviews and 120 with no history of cognitive decline were included; 124 were non-English speakers. Methods. Sensitivity, specificity, and diagnostic value of the Mini-Cog were compared with those of the Mini-Mental State Exam (MMSE) and Cognitive Abilities Screening Instrument (CASI). Results. The Mini-Cog had the highest sensitivity (99%) and correctly classified the greatest percentage (96%) of subjects. Moreover, its diagnostic value was not influenced by education or language, while that of the CASI was adversely influenced by low education, and both education and language compromised the diagnostic value of the MMSE. Administration time for the Mini-Cog was 3 minutes vs 7 minutes for the MMSE. Conclusions. The Mini-Cog required minimal language interpretation and training to administer, and no test forms of scoring modifications were needed to compensate for the extensive linguistic and educational heterogeneity of the sample. Validation in clinical and population-based samples is warranted, as its brevity and ease of administration suggest that the Mini-Cog might be readily incorporated into general practice and senior care settings as a routine ‘cognitive vital signs’ measure. Copyright © 2000 John Wiley & Sons, Ltd.

Humanized xenobiotic response in mice expressing nuclear receptor SXR.

Abstract: The cytochrome CYP3A gene products, expressed in mammalian liver, are essential for the metabolism of lipophilic substrates, including endogenous steroid hormones and prescription drugs. CYP3A enzymes are extremely versatile and are inducible by many of their natural and xenobiotic substrates. Consequently, they form the molecular basis for many clinical drug-drug interactions. The induction of CYP3A enzymes is species-specific, and we have postulated that it involves one or more cellular factors, or receptor-like xeno-sensors. Here we identify one such factor unequivocally as the nuclear receptor pregnenolone X receptor (PXR) and its human homologue, steroid and xenobiotic receptor (SXR). We show that targeted disruption of the mouse PXR gene abolishes induction of CYP3A by prototypic inducers such as dexamethasone or pregnenolone-16alpha-carbonitrile. In transgenic mice, an activated form of SXR causes constitutive upregulation of CYP3A gene expression and enhanced protection against toxic xenobiotic compounds. Furthermore, we show that the species origin of the receptor, rather than the promoter structure of CYP3A genes, dictates the species-specific pattern of CYP3A inducibility. Thus, we can generate 'humanized' transgenic mice that are responsive to human-specific inducers such as the antibiotic rifampicin. We conclude that SXR/PXR genes encode the primary species-specific xeno-sensors that mediate the adaptive hepatic response, and may represent the critical biochemical mechanism of human xenoprotection.

Idiopathic Short QT Interval:A New Clinical Syndrome?

Abstract: In this first clinical report of an idiopathic familial persistently short QT interval (QTI), we describe three members of one family (a 17-year-old female, her 21-year-old brother, and their 51-year-old mother) demonstrating this ECG phenomenon, associated in the 17-year-old with several episodes of paroxysmal atrial fibrillation requiring electrical cardioversion. Similar ECG changes seen in an unrelated 37-year-old patient were associated with sudden cardiac death. Our report also describes other manifestations of abnormal shortening of the QTI and considers the possible arrhythmogenic potential of the short QTI.

Joint inversion of receiver function and surface wave dispersion observations

Abstract: We implement a method to invert jointly teleseismic P-wave receiver functions and surface wave group and phase velocities for a mutually consistent estimate of earth structure. Receiver functions are primarily sensitive to shear wave velocity contrasts and vertical traveltimes, and surface wave dispersion measurements are sensitive to vertical shear wave velocity averages. Their combination may bridge resolution gaps associated with each individual data set. We formulate a linearized shear velocity inversion that is solved using a damped least-squares scheme that incorporates a priori smoothness constraints for velocities in adjacent layers. The data sets are equalized for the number of data points and physical units in the inversion process. The combination of information produces a relatively simple model with a minimal number of sharp velocity contrasts. We illustrate the approach using noise-free and realistic noise simulations and conclude with an inversion of observations from the Saudi Arabian Shield. Inversion results for station SODA, located in the Arabian Shield, include a crust with a sharp gradient near the surface (shear velocity changing from 1.8 to 3.5 km s−1 in 3 km) underlain by a 5-km-thick layer with a shear velocity of 3.5 km s−1 and a 27-km-thick layer with a shear velocity of 3.8 km s−1, and an upper mantle with an average shear velocity of 4.7 km s−1. The crust–mantle transition has a significant gradient, with velocity values varying from 3.8 to 4.7 km s−1 between 35 and 40 km depth. Our results are compatible with independent inversions for crustal structure using refraction data.

How does physician advice influence patient behavior? Evidence for a priming effect.

Abstract: Results: Patients who received physician advice to quit smoking, eat less fat, or get more exercise prior to receiving intervention materials on the same topic were more likely to remember the materials, show them to others, and perceive the materials as applying to them specifically. They were also more likely to report trying to quit smoking (odds ratio [OR] = 1.54, 95% confidence interval [CI] = 0.95-2.40), quitting for at least 24 hours (OR = 1.85, 95% CI = 1.02-3.34), and making some changes in diet (OR = 1.35, 95% CI = 1.00-1.84) and physical activity (OR = 1.51, 95% CI = 0.95-2.40). Conclusions: Findings support an integrated model of disease prevention in which physician advice is a catalyst for change and is supported by a coordinated system of information and activities that can provide the depth of detail and individualization necessary for sustained behavioral change. Arch Fam Med. 2000;9:426-433

Common genetic vulnerability for pathological gambling and alcohol dependence in men

Abstract: Background In comparison with alcohol dependence (AD), relatively little is known about the causes of pathological gambling (PG). Given the high rate of comorbidity between PG and AD, knowledge about the causes of AD may be applied to understanding those of PG. Methods Subjects were adult male twin pairs from the Vietnam Era Twin Registry. Lifetime histories of PG and AD were assessed by structured psychiatric telephone interview. The validity of a continuum of PG liability was tested to determine whether the causes of subclinical PG, or problem gambling, are quantitatively or qualitatively distinct from those of DSM-III-R PG disorder. Genetic model-fitting methods were used to quantify the extent to which the genetic and environmental risk for PG could be explained by the risk for AD. Results Tests of the continuity model of PG were all consistent with the hypothesis that subclinical PG and DSM-III-R PG disorder have many, perhaps all, of the same risk factors and thus differ quantitatively rather than qualitatively. Depending on the PG definition, between 12% and 20% of the genetic variation and between 3% and 8% of the nonshared environmental variation in the risk for PG were accounted for by the risk for AD. Conclusions Subclinical PG, or problem gambling, may be a milder form of PG, rather than an etiologically distinct syndrome. Risk for AD accounts for a significant but modest proportion of the genetic and environmental risk for subclinical PG and DSM-III-R PG disorder.

Patterns and correlates of physical activity among US women 40 years and older.

Abstract: OBJECTIVES: This study describes the patterns of physical activity among minority women by using a variety of definitions and determines sociodemographic and behavioral correlates of physical activity in this population. METHODS: A cross-sectional study was conducted in 1996 and 1997 among US women 40 years and older (n = 2912) of the following racial/ethnic groups: African American, American Indian/Alaskan Native, Hispanic, and White. RESULTS: Physical activity was lowest among African Americans and American Indians/Alaskan Natives (adjusted odds ratios [ORs] for no leisure-time activity were 1.35 [95% confidence interval (CI) = 1.08, 1.68] and 1.65 [95% CI = 1.33, 2.06], respectively). A much higher proportion of women were classified as being physically active when occupational activity rather than more traditional assessments of leisure activity were used to determine level of physical activity. On the basis of a composite definition of physical activity, 72% of respondents reported being physically active. Women living in rural regions (OR = 1.33; 95% CI = 1.12, 1.58) were more likely than urban inhabitants to be completely inactive during leisure time. CONCLUSIONS: Minority women are among the least active subgroups in American society, although not all groups are less active than White women when all domains of physical activity are taken into account.

Risk factors for morbidity and mortality after colectomy for colon cancer

Abstract: PURPOSE: Comorbid conditions affect the risk of adverse outcomes after surgery, but the magnitude of risk has not previously been quantified using multivariate statistical methods and prospectively collected data. Identifying factors that predict results of surgical procedures would be valuable in assessing the quality of surgical care. This study was performed to define risk factors that predict adverse events after colectomy for cancer in Department of Veterans Affairs Medical Centers. METHODS: The National Veterans Affairs Surgical Quality Improvement Program contains prospectively collected and extensively validated data on more than 415,000 surgical operations. All patients undergoing colectomy for colon cancer from 1991 to 1995 who were registered in the National Veterans Affairs Surgical Quality Improvement Program database were selected for study. Independent variables examined included 68 preoperative and 12 intraoperative clinical risk factors; dependent variables were 21 specific adverse outcomes. Stepwise logistic regression analysis was used to construct models predicting the 30-day mortality rate and 30-day morbidity rates for each of the ten most frequent complications. RESULTS: A total of 5,853 patients were identified; 4,711 (80 percent) underwent resection and primary anastomosis. One or more complications were observed in 1,639 of 5,853 (28 percent) patients. Prolonged ileus (439/5,853; 7.5 percent), pneumonia (364/5,853; 6.2 percent), failure to wean from the ventilator (334/5,853; 5.7 percent), and urinary tract infection (292/5,853; 5 percent) were the most frequent complications. The 30-day mortality rate was 5.7 percent (335/5,853). For most complications, 30-day in-hospital mortality rates were significantly higher for patients with a complication than for those without. Thirty-day mortality rates exceeded 50 percent if postoperative coma, cardiac arrest, a pre-existing vascular graft prosthesis that failed after colectomy, renal failure, pulmonary embolism, or progressive renal insufficiency occurred. Preoperative factors that predicted a high risk of 30-day mortality included ascites, serum sodium >145 mg/dl, “do not resuscitate” status before surgery, American Society of Anesthesiologists classes III and IV OR V, and low serum albumin. CONCLUSIONS: Mortality rates after colectomy in Veterans Affairs hospitals are comparable with those reported in other large studies. Ascites, hypernatremia, do not resuscitate status before surgery, and American Society of Anesthesiologists classes III and IV OR V were strongly predictive of perioperative death. Clinical trials to decrease the complication rate after colectomy for colon cancer should focus on these risk factors.

Correlates of Immune Protection Induced by Live, Attenuated, Cold-Adapted, Trivalent, Intranasal Influenza Virus Vaccine

Abstract: The authors conducted a 2-year, multicenter, double-blind, placebo-controlled efficacy field trial of live, attenuated, cold-adapted, trivalent influenza vaccine administered by nasal spray to children 15-71 months old. Overall, vaccine was 92% efficacious at preventing culture-confirmed infection by influenza A/H3N2 and influenza B. Because influenza A/H1N1 did not cause disease during the years in which this study was conducted, the authors sought to determine vaccine efficacy and correlates of immune protection against experimental challenge with 107 TCID50 of attenuated H1N1 (vaccine strain) by intranasal spray. Prechallenge assessments included serum hemaglutination-inhibiting (HAI) antibody and nasal wash IgA antibody to H1N1. Vaccine was 83% efficacious (95% confidence interval, 60%-93%) at preventing shedding of H1N1 virus after challenge. Any serum HAI antibody or any nasal wash IgA antibody was correlated with significant protection from H1N1 infection as indicated by vaccine-virus shedding, and high efficacy against H1N1 challenge was demonstrated.

Co‐branding: brand equity and trial effects

Abstract: Co‐branding is an increasingly popular technique marketers use in attempting to transfer the positive associations of the partner (constituent) brands to a newly formed co‐brand (composite brand). This research examines the effects of co‐branding on the brand equity of both the co‐branded product and the constituent brands that comprise it, both before and after product trial. It appears that co‐branding is a win/win strategy for both co‐branding partners regardless of whether the original brands are perceived by consumers as having high or low brand equity. Although low equity brands may benefit most from co‐branding, high equity brands are not denigrated even when paired with a low equity partner. Further, positive product trial seems to enhance consumers’ evaluations of co‐branded products, particularly those with a low equity constituent brand. Co‐branding strategies may be effective in exploiting a product performance advantage or in introducing a new product with an unfamiliar brand name.

Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial virus vaccine candidate in infancy

Abstract: A live-attenuated, intranasal respiratory syncytial virus (RSV) candidate vaccine, cpts-248/ 404, was tested in phase 1 trials in 114 children, including 37 1-2-month-old infants-a target age for RSV vaccines. The cpts-248/404 vaccine was infectious at 104 and 105 plaque-forming units in RSV-naive children and was broadly immunogenic in children >6 months old. Serum and nasal antibody responses in 1-2 month olds were restricted to IgA, had a dominant response to RSV G protein, and had no increase in neutralizing activity. Nevertheless, there was restricted virus shedding on challenge with a second vaccine dose and preliminary evidence for protection from symptomatic disease on natural reexposure. The cpts-248/404 vaccine candidate did not cause fever or lower respiratory tract illness. In the youngest infants, however, cpts-248/404 was unacceptable because of upper respiratory tract congestion associated with peak virus recovery. A live attenuated RSV vaccine for the youngest infant will use cpts-248/404 modified by additional attenuating mutations.

Environmental Control to Reduce Transmission of Clostridium difficile

Abstract: Restrictive antibiotic policies and infection control measures have been shown to reduce the incidence of Clostridium difficile-associated diarrhea (CDAD) among hospitalized patients. To date, the role of environmental disinfectants in reducing nosocomial CDAD rates has not been well studied. In a before-and-after intervention study, patients in 3 units were evaluated to determine if unbuffered 1:10 hypochlorite solution is effective as an environmental disinfectant in reducing the incidence of CDAD. Among 4252 patients, the incidence rate of CDAD for bone marrow transplant patients decreased significantly, from 8.6 to 3.3 cases per 1000 patient-days (hazard ratio, 0.37; 95% confidence interval, 0.19-0.74), after the environmental disinfectant was switched from quaternary ammonium to 1:10 hypochlorite solution in the rooms of patients with CDAD. Reverting later to quaternary ammonium solution increased the CDAD rate to 8.1 cases per 1000 patient-days. No reduction in CDAD rates was seen among neurosurgical intensive care unit and general medicine patients, for whom baseline rates were 3.0 and 1.3 cases per 1000 patient-days, respectively. Unbuffered 1:10 hypochlorite solution is effective in decreasing patients' risk of developing CDAD in areas where CDAD is highly endemic. Presumed mechanisms include reducing the environmental burden and the potential for C. difficile transmission among susceptible patients.

Transferrin receptor 2: Continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis

Abstract: Hereditary hemochromatosis (HH) is a common autosomal recessive disorder characterized by excess absorption of dietary iron and progressive iron deposition in several tissues, particularly liver. Liver disease resulting from iron toxicity is the major cause of death in HH. Hepatic iron loading in HH is progressive despite down-regulation of the classical transferrin receptor (TfR). Recently a human cDNA highly homologous to TfR was identified and reported to encode a protein (TfR2) that binds holotransferrin and mediates uptake of transferrin-bound iron. We independently identified a full-length murine EST encoding the mouse orthologue of the human TfR2. Although homologous to murine TfR in the coding region, the TfR2 transcript does not contain the iron-responsive elements found in the 3' untranslated sequence of TfR mRNA. To determine the potential role for TfR2 in iron uptake by liver, we investigated TfR and TfR2 expression in normal mice and murine models of dietary iron overload (2% carbonyl iron), dietary iron deficiency (gastric parietal cell ablation), and HH (HFE -/-). Northern blot analyses demonstrated distinct tissue-specific patterns of expression for TfR and TfR2, with TfR2 expressed highly only in liver where TfR expression is low. In situ hybridization demonstrated abundant TfR2 expression in hepatocytes. In contrast to TfR, TfR2 expression in liver was not increased in iron deficiency. Furthermore, hepatic expression of TfR2 was not down-regulated with dietary iron loading or in the HFE -/- model of HH. From these observations, we propose that TfR2 allows continued uptake of Tf-bound iron by hepatocytes even after TfR has been down-regulated by iron overload, and this uptake contributes to the susceptibility of liver to iron loading in HH.

Are tailored health education materials always more effective than non-tailored materials?

Abstract: While promising, the evidence in support of tailored health communication has not been overwhelming. One explanation is that tailored materials may be far superior to non-tailored materials in some cases, but only slightly better, no different or less effective in others. In this study, 198 overweight adults were randomly assigned to receive either tailored or non-tailored weight loss materials. Participants' cognitive, affective and behavioral responses to the materials were measured at an immediate and 1 month follow-up. Analyses compared those who received tailored materials to those who received non-tailored materials that were--by chance alone--either a good fit, moderate fit or poor fit, based on the match between behavioral characteristics of the participant and content of the non-tailored materials. Findings showed that good-fitting non-tailored materials performed as well or better than tailored materials for several cognitive, affective and behavioral outcomes. However, moderate- and poor-fitting non-tailored materials were consistently inferior to both approaches. The art and science of creating tailored health communication programs is still evolving. Data from this study suggest present approaches to tailoring are more effective than non-tailored materials in most, but not all cases. Specific recommendations are made describing ways to refine tailoring methods to maximize the effectiveness of this approach.

Red blood cell regulation of microvascular tone through adenosine triphosphate.

Abstract: The matching of blood flow with metabolic need requires a mechanism for sensing the needs of the tissue and communicating that need to the arterioles, the ultimate controllers of tissue perfusion. ...

Recombinant chimeric yellow fever-dengue type 2 virus is immunogenic and protective in nonhuman primates.

Abstract: A chimeric yellow fever (YF)-dengue type 2 (dengue-2) virus (ChimeriVax-D2) was constructed using a recombinant cDNA infectious clone of a YF vaccine strain (YF 17D) as a backbone into which we inserted the premembrane (prM) and envelope (E) genes of dengue-2 virus (strain PUO-218 from a case of dengue fever in Bangkok, Thailand). The chimeric virus was recovered from the supernatant of Vero cells transfected with RNA transcripts and amplified once in these cells to yield a titer of 6.3 log10 PFU/ml. The ChimeriVax-D2 was not neurovirulent for 4-week-old outbred mice inoculated intracerebrally. This virus was evaluated in rhesus monkeys for its safety (induction of viremia) and protective efficacy (induction of anti-dengue-2 neutralizing antibodies and protection against challenge). In one experiment, groups of non-YF-immune monkeys received graded doses of ChimeriVax-D2; a control group received only the vaccine diluents. All monkeys (except the control group) developed a brief viremia and showed no signs of illness. Sixty-two days postimmunization, animals were challenged with 5.0 log10 focus forming units (FFU) of a wild-type dengue-2 virus. No viremia (<1.7 log10 FFU/ml) was detected in any vaccinated group, whereas all animals in the placebo control group developed viremia. All vaccinated monkeys developed neutralizing antibodies in a dose-dependent response. In another experiment, viremia and production of neutralizing antibodies were determined in YF-immune monkeys that received either ChimeriVax-D2 or a wild-type dengue-2 virus. Low viremia was detected in ChimeriVax-D2-inoculated monkeys, whereas all dengue-2-immunized animals became viremic. All of these animals were protected against challenge with a wild-type dengue-2 virus, whereas all YF-immune monkeys and nonimmune controls became viremic upon challenge. Genetic stability of ChimeriVax-D2 was assessed by continuous in vitro passage in VeroPM cells. The titer of ChimeriVax-D2, the attenuated phenotype for 4-week-old mice, and the sequence of the inserted prME genes were unchanged after 18 passages in Vero cells. The high replication efficiency, attenuation phenotype in mice and monkeys, immunogenicity and protective efficacy, and genomic stability of ChimeriVax-D2 justify it as a novel vaccine candidate to be evaluated in humans.