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Biomedical subjects

Jennifer Anderson

Publications and source records attributed to Jennifer Anderson.

At least 19 recordsLinked to original sources

The affinity of the FimH fimbrial adhesin is receptor-driven and quasi-independent of Escherichia coli pathotypes.

Type-1 fimbriae are important virulence factors for the establishment of Escherichia coli urinary tract infections. Bacterial adhesion to the high-mannosylated uroplakin Ia glycoprotein receptors of bladder epithelium is mediated by the FimH adhesin. Previous studies have attributed differences in mannose-sensitive adhesion phenotypes between faecal and uropathogenic E. coli to sequence variation in the FimH receptor-binding domain. We find that FimH variants from uropathogenic, faecal and enterohaemorrhagic isolates express the same specificities and affinities for high-mannose structures. The only exceptions are FimHs from O157 strains that carry a mutation (Asn135Lys) in the mannose-binding pocket that abolishes all binding. A high-mannose microarray shows that all substructures are bound by FimH and that the largest oligomannose is not necessarily the best binder. Affinity measurements demonstrate a strong preference towards oligomannosides exposing Manalpha1-3Man at their non-reducing end. Binding is further enhanced by the beta1-4-linkage to GlcNAc, where binding is 100-fold better than that of alpha-d-mannose. Manalpha1-3Manbeta1-4GlcNAc, a major oligosaccharide present in the urine of alpha-mannosidosis patients, thus constitutes a well-defined FimH epitope. Differences in affinities for high-mannose structures are at least 10-fold larger than differences in numbers of adherent bacteria between faecal and uropathogenic strains. Our results imply that the carbohydrate expression profile of targeted host tissues and of natural inhibitors in urine, such as Tamm-Horsfall protein, are stronger determinants of adhesion than FimH variation.

Adhesins, Escherichia coli↗

Stereotypy in young children with autism and typically developing children.

Although stereotypy is one of the key diagnostic features of autism, few studies have compared stereotypic behavior in children with autism and typically developing children. The present study employed direct observational measurement methods to assess levels of stereotypic behavior in 2-, 3- and 4-year-old children with autism or pervasive developmental disorder - not otherwise specified (PDD-NOS) and age-matched typically developing peers. Thirty children with autism or PDD-NOS and 30 typically developing children participated. Each child's performance of several early learning and play skills was assessed using a direct observational assessment protocol developed for children with autism who were entering early intensive behavioral treatment. Duration of episodes of vocal and motor stereotypy was recorded from a videotaped 10 min portion of that assessment session. Results indicated that the 2-year-old children with autism or PDD-NOS had somewhat higher levels of stereotypic behavior than the typically developing 2-year-olds, while the 3- and 4-year-old children with autism or PDD-NOS displayed substantially higher levels stereotypic behavior than their same-age peers.

Age Factors↗

Effects of long-term gait training using visual cues in an individual with Parkinson disease.

BACKGROUND AND PURPOSE: In an attempt to improve the gait of people with Parkinson disease (PD), researchers have examined the effect of visual cues placed on the floor. These studies typically have used a single session of training with such cues and have not examined the long-term carryover of such training. In the present study, therefore, gait was analyzed during uncued, cued, and retention phases, each lasting 1 month. SUBJECT: A 78-year-old woman who had been diagnosed with PD 12 years previously (Hoehn and Yahr classification of disability, stage III) volunteered for the study. METHODS: During the initial uncued gait phase, the subject was required to walk a distance of 10 m as many times as she could in 30 minutes, 3 times per week for 4 weeks. During the 4-week cued gait phase, visual cues were placed on the floor along the 10-m walkway. The cues were initially 110% of the uncued step length and were later increased to 120%. Following this cued gait phase, the subject's gait was recorded periodically for 1 month without cues available. Step length, gait speed, and 2-dimensional lower-limb kinematics were compared within and across the 3 experimental phases. Celeration lines were calculated for the initial uncued phase and then extrapolated across the cued training and uncued retention phases. Binomial tests were used to analyze the significance of changes from the initial phase of the experiment. RESULTS: Step length (0.53-0.56 m) and gait speed (0.77-0.82 m x s(-1)) were essentially unchanged during uncued gait training after the first day; however, during the cued gait phase, gait speed improved, from 0.87 m x s(-1) to 1.13 m x s(-1), as step length was increased with visual cues. Improvements in step length (0.68 m) and gait speed (1.08 m x s(-1)) were still evident 1 month following the removal of the cues. Analyses of angle-angle diagrams and phase-plane portraits revealed that training with visual cues increased hip and knee range of motion and engendered more stable motor control of the lower limb. DISCUSSION AND CONCLUSION: In contrast to previous studies in which the benefits of visual cueing were relatively short-lived, in this study, 1 month of gait training with visual cues was successful in establishing a lasting improvement in gait speed and step length while increasing the stability of the underlying motor control system.

Aged↗

Single-ventricle palliation for high-risk neonates: the emergence of an alternative hybrid stage I strategy.

BACKGROUND: Survival after stage I palliation for hypoplastic left heart syndrome or related anomalies remains poor in high-risk neonates. We hypothesized that a less invasive hybrid approach would be beneficial in this patient population. METHODS: The hybrid stage I procedure was performed in the catheterization laboratory. Via a median sternotomy, both branch pulmonary arteries were banded, and a ductal stent was delivered via a main pulmonary artery puncture and positioned under fluoroscopic guidance. RESULTS: Between October 2003 and June 2005, 14 high-risk neonates underwent a hybrid stage I procedure. Eleven of 14 had hypoplastic left heart syndrome. Two also underwent peratrial atrial septal stenting, and 5 required percutaneous atrial stenting later. Two neonates with an intact or highly restrictive atrial septum had emergency percutaneous atrial stent placement. Hospital survival was 11 (78.5%) of 14. One patient required extracorporeal membrane oxygenation support for intraoperative cardiac arrest. He underwent cardiac transplantation but died later of sepsis. One patient died of ductal stent embolization, and a third died of progressive cardiac dysfunction. The first 4 patients required pulmonary artery band revisions. There were none after we modified our technique and added branch pulmonary artery angiograms. There were 2 interstage deaths from atrial stent occlusion and from preductal retrograde coarctation. Eight patients underwent stage II procedures, consisting of aortic arch reconstruction, atrial septectomy, and cavopulmonary shunt. Two patients died after stage II. One patient is awaiting stage II. CONCLUSIONS: The hybrid stage I palliation is a valid option in high-risk neonates. As experience is accrued, it may become the preferred alternative. However, in aortic atresia, the development of preductal retrograde coarctation is a significant problem.

Cardiac Surgical Procedures↗

Behavioral assessment of joint attention: a methodological report.

This paper describes a highly structured assessment protocol with objective behavioral measures for joint attention responding and initiation. The assessment was given to 26 children diagnosed with autism spectrum disorders and 21 typically developing children, aged two to four years. Interobserver agreement was high for all behavioral measures. Children with autism had relatively minor deficits in joint attention responding and more severe deficits in joint attention initiation, relative to typically developing children. These results replicate those reported in previous research. The protocol can be used reliably to assess behavior indicative of joint attention responding and initiation in typically developing children and children with autism.

Attention↗

A concerted protocol for the analysis of mineral deposits in biopsied tissue using infrared microanalysis.

The mechanism(s) by which crystals are retained in the kidney resulting in stone disease remains unclear. Intratubular aggregation as well as crystal cell binding, or internalization and translocation, or alternatively nucleation and growth in the interstitial fluid are possible models. Our group is testing the hypothesis that calcium phosphate deposits in kidneys of patients with calcium renal stones arise in unique anatomical regions of the kidney. Furthermore, we believe that their formation is conditioned by specific stone forming pathophysiologies. To test this hypothesis, we performed intra-operative renal papillary biopsies during percutaneous nephrolithotomy of kidneys from 15 idiopathic calcium stone formers as well as kidney tissue from a patient who ingested ethylene glycol, and developed a new protocol to accurately identify the composition of the calcium deposits located in the renal tissue. We developed a new histological approach that incorporated a low-energy (low-E) reflective slide substrate that has similar characteristics to a common microscope slide and infrared absorption microspectroscopy. Infrared absorption microspectroscopy revealed the crystal deposits in the idiopathic calcium oxalate stone formers to be hydroxyapatite in composition with an occasional region of calcium carbonate, while calcium oxalate was the predominant mineral in the kidney of the patient who had ingested ethylene glycol. The results demonstrate that mixed sample types containing tissue and mineralized deposits are easily analyzed while mounted on a low-E slide using the attenuated total internal reflectance (ATR) method. Reflection/absorption (R/A) analysis allows one to quickly survey a tissue section and provides qualitative information about its components. Once interesting sites have been identified by R/A analysis, ATR analysis can then be used to collect the best data possible. ATR analysis provides spectra free from many of the artifacts associated with transmission and R/A analysis, and completes the full picture of the components contained in the crystal deposits and tissue. We present a method of analysis for mineralized materials embedded in kidney tissue that uses readily or easily obtainable materials and instrumentation. The sensitivity of this method allows tissue sections to remain unstained, alleviating the tedious and time-consuming constraints of earlier methods of visual analysis. The present method will save time and training, while simultaneously offering an unbiased analysis of mineralized components that is more accurate and conducive to patient treatments than previous methods.

Biopsy↗

Omega-3 for baby and me: material development for a WIC intervention to increase DHA intake during pregnancy.

OBJECTIVE: The purpose of this project was to develop educational materials for a Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) program intervention in Denver, Colorado. Despite accumulating evidence of the importance of docosahexaenoic acid (DHA) during pregnancy, there has been no attempt to develop a targeted nutrition intervention to improve birth outcomes among high-risk women. The goal of the Omega-3 for Baby and Me intervention, for which these materials were developed, is to increase the consumption of DHA-rich foods to decrease the risk for premature delivery and low-birth weight babies among this population. METHOD: Following collection of data from eight focus groups among the target audience, the principles of the Health Belief Model were used to develop materials to address the needs, barriers, and motivators of this audience. In addition, process evaluation pilot testing was used to evaluate recipes and logos during the material development. RESULTS: Materials developed for this intervention include a logo, 9-month calendar, stickers, shopping lists, recipes, recipe holder, magnetic clip, nylon pouch, and recruitment materials. CONCLUSION: The use of focus groups and pilot testing increased the target audience acceptance of education materials that are being used for the Omega-3 for Baby and Me intervention. Successful outcomes from the Omega-3 for Baby and Me intervention, i.e., decreasing the incidence of preterm birth and low-birth weight, will have implications for supplemental food policies at state and national levels.

Colorado↗

Comparative validation of a bilingual interactive multimedia dietary assessment tool.

OBJECTIVE: To perform comparative validity testing for a bilingual interactive multimedia (IMM) dietary assessment tool that mimics a dietary recall against an interview-administered dietary recall. DESIGN: This was a two-period crossover design study. First, participants were randomly assigned to complete an IMM recall or interview-administered 24-hour recall. The IMM recall generated a nutrient profile that included 20 dietary constituents. The interview-administered recall was analyzed using the Food Intake Analysis System (FIAS) and the Expanded Food and Nutrition Education Program (EFNEP) Evaluating/Reporting System. The effect of substituting standardized portion sizes for reported portion sizes was examined. SUBJECTS/SETTING: Of 80 adult participants, 71 (91%) were female, 45 (56%) had 12th grade or less education, 65 (81%) had an annual income of dollar 15,000 or less, and 21 (26%) completed the IMM recall in Spanish. STATISTICAL ANALYSES PERFORMED: Analysis of variance and unadjusted and energy-adjusted correlations were used. RESULTS: No significant group differences were found for order of administration or demographic characteristics. There was only one significant (P=.025) method effect, whereby vitamin C intake was higher in the IMM recall than the FIAS. The unadjusted correlations between the IMM recalls and interview-administered recalls analyzed using both FIAS and EFNEP Evaluating/Reporting System were generally approximately 0.6. Energy-adjusted correlations were consistently lower. Substituting standardized portion sizes resulted in significant differences for six nutrients and caused all correlations to decrease. CONCLUSIONS: The IMM dietary recall is a valid method for assessing dietary intake within the tested group. The results of comparative validity testing and positive reactions received from participants and nutrition educators indicate that diet assessment using IMM has tremendous potential.

Adolescent↗

Isolation of Mycobacterium tuberculosis mutants defective in the arrest of phagosome maturation.

Mycobacterium tuberculosis resides within the phagocytes of its host. It ensures its continued survival through arresting the normal maturation of its phagosome, which is retained within the early endosomal system of the macrophage. Although individual bacterial components have been shown to modulate phagosome biogenesis, the mechanism(s) active in live, intact bacteria remain elusive. We have developed a genetic screen that facilitates the isolation of mutants defective in arresting the maturation of their phagosomes. Macrophages were incubated with iron-dextran that was chased into lysosomes. The cells were subsequently infected with M. tuberculosis from a library of transposon-mutagenized bacteria. After four rounds of enrichment, the majority of mutants isolated were unable to prevent acidification of their phagosomes and were attenuated for intracellular survival. The genes affected range in function from those with no known homologues to putative transporters and lipid synthesis enzymes. Further characterization of these bacteria is needed. In addition to clarifying the processes active in modulation of phagosome biogenesis by M. tuberculosis, this screen may be applicable to other pathogens that restrict the maturation of their phagosome.

Colloids↗

Mycobacterium tuberculosis resides in nonacidified vacuoles in endocytically competent alveolar macrophages from patients with tuberculosis and HIV infection.

Alveolar macrophages (AM) are the first professional phagocytes encountered by aerosols containing infections in the lungs, and their phagocytic capacity may be affected by these infections or environmental particles. The aim of this study was to evaluate the innate endocytic and phagocytic properties of human AM obtained from patients with pulmonary tuberculosis and to characterize the vacuoles in which Mycobacterium tuberculosis bacilli reside in vivo. AM were obtained by bronchoalveolar lavage from patients with suspected tuberculosis and from asymptomatic volunteers (controls). Clinical case definitions were based on mycobacterial culture of respiratory specimens and HIV serology. To assess phagocytosis, endocytosis, and acidification of the endosomal system, AM were cultured with IgG-coated polystyrene beads, dextran, and a pH-sensitive reporter (3-(2,4-dinitroanilino)-3-amino-N-methyldipropylamine) and were evaluated by light and immunoelectron microscopy. Cells from 89 patients and 10 controls were studied. We found no significant difference between the two groups in the ability of AM either to ingest beads and dextran or to deliver them to acidified lysosomes. In AM from patients with tuberculosis, the bacilli were located in vacuoles that failed to accumulate endocytosed material and were not acidified. We concluded that AM from patients with tuberculosis and HIV infections were competent to endocytose and phagocytose material and to deliver the material to functional, acidified lysosomes. M. tuberculosis residing in these AM arrests the progression of their phagosomes, which fail to fuse with acidified lysosomes. This confirms, for the first time in humans with tuberculosis and HIV, the conclusions from previous animal and in vitro studies.

Adult↗

Cox-2 expression in the oxyphilic cells of the normal, hyperplastic, and adenomatous parathyroid gland.

We investigated cyclooxygenase expression in parathyroid glands from patients with various pathological conditions in order to coordinate levels of immunoreactivity with histology, with preoperative serum levels of calcium, phosphate, and intact parathyroid hormone, and with clinical diagnoses. Surgical specimens were obtained from 38 patients diagnosed with adenoma and primary, secondary, and tertiary hyperplasias. Incidentally removed parathyroids served as controls. After routine histological processing, approximations of total area and area of oncocytic nodules were calculated for each section of gland. Immunohistochemical reactivities for Cox-1, Cox-2, and values for integrated Cox-2 reactivity were quantified and compared with the clinical diagnoses and preoperative serum biochemistry. For the pooled cases, serum phosphate and PTH were directly related to each other, to total glandular area, and to integrated oncocytic area. Serum calcium was inversely related to serum phosphate and PTH levels as well as to total gland size. Within the adenoma group, the pure chief cell adenoma patients were younger and their tumors showed greater proliferative activity than those in the oncocytic adenoma group. For secondary and tertiary hyperplasias, the number of oncocytic nodules was significantly higher than in the adenomas and primary hyperplasias. In our study, the oncocytic cells are the only demonstrable site of Cox activity. It is suggested that the oncocytic cells play a role in prostaglandin metabolism within the parathyroids and may have a role in the regulation of PTH secretion.

Adenoma↗

The efficacy and cost effectiveness of N of 1 studies with diclofenac compared to standard treatment with nonsteroidal antiinflammatory drugs in osteoarthritis.

OBJECTIVE: To determine whether or not N of 1 trials with diclofenac/misoprostol (Arthrotec) are superior and cost-effective compared with standard treatment in osteoarthritis (OA). METHODS: We randomized subjects with OA who were "uncertain that nonsteroidal antiinflammatory drugs (NSAID) were helpful" to 2 different groups. One group received conventional treatment whereby they were told to stop their NSAID and to wait and see what happened. If necessary, treatment with other NSAID and all other usual OA treatment strategies were used. The other group received a series of crossover trials with diclofenac 50 mg and misoprostol 200 micro g twice a day or an identical placebo for 2 weeks each in a random double-blinded manner. Every 4 weeks they chose which treatment they preferred. By 3 months, if there was no clear preference, the N of 1 trials were discontinued. All trial participants were seen monthly for 3 months and at 6 months. All costs (direct and indirect) were collected for both groups. Costs of research-generated visits were not counted in the "conventional treatment" group. RESULTS: Fifty-one subjects were randomized (stratified by most symptomatic OA area): 25 with knee, 7 with hip, and 19 with hand OA. Twenty-four were randomized into the N of 1 group. There were no differences in the baseline and followup variables including age, income, education, past and current NSAID use, global assessment, Health Assessment Questionnaire (HAQ), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Medical Outcome Study Short Form-36 (SF-36) scores. In the N of 1 group, 11 patients preferred diclofenac in total (of whom 7 did only one round, 2 did 2 rounds, and 2 did 3 rounds). None of the N of 1 patients preferred placebo and 11 had no preference (2 dropped out at baseline). At 6 months, 15 of 19 in "conventional therapy" and 17 of 21 in N of 1 were taking NSAID. That is, NSAID appeared to be effective in 81% of N of 1 subjects and 79% of conventionally treated patients, even though subjects were initially uncertain that their NSAID were helpful. The total OA-related costs in Canadian dollars per patient (in 1996) for N of 1 treated patients at 6 months were: 551.66 dollars +/- 154.02 dollars (SD) versus 395.62 dollars +/- 226.87 dollars for controls, excluding 2 research visits for controls (p < 0.009). The HAQ pain and disability, WOMAC scales, and physician global assessments improved more in the N of 1 group (at greater cost), but no between-group differences in efficacy were seen, possibly due to small numbers. CONCLUSION: N of 1 trials were time-consuming in these patients and are more expensive, but with slightly better outcomes. In addition, NSAID seem to be effective in a majority of subjects with OA who have been uncertain of their benefit.

Anti-Inflammatory Agents, Non-Steroidal↗

Who is the nurse?

Explore the source record for details and available documents.

Attitude of Health Personnel↗

Gene discovery in the apicomplexa as revealed by EST sequencing and assembly of a comparative gene database.

Large-scale EST sequencing projects for several important parasites within the phylum Apicomplexa were undertaken for the purpose of gene discovery. Included were several parasites of medical importance (Plasmodium falciparum, Toxoplasma gondii) and others of veterinary importance (Eimeria tenella, Sarcocystis neurona, and Neospora caninum). A total of 55192 ESTs, deposited into dbEST/GenBank, were included in the analyses. The resulting sequences have been clustered into nonredundant gene assemblies and deposited into a relational database that supports a variety of sequence and text searches. This database has been used to compare the gene assemblies using BLAST similarity comparisons to the public protein databases to identify putative genes. Of these new entries, approximately 15%-20% represent putative homologs with a conservative cutoff of p < 10(-9), thus identifying many conserved genes that are likely to share common functions with other well-studied organisms. Gene assemblies were also used to identify strain polymorphisms, examine stage-specific expression, and identify gene families. An interesting class of genes that are confined to members of this phylum and not shared by plants, animals, or fungi, was identified. These genes likely mediate the novel biological features of members of the Apicomplexa and hence offer great potential for biological investigation and as possible therapeutic targets.

Animals↗

Differential adoption of pharmacotherapy recommendations for type 2 diabetes by generalists and specialists.

Newer, multimedication (novel) regimens provide better glycemic control for many type 2 diabetics when sulfonylurea monotherapy (traditional) becomes ineffective. Because better glycemic control is associated with decreased likelihood of complications and lower utilization and cost of care, the authors examined change in prescribing patterns for veterans with type 2 diabetes between FY 97 and 99. They classified medication regimens as traditional and novel based on the combination of diabetes medications patients received at the end of each year. Multivariate logistic regression analyses controlling for disease severity indicated that patients were more likely to receive novel regimens over time, but those seen only in primary care were less likely to receive novel regimens than those previously seen by a specialist. Geographic differences and differences in how recommendations were implemented by generalists and specialists suggest that diffusion of innovations theory may help explain variations in practice and guide interventions designed to translate research into practice.

Aged↗

MCID/Low Disease Activity State Workshop: low disease activity state in rheumatoid arthritis.

The MCID (minimal clinically important difference) module of OMERACT 5 developed a research agenda that led to the conclusion that a state of low disease activity for rheumatoid arthritis (RA) would need to be defined. To develop such a definition the various concepts and terminologies, the process for developing an operational definition, and the availability and design of longitudinal datasets for validation needed to be considered. This article describes the process of the MCID/Low Disease Activity State Workshop at OMERACT 6 to develop such a definition.

Arthritis, Rheumatoid↗

MCID/Low Disease Activity State Workshop: summary, recommendations, and research agenda.

The OMERACT 6 Minimal Clinically Important Difference/Low Disease Activity Workshop was organized with the aim of meeting the many challenges that exist in determining a low disease activity in rheumatoid arthritis (RA). This article presents an overview of that workshop, including results of the voting, a summary of associated discussions, recommendations, and a proposed research agenda.

Arthritis, Rheumatoid↗