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Biomedical subjects

S Schwartz

Publications and source records attributed to S Schwartz.

At least 55 records · Page 3Linked to original sources

Modulation of visual perception by eye gaze direction in patients with spatial neglect and extinction.

Parietal neurons have retinotopic receptive fields whose response is modulated by eye gaze signals. We examined the role of eye position and eye movement direction on visual extinction in three patients with parietal damage and left neglect, characterized by impaired perception of contralesional field stimuli despite intact visual cortex. Patients tracked a horizontally moving fixation point, while discriminating fine changes at the fixated point and detecting more salient targets flashed on either side of fixation. Eye position modulated extinction, with worse detection of left field targets during eccentric fixation towards the left. Direction of eye movement also modulated extinction, with worse detection of left targets during rightward scanning. These results demonstrate that extinction in contralesional field is influenced by extra-retinal factors related to eye position and eye movements, consistent with a convergence of these signals in parietal cortex.

Aged↗

A 13-year-old boy with cognitive impairment, retinoblastoma, and Wilson disease.

A developmentally delayed child manifested retinoblastoma at age 4 years and Wilson disease at age 11, a previously unreported association. Cytogenetic and molecular analysis showed an interstitial deletion in the long arm of the paternally derived homologue of chromosome 13 (13q14.2-13q22.2), which encompasses the retinoblastoma and Wilson disease loci. The authors postulate that the co-occurrence of retinoblastoma and Wilson disease was the consequence of an acquired somatic mutation at the retinoblastoma locus and an inherited mutation at the Wilson disease locus of the maternally derived chromosome 13, superimposed on the hemizygosity associated with the paternally derived deletion.

Brain↗

Maternal folate polymorphisms and the etiology of human nondisjunction.

Attempts to identify genetic contributors to human meiotic nondisjunction have met with little, if any, success. Thus, recent reports linking Down syndrome to maternal polymorphisms at either of two folate metabolism enzymes, methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), have generated considerable interest. In the present report, we asked whether variation at MTHFR (677C-->T) or MTRR (66A-->G) might be associated with human trisomies other than trisomy 21. We analyzed maternal polymorphisms at MTHFR and MTRR in 93 cases of sex-chromosome trisomy, 44 cases of trisomy 18, and 158 cases of autosomal trisomies 2, 7, 10, 13, 14, 15, 16, 18, or 22, and compared the distributions of genotypes to those of control populations. We observed a significant increase in the MTHFR polymorphism in mothers of trisomy 18 conceptuses but were unable to identify any other significant associations. Overall, our observations suggest that, at least for the sex chromosomes and for a combined set of autosomal trisomies, polymorphisms in the folate pathway are not a significant contributor to human meiotic nondisjunction.

Case-Control Studies↗

One step at a time: a game plan for success.

Personal success is more likely to occur if individuals establish a concise action plan for achieving their goals. The action plan needs to be in writing, and it should include specific goals, success values, the tasks required to reach the goals, and the intended dates of completion of each task and goal. Goal setting can be accomplished through mental visualization of the goal. A method for creating an action plan is presented in this article.

Goals↗

Beware and be aware: capture of spatial attention by fear-related stimuli in neglect.

Stimuli with threat significance may be privileged in summoning attention, allowing fast detection even outside the field of attention. We studied patients with unilateral neglect and visual extinction, who usually remain unaware of contralesional stimuli presented together with concurrent ipsilesional stimuli, to learn whether emotional stimuli might differentially be affected by contralesional extinction. Pictures of spiders or flowers with similar features were presented in right, left, or both fields. On bilateral trials, the patients detected emotional stimuli (spiders) on the left side much more often than neutral pictures (flowers). While mechanisms of spatial attention are impaired after parietal damage in neglect patients, intact visual pathways to the ventral temporal lobe and amygdala might still mediate distinct mechanisms of emotional attention.

Amygdala↗

[Protein-calorie malnutrition and lymphocytopenia as predictors of hospital infection in the elderly].

BACKGROUND: Clinical and epidemiological studies have established that malnutritionis a risk factor for infection in patients being submitted to surgery. To date no study has been carried out to establish the association between the nutritional condition and the incidence of hospital-acquired infections in patients in the medical area. We study the incidence of hospital-acquired infections in the elderly in an attempt to determine the rate of this infection and its association with protein-calorie malnutrition. Another aim of this study has been to determine the predictive value of the parameters used to evaluate the patient's state of nutrition and immunity. PATIENTS AND METHOD: We included 240 patients over 64 years old, 118 males and 122 females, admitted to the medical area of a general hospital. The nutritional and immunity condition of the patients was evaluated through determinations of weight, height, body mass index, hypoalbuminemia and total lymphocyte count. The psichophisical degree of dependence was evaluated through of Norton scale. The details on the hospital infections came from a clinical and microbiological follow-up of patients, in accordance with the criteria of the Centers for Disease Control of Atlanta. RESULTS: The frequency of protein-calorie malnutrition was 12.5% and the accumulated incidence of hospital-acquired infections was 19.6%. Functional incapacity of the elderly prior to hospitalization (odds ratio,4.70; 95% CI: 1.1-19.0) as well as the presence of certain extrinsicrisk factors (odds ratio, 2.35; 95% CI: 1.1-5.1) were, in addition to hypoalbuminemia (odds ratio, 3.60; 95% CI: 1.3-10.2) and lymphocytopenia(odds ratio, 2.67; 95% CI: 1.3-5.7), the independent variables that showed the most significant association with the incidence of hospital-acquired infections. CONCLUSIONS: The nutritional parameters associated with the immune system determinedgreater risk of hospital-acquired infections among elderly patients admitted to the medical area of a hospital. The initial evaluation of elderly patients hospitalitzed in accordance whit the psychophysical degree of dependence based on the Norton scale is useful to evaluate those patients who were at greater risk for hospital infections.

Aged↗

Comparative analysis of the gene-dense ACHE/TFR2 region on human chromosome 7q22 with the orthologous region on mouse chromosome 5.

Chromosome 7q22 has been the focus of many cytogenetic and molecular studies aimed at delineating regions commonly deleted in myeloid leukemias and myelodysplastic syndromes. We have compared a gene-dense, GC-rich sub-region of 7q22 with the orthologous region on mouse chromosome 5. A physical map of 640 kb of genomic DNA from mouse chromosome 5 was derived from a series of overlapping bacterial artificial chromosomes. A 296 kb segment from the physical map, spanning ACHE: to Tfr2, was compared with 267 kb of human sequence. We identified a conserved linkage of 12 genes including an open reading frame flanked by ACHE: and Asr2, a novel cation-chloride cotransporter interacting protein Cip1, Ephb4, Zan and Perq1. While some of these genes have been previously described, in each case we present new data derived from our comparative sequence analysis. Adjacent unfinished sequence data from the mouse contains an orthologous block of 10 additional genes including three novel cDNA sequences that we subsequently mapped to human 7q22. Methods for displaying comparative genomic information, including unfinished sequence data, are becoming increasingly important. We supplement our printed comparative analysis with a new, Web-based program called Laj (local alignments with java). Laj provides interactive access to archived pairwise sequence alignments via the WWW. It displays synchronized views of a dot-plot, a percent identity plot, a nucleotide-level local alignment and a variety of relevant annotations. Our mouse-human comparison can be viewed at http://web.uvic.ca/~bioweb/laj.html. Laj is available at http://bio.cse.psu.edu/, along with online documentation and additional examples of annotated genomic regions.

Acetylcholinesterase↗

Autosomal dominant limb-girdle muscular dystrophy: a large kindred with evidence for anticipation.

BACKGROUND: Fourteen genetically distinct forms of limb-girdle muscular dystrophy (LGMD) have been identified, including five types of autosomal dominant LGMD (AD-LGMD). OBJECTIVE: To describe clinical, histologic, and genetic features of a large Spanish kindred with LGMD and apparent autosomal dominant inheritance spanning five generations. METHOD: The authors examined 61 members of the family; muscle biopsies were performed on five patients. Linkage analysis assessed chromosomal loci associated with other forms of AD-LGMD. RESULTS: A total of 32 individuals had weakness of the pelvic and shoulder girdles. Severity appeared to worsen in successive generations. Muscle biopsy findings were nonspecific and compatible with MD. Linkage analysis to chromosomes 5q31, 1q11-q21, 3p25, 6q23, and 7q demonstrated that this disease is not allelic to LGMD forms 1A, 1B, 1C, 1D, and 1E. CONCLUSIONS: This family has a genetically distinct form of AD-LGMD. The authors are currently performing a genome-wide scan to identify the disease locus.

Adolescent↗

Emotional facial expressions capture attention.

OBJECTIVE: To determine whether the emotional significance of stimuli can influence spatial attention. BACKGROUND: Motivational and emotional factors may affect attention toward stimuli. However, this has never been examined in brain-damaged patients who present with unilateral inattention due to left spatial neglect. METHODS: The authors studied three patients with chronic left neglect and visual extinction after right parietal stroke. Shapes or faces with neutral, happy, or angry expressions were briefly presented in the right, left, or both visual fields. On unilateral trials, the patients detected all stimuli equally on both sides. On bilateral trials, they extinguished faces in the contralesional field much less often than shapes, and faces with happy or angry facial expressions much less than faces with a neutral expression. CONCLUSION: Facial features and emotional expressions can be analyzed despite lying on the unattended side, and may influence the spatial distribution of attention. These findings support the view that attention is controlled by neural mechanisms involving not only frontoparietal areas but also limbic components in cingulate cortex and amygdala, which may interact with ventral visual areas in the temporal lobe to detect affective value and prioritize attention to salient stimuli.

Aged↗

Quality-of-life outcomes in the evaluation of head and neck cancer treatments.

OBJECTIVES: To review the published literature to evaluate the design, use of terminology, and interpretation of results in studies using quality-of-life (QOL) instruments to measure differences between head and neck cancer treatments at a point in time or to report changes over time in one or more treatment groups. DATA SOURCE: MEDLINE search for subject headings "head and neck neoplasms" (as a main topic) and "quality of life" or "health status" restricted to English-language sources and a 10-year period from 1989 to 1999. STUDY SELECTION: Four hundred forty-five abstracts were reviewed to find articles using an instrument to compare head and neck cancer therapy groups with a QOL outcome (13.7% included). DATA EXTRACTION: Two readers reviewed each article to determine how terminology was used, if a scientific study design was used, and if differences or changes in scores were clinically interpreted. RESULTS: Sixty-one articles were reviewed. Forty different instruments were used. Terminology was used inconsistently in 21 (34.4%) of the 61 articles. A scientific study design was used in only 11 (18.0%) of the 61 articles (P<.001). A clinical interpretation of results was given in 16 (26.2%) of the 61 articles (P<.001). CONCLUSIONS: While QOL outcomes show promise for assisting with treatment decisions in head and neck cancer therapy, few studies using instruments to measure QOL outcomes are hypothesis driven and clinical interpretations of results are not commonly provided. We recommend that future studies identify the construct to be measured, specify comparator groups and hypotheses a priori, and provide clinical interpretations of results.

Head and Neck Neoplasms↗

Intranasal absorption of sumatriptan and naratriptan: no evidence of local transfer from the nasal cavities to the brain arterial blood in male rats.

Nasal administration to rats of small molecules (tritiated water, tyrosine, and propanol) results in a higher concentration in the brain arterial blood than in other arteries. The preferential distribution is based on a counter current transfer, which takes place between nasal vein blood and brain arterial blood in the cavernous sinus-carotid artery complex. This model was used to investigate whether the antimigraine 5HT(1B/1D) receptor agonists sumatriptan and naratriptan may also be transferred by the system. The ratio of 'head':'heart' plasma concentrations obtained from two carotid catheters after intranasal administration was not different from 1.00 for either compound, and thus, there was no experimental evidence of a preferential local transfer of drug from the nose to the carotid artery circulation. However, plasma concentrations increased from the first minute after intranasal dosing suggesting that sumatriptan and naratriptan are absorbed into the general systemic circulation from the nasal cavity in rats in a first-order fashion with no lag time. This is consistent with the clinical onset of efficacy of sumatriptan after an intranasal dose which occurs as early as 15 min post dose.

Absorption↗

Feeding skills and growth after one year of intraoral appliance therapy in moderately dysphagic children with cerebral palsy.

We determined changes in functional feeding skills and growth after one year of intraoral appliance therapy in dysphagic children. Twenty children, 4.2-13.1 years of age (average 8.3 +/- 0.9 years), participated in this study. Children wore the appliance daily. Phase I of treatment (6 months) aimed primarily at stabilizing the mandible and phase II aimed at facilitating ingestive skills. A control period of 6 months preceded treatment. Functional feeding skills improved significantly during phase I beyond changes seen during the control period. Further significant improvement occurred in chewing during phase II. All children significantly gained weight (kg) during the control period, as well as during the two treatment phases. This weight gain was sufficient for children to maintain their growth trajectory. There was also significant growth in height (cm). This growth spurt was characterized by marginal catch-up. Jaw stabilization was a major contributor to the significant improvement in functional feeding skills. Weight gain cannot be attributed to intervention because it occurred during the control period and was the same in magnitude through both treatment phases. However, it permitted a period of growth in stature which previously had been described only after tube feeding.

Activator Appliances↗

Providing toxicokinetic support for reproductive toxicology studies in pharmaceutical development.

A package of toxicokinetic and disposition studies is generally conducted in support of reproductive toxicology studies in the development of new drugs. The content of the package often varies between companies and sometimes either insufficient data or inappropriate/over-interpreted data are presented. This paper was written to aid investigators in the design of toxicokinetic and disposition studies in support of reproductive toxicology. It offers: (1) an overview on the regulatory guidelines for toxicokinetics, (2) methods for the derivation of toxicokinetic parameters, (3) suggestions on general toxicokinetic study design, (4) suggestions on the specific design of toxicokinetic support for reproductive toxicology studies, and (5) an overview of species differences in placental transfer and the applicability (or otherwise) of transfer studies in drug development. Toxicokinetic and drug disposition studies should be carefully designed in order to gather relevant information, and consideration should be given to the usefulness of any data before embarking on a series of supporting or routine experiments.

Animals↗

Early imaging of integration response to polypropylene mesh in abdominal wall by environmental scanning electron microscopy: comparison of two placement techniques and correlation with tensiometric studies.

The repair of incisional hernias has taken advantage of the strength provided by prosthetic mesh grafts, but the best position for inserting the materials has not been conclusively established. Environmental scanning electron microscopy (ESEM) provides imaging of biologic samples with minimal manipulation. We used ESEM for early imaging of the integration response to polypropylene meshes placed in two anatomic positions in the abdominal wall and correlated results with tensiometric studies. Two macroporous polypropylene prostheses were implanted in a rat model--one on the abdominal aponeurotic layer and one on the peritoneal surface--without creating a wall defect. Studies were performed over implantation intervals of 7, 15, and 30 days in strips obtained from the polypropylene fiber-receptor repair tissue interface. Microscopic appearance, tensile strength, percent elongation, and stiffness were evaluated. Meshes implanted on the abdominal aponeurotic layer showed better early tissue incorporation (higher collagen deposition, capillary density, cell accumulation) and increased tensile strength, reflecting tighter anchorage to the abdominal wall. The percent elongation increased from day 7 to day 30 after implantation, mainly in the deep stratum. The ESEM images correlated well with biomechanical results, indicating the potential of this technique as a powerful, effective tool for use in wound-healing studies.

Abdominal Muscles↗

Cytogenetic analysis and construction of a BAC contig across a common neocentromeric region from 9p.

Over 40 cases of neocentric marker chromosomes, without detectable alpha-satellite DNA, have been reported. Although these have originated from many different chromosomes, a few of these chromosomes have been involved in multiple cases of marker formation. In this study, two different markers originating from the short arm of chromosome 9 were analyzed, identifying a common neocentromeric region. A bacterial artificial chromosome (BAC) contig extending over more than 900 kb has been assembled across this neocentromeric region. Fluorescent in situ hybridization and immunofluorescence assays (CENP-C and CENP-E) have localized the neocentromere to a 500 kb region. Preliminary analysis of DNA sequences in this neocentromere revealed a highly AT-rich region, which also has an increase in the level of retroviral elements compared with the average levels in the genome.

Animals↗

Impact of oral appliance therapy: are oral skills and growth maintained one year after termination of therapy?

To determine the impact of intraoral appliance (ISMAR) therapy on functional feeding skills and growth, children with cerebral palsy and moderate dysphagia were followed a full year after termination of one year of ISMAR therapy. Seventeen children, 6.6-15.4 years old (mean age = 10.2 +/- 3.0 years), were divided into two groups: group A (n = 9) continued to wear the appliance and group B (n = 8) no longer wore the appliance. Generalized estimating equations (GEE) were used to test differences between the two groups over time while accounting for the dependence for the repeated within-subject measurements. No significant differences were found in the 7 domains of functional feeding. Significant time x group interactions for weight (kg and z-score 0.01 < p < 0.05) were found. However, post hoc analyses showed that there were no significant differences in weight changes between the two groups at either 18 or 24 months of followup. These results suggest that during a one-year period of followup, maturation was equally effective as ISMAR therapy.

Adolescent↗

Intracellular hepatitis C virus RNA-dependent RNA polymerase activity.

Studies of intracellular hepatitis C virus (HCV) RNA-dependent RNA polymerase activity (RdRp activity) have been limited by the poor replicative capacity of HCV in cell culture. We have developed a method that allows for the measurement of HCV specific RdRp activity in eukaryotic cells. This method is based on the transient expression of the HCV polymerase and its templates under the control of the T7 promoter in the presence of an infection with recombinant vaccinia virus (vTF7-3) expressing the bacteriophage T7 DNA-dependent RNA polymerase. Both negative-strand and positive-strand RNA synthesis were characterised, and the role of the other HCV non-structural proteins for polymerase activity was assessed. With this assay we were able to show that: a) Intracellular HCV RdRp activity is not restricted to, but is higher for templates containing HCV specific sequences, b) The HCV polymerase is active within the polyprotein precursor, c) Cleavage of NS5b from the polyprotein precursor does not determine template specificity, and d) HCV RdRp activity is higher in the presence of the other HCV non-structural proteins and lower within a protease-deficient polyprotein precursor. This method allows the measurement of intracellular HCV polymerase activity and may be used to test substances against the HCV polymerase in search of potential drugs for anti-HCV therapy.

HeLa Cells↗

Massive suprachoroidal hemorrhage during pars plana vitrectomy associated with Valsalva maneuver.

PURPOSE: To report the intraoperative occurrence of massive intraocular suprachoroidal hemorrhage associated with Valsalva maneuver. METHODS: Retrospective, multicenter study of patients who developed massive choroidal hemorrhage associated with Valsalva maneuver during vitrectomy. RESULTS: Massive intraoperative suprachoroidal hemorrhage in seven patients (seven eyes) involved three men and four women with a median age of 52 years (range, 26 to 82 years). General anesthesia was used in six of seven cases. Coughing or "bucking" on the endotracheal tube during general anesthesia or severe coughing during the one vitrectomy performed under local anesthesia was associated with massive suprachoroidal hemorrhage. In five of seven eyes, this occurred near the end of surgery, after air-fluid exchange but before sclerotomy closure. Scleral plugs were immediately placed, and sclerotomy closure was performed exigently. Immediate posterior sclerotomy was performed on five of seven eyes; an additional patient underwent posterior sclerotomy postoperatively. After median follow-up of 18 months (range, 3 to 36 months), final visual acuity was no light perception in four eyes, light perception in one eye, 20/250 in one eye, and 20/20 in one eye. Four eyes became phthisical. CONCLUSIONS: Valsalva maneuver during pars plana vitrectomy may result in massive suprachoroidal hemorrhage with disastrous visual consequences. Precautionary measures to prevent coughing or "bucking" on the endotracheal tube during general anesthesia, or a prolonged episode of coughing during local anesthesia, may prevent this potentially devastating complication.

Adult↗