Can endogenous stem cells be stimulated to repair the degenerating brain?
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Animals↗
Biomedical subjects
W Phillips
Publications and source records attributed to W Phillips.
Iatrogenic ulnar neuropathies post-pinning of displaced supracondylar humerus fractures in children.
A retrospective review of 141 displaced supracondylar fractures in children at the Bustamante Children's Hospital and the University Hospital of the West Indies from 1994 to 1999 revealed ten ulnar nerve palsies. Of the 141 supracondylar fractures, 27 were treated with open reduction and internal fixation, while 114 had closed reduction and percutaneous pinning. All fractures were fixed with crossed Kirschner wires. Of the ten cases, the ulnar nerve was explored in two cases; the medial pin was removed in two cases, while the other six cases were observed. Follow-up ranged from three to 18 months. Full nerve recovery occurred in all cases except one in which there was partial return of function. Recommendations are made regarding the management of these injuries.
Bone Wires↗
Heart failure and apoptosis: electrophoretic methods support data from micro- and macro-arrays. A critical review of genomics and proteomics.
The multiple causes and multiple consequences of mammalian heart failure make it an attractive proposition for analysis using gene array technology, especially where the failure is idiopathic in nature. However, gene arrays also hold potential artefacts, particularly when gene expression levels are low, and where changes in expression levels are modest. Also, at present, the number of genes available on arrays is not large enough to prevent potential sampling deficiencies. Thus, it may not be wise to place too much reliance on quantitative interpretations of gene array data. Also, recently doubts were raised about the qualitative reliability of array genes. Electrophoretic methods are slow, cumbersome and complex but they can provide confirmation that the trends and numbers arising from the new gene arrays are reliable. In this overview, we compare gene array data with data from protein activity assays such as zymograms, Western blots, two-dimensional electrophoresis, and immunohistochemistry. Similar or complementary data from the same heart tissues analyzed by either microarrays or macroarrays can be reassuring to those interested in reliable molecular analyses of normal and failing hearts. Similar principles will apply to other tissues and cells.
Animals↗
Receptor-mediated targeting of spray-dried lipid particles coformulated with immunoglobulin and loaded with a prototype vaccine.
PURPOSE: Spray-dried lipid-based microparticles (SDLM) serve as a platform for delivery of a wide variety of compounds including peptides, proteins, and vaccines to the respiratory mucosa. In the present study, we assessed the impact of IgG-mediated targeting to phagocytic cells of inactivated influenza virus formulated in SDLM, on subsequent immune responses. METHODS: SDLM were produced containing inactivated influenza virus strain A/WSN/32/H1N1 (WSN), with or without IgG. Using phagocytic antigen presenting cells (APC) and a T cell hybridoma (TcH) line specific for a dominant influenza virus epitope, we compared the in vitro responses elicited by ligand-formulated (SDLM-IgG-WSN) and non-ligand particles (SDLM-WSN). The effect of including the IgG ligand in the formulation was further characterized by measuring the immune responses of rodents vaccinated with SDLM. RESULTS: SDLM-IgG-WSN were internalized in an Fc receptor (FcR)-dependent manner by phagocytic APC that were then able to effectively present a dominant, class II-restricted epitope to specific T cells. While SDLM-WSN elicited a lower response than administration of plain inactivated virus in saline, the level of the T cell response was restored both in vitro and in vivo by incorporating the APC FcR ligand, IgG, in the SDLM. CONCLUSIONS: Incorporation of FcR ligand (IgG) in SDLM restored the limited ability of formulated virus to elicit T-cell immunity, by receptor-mediated targeting to phagocytes.
Administration, Inhalation↗
The effectiveness of the levonorgestrel-releasing intrauterine system in menorrhagia: a systematic review.
OBJECTIVE: To determine whether the levonorgestrel-releasing intrauterine device (LNG-IUS), licensed at present for contraceptive use, may reduce menstrual blood loss with few side effects. If effective, surgery could be avoided with consequent resource savings. METHODS: A systematic review addressing the effectiveness and cost effectiveness of the LNG-IUS for menorrhagia was undertaken. RESULTS: Five controlled trials and five case series were found which measured menstrual blood loss. Nine studies recorded statistically significant average menstrual blood loss reductions with LNG-IUS (range 74%-97%). Another showed reduction in menstrual disturbance score. The LNG-IUS was more effective than tranexamic acid, but slightly less effective than endometrial resection at reducing menstrual blood loss. In one study, 64% of women cancelled surgery at six months, compared with 14% of control group women. In another, 82% were taken off surgical waiting lists at one year. No cost effectiveness studies were found. DISCUSSION: Small studies of moderate quality indicate the LNG-IUS is an effective treatment for menorrhagia. Costs may be less than for tranexamic acid in primary and secondary care. Although its use may reduce surgical waiting lists, cost effectiveness assessment requires longer follow up. CONCLUSION: Effectiveness and cost effectiveness relative to other treatments and the effect on surgical waiting lists can only be established in larger trials measuring patient-centred outcomes in women with menorrhagia.
Adult↗
9:15-9:30. Use of a Spherical 3-D Blob Analysis Program as a Method of Determination of Standardized Uptake Value (SUV) for Following Tumor Response to Chemotherapeutic Agents (CTA).
Malignant tumors exhibit increased glucose metabolism which can be quantitated by SUV. SUV is criticized for its variability resulting from many factors including the method of drawing region of interest (ROI) over the tumor. The most common method manually draws or places ROI on various slices displaying highest FDG activity. This time consuming method is associated with significant individual variation. We describe a more reproducible, efficient spherical 3-D blob analysis method of SUV and tumor volume (TV) determination to evaluate CTA response. The spherical 3-D Blob analysis program is a completely automated method with data processing performed using IDL (RS Inc., Colorado). A threshold value is set for the ROI; all voxels above threshold are grouped by connectivity. Grouped voxels, called "blobs", are displayed and statistics are calculated for each group. The threshold set for blob extraction and SUV determination is usually three times above background and is constant on repeat scans. Eight patients with metastatic carcinoma underwent PET/CT/MRI prior to and one week after chemotherapy. Three patients also had scans at one month. Maximum and average SUV's and TV were determined and appeared to be very reproducible when there was no clinical response or change on CT/MR. In these patients, repeat SUV's and volumes of the lesions (n = 38) varied by less than 20% of baseline. An increase/decrease in maximum SUV or TV correlated with a similar change in lesion size on CT/MR. The average SUV did not change. The spherical 3-D blob analysis program appears to be a reliable, efficient method of determining maximum SUV and volumetric measurements for following tumor response to CTA.
Journal Article↗
The Awkward Moments Test: a naturalistic measure of social understanding in autism.
Details are given of a new advanced theory of mind task, developed to approximate the demands of real-life mentalizing in able individuals with autism. Excerpts of films showing characters in social situations were presented, with participants required to answer questions on characters' mental states and on control, nonsocial questions. When compared with control participants, adults with high-functioning autism and Asperger syndrome were most impaired in their ability to answer the questions requiring mind-reading ability. Although the present findings have implications for task modification, such naturalistic, dynamic stimuli are held to offer an important means of studying subtle difficulties in mentalistic understanding.
Adult↗
Linkage disequilibria and the site frequency spectra in the su(s) and su(w(a)) regions of the Drosophila melanogaster X chromosome.
Over the last decade, surveys of DNA sequence variation in natural populations of several Drosophila species and other taxa have established that polymorphism is reduced in genomic regions characterized by low rates of crossing over per physical length. Parallel studies have also established that divergence between species is not reduced in these same genomic regions, thus eliminating explanations that rely on a correlation between the rates of mutation and crossing over. Several theoretical models (directional hitchhiking, background selection, and random environment) have been proposed as population genetic explanations. In this study samples from an African population (n = 50) and a European population (n = 51) were surveyed at the su(s) (1955 bp) and su(w(a)) (3213 bp) loci for DNA sequence polymorphism, utilizing a stratified SSCP/DNA sequencing protocol. These loci are located near the telomere of the X chromosome, in a region of reduced crossing over per physical length, and exhibit a significant reduction in DNA sequence polymorphism. Unlike most previously surveyed, these loci reveal substantial skews toward rare site frequencies, consistent with the predictions of directional hitchhiking and random environment models and inconsistent with the general predictions of the background selection model (or neutral theory). No evidence for excess geographic differentiation at these loci is observed. Although linkage disequilibrium is observed between closely linked sites within these loci, many recombination events in the genealogy of the sampled alleles can be inferred and the genomic scale of linkage disequilibrium, measured in base pairs between sites, is the same as that observed for loci in regions of normal crossing over. We conclude that gene conversion must be high in these regions of low crossing over.
Animals↗
Comparative effects of two physical activity programs on measured and perceived physical functioning and other health-related quality of life outcomes in older adults.
BACKGROUND: Although inactivity is an important contributor to impaired functioning and disability with age, little is known concerning how improvements in physical functioning and well-being in older adults vary with the type of physical activity undertaken. METHODS: One hundred three adults age 65 years and older, recruited via population-based methods, were randomized to 12 months of community-based, moderate-intensity endurance and strengthening exercises (Fit & Firm) or stretching and flexibility exercises (Stretch & Flex). A combination of class- and home-based exercise formats was used. Measured and self-rated physical performance along with perceived functioning and well-being were assessed pre- and postintervention. RESULTS: Fit & Firm subjects showed greater 12-month improvements in both measured and self-rated endurance and strength compared to Stretch & Flex subjects. Stretch & Flex subjects reported greater improvements in bodily pain, and Stretch & Flex men evidenced greater improvements in flexibility relative to Fit & Firm subjects. Although overall exercise adherence was high in both exercise conditions (approximately 80%), subjects in both conditions showed better adherence to the home- versus class-based portions of their exercise prescriptions. CONCLUSIONS: Community-based programs focusing on moderate-intensity endurance and strengthening exercises or flexibility exercises can be delivered through a combination of formats that result in improvement in important functional and well-being outcomes. This represents one of the first studies to report significant improvements in an important quality of life outcome-bodily pain-with a regular regimen of stretching and flexibility exercises in a community-based sample of older adults.
Activities of Daily Living↗
Transgenic tomato plants with decreased sucrose synthase are unaltered in starch and sugar accumulation in the fruit.
Sucrose is the photoassimilate transported from the leaves to the fruit of tomato yet the fruit accumulates predominantly glucose and fructose. Hydrolysis of sucrose entering the fruit can be accomplished by invertase or sucrose synthase. Early in tomato fruit development there is a transient increase in sucrose synthase activity and starch which is correlated with fruit growth and sink strength suggesting a regulatory role for sucrose synthase in sugar import. Using an antisense sucrose synthase cDNA under the control of a fruit-specific promoter we show that sucrose synthase activity can be reduced by up to 99% in young fruit without affecting starch or sugar accumulation. This result calls into question the importance of sucrose synthase in regulating sink strength in tomato fruit.
Cell Wall↗
Analysis of the detective quantum efficiency of a developmental detector for digital mammography.
We are developing a modular detector for applications in full field digital mammography and for diagnostic breast imaging. The detector is based on a design that has been refined over the past decade for applications in x-ray crystallography [Kalata et al., Proc. SPIE 1345, 270-279 (1990); Phillips et al. ibid. 2009, 133-138 (1993), Phillips et al., Nucl. Instrum. Methods Phys. Rev. A 334, 621-630 (1993)]. The full field mammographic detector, currently undergoing clinical evaluation, is formed from a 19 cm x 28 cm phosphor screen, read out by a 2 x 3 array of butted charge-coupled device (CCD) modules. Each 2k x 2k CCD is optically coupled to the phosphor via a fiber optic taper with dimensions of 9.4 cm x 9.4cm at the phosphor. This paper describes the imaging performance of a two-module prototype, built using a similar design. In this paper we use cascaded linear systems analysis to develop a model for calculating the spatial frequency dependent noise power spectrum (NPS) and detective quantum efficiency (DQE) of the detector using the measured modulation transfer function (MTF). We compare results of the calculation with the measured NPS and DQE of the prototype. Calculated and measured DQEs are compared over a range of clinically relevant x-ray exposures and kVps. We find that for x-ray photon energies between 10 and 28 keV, the detector gain ranges between 2.5 and 3.7 CCD electrons per incident x-ray, or approximately 5-8 electrons per absorbed x ray. Using a Mo/Mo beam and acrylic phantom, over a detector entrance exposure range of approximately 10 to 80 mR, the volume under the measured 2-d NPS of the prototype detector is proportional to the x-ray exposure, indicating quantum limited performance. Substantial agreement between the calculated and measured values was obtained for the frequency and exposure dependent NPS and DQE over a range of tube voltage from 25 to 30 kVp.
Algorithms↗
Picosecond photoluminescence decay of Si-doped chemical-vapor-deposited diamond films.
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Journal Article↗
Human CD34+ hematopoietic progenitors have low, cytokine-unresponsive O6-alkylguanine-DNA alkyltransferase and are sensitive to O6-benzylguanine plus BCNU.
Human bone marrow (BM) cells contain low levels of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase, which may explain their susceptibility to nitrosourea-induced cytotoxicity and the development of secondary leukemia after nitrosourea treatment. Isolated CD34+ myeloid progenitors were also found to have low levels of alkyltransferase activity. The level of alkyltransferase in CD34+ cells or in mononuclear BM cells did not increase after incubation with granulocyte-macrophage colony-stimulating factor, interleukin-3, stem cell factor, the combination, or 5637 conditioned medium. BCNU sensitivity remained unchanged as well. In addition, O6-benzylguanine depleted alkyltransferase activity in BM cells at concentrations as low as 1.5 mumol/L after a 1-hour exposure. O6-benzylguanine pretreatment markedly sensitized hematopoietic progenitor colony-forming cells to BCNU, resulting in a reduction in the dose of drug (termed the dose-modification factor) required to inhibit 50% of the colony formation (IC50) of threefold to fivefold. Since, unlike many other cell types, proliferating early (CD34+) hematopoietic precursors do not induce alkyltransferase, myelosuppression may be the dose-limiting toxicity of the combination of O6-benzylguanine plus BCNU in clinical trials.
Adult↗
Human colour discrimination based on a non-parvocellular pathway.
BACKGROUND: Traditionally, colour information is assumed to be carried by neural channels in the parvocellular pathway and to be encoded in an opponent manner, while other, non-parvocellular, spectrally non-opponent channels are thought to play no part in colour vision. But is the parvocellular pathway the only way that colours can be discriminated in human vision? We studied two patients with cerebral achromatopsia, who lack conscious colour perception but are nevertheless able to make use of colour information. In particular, we investigated whether, in these patients, colour discrimination is mediated by the parvocellular pathway. RESULTS: The achromatopsic patients carried out a forced-choice colour- and luminance-discrimination task, and showed clear evidence of unconscious colour processing, consistent with previous studies. We added different types of luminance noise to see when this unconscious colour information could be masked. The results of the colour-discrimination-with-noise and the brightness-non-additivity experiments showed a double-dissociation between patients. This indicates that, in one patient, unconscious colour discrimination may be subserved by a spectrally non-opponent mechanism, which does not have the characteristics of the parvocellular pathway and which is responsive to fast flicker. Spectral sensitivity, contrast sensitivity and motion perception experiments confirmed that this patient lacks a working opponent parvocellular system. The second achromatopsic patient showed evidence of a residual parvocellular system. CONCLUSIONS: Our results show that chromatic discrimination need not be mediated by neural mechanisms, the parvocellular system in particular, normally assumed to subserve conscious colour perception. Such discrimination may be mediated by a neural subsystem which responds to fast flicker, is spectrally non-opponent, and supports normal motion perception.
Aged↗
Behavioral and cognitive effects of methylxanthines. A meta-analysis of theophylline and caffeine.
BACKGROUND: Theophylline has been extensively studied as a treatment of asthma. However, some studies have suggested that theophylline may precipitate adverse behavioral and cognitive effects on children. Other reports have evaluated the effects of caffeine, another commonly used methylxanthine, as a treatment of attention-deficit hyperactivity disorder. OBJECTIVE: To present a meta-analysis of research on the behavioral and cognitive effects of methylxanthines in children. METHODS: The meta-analyses were conducted on 12 studies of theophylline and nine studies of caffeine that met inclusion criteria. RESULTS: In contrast to popular beliefs and earlier scientific reports, meta-analyses of controlled studies did not indicate that either theophylline or caffeine resulted in significant deleterious effects on cognition or behavior. In fact, there was a small, positive effect on parental report of externalizing behavior for both methylxanthines. CONCLUSIONS: There is little evidence to suggest that methylxanthines have adverse cognitive or behavioral effects on children. Questions remain with regard to the identification and determinants of either responsive or sensitive subgroups, dose-response relationships, and the effects of parent-teacher expectancies on behavioral ratings.
Adolescent↗
Autism: towards an integration of clinical, genetic, neuropsychological, and neurobiological perspectives.
Autism constitutes one of the best validated child psychiatric disorders. Empirical research has succeeded in delineating the key clinical phenomena, in demonstrating strong genetic influences on the underlying liability, and in identifying basic cognitive deficits. A range of neurobiological abnormalities has also been found, although the replicability of specific findings has not been high. An understanding of the causal processes leading to autism, and accounting for the marked variability in its manifestations, requires an integration across these different levels of enquiry. Although this is not yet possible, a partial integration provides a useful strategy for identifying key research questions, the limitations of existing hypotheses, and future research directions that are likely to prove fruitful. The research findings for each research level are critically reviewed in order to consider how to move towards an integration across levels.
Adolescent↗
Strength and muscle mass changes in elderly men following maximal isokinetic training.
The purpose of this study was to determine the effects of a maximal isokinetic training program on strength and muscle mass in a group of untrained men 73 +/- 7.3 (range 68-82) years of age. Testing and training were conducted on an isokinetic dynamometer. Training consisted of one set of six maximal knee flexion and extension movements at 60 deg*s(-1) performed three times per week for 12 weeks. The subjects trained the right leg only, the left leg serving as a within-subject control. Trained leg peak torque increased by 18.1% for knee extension (from 107.2 +/- 42.9 to 126.6 +/- 44.6 Nm; p < 0.05) and by 18.2% for knee flexion (from 85.1 +/- 21.1 to 100.4 + or - 25.5 Nm; p < 0.05). Urinary creatinine levels increased by 24.3% (NS). We conclude that maximal isokinetic training at 60 deg*s(-1) increases strength and a urinary index of muscle mass in a group of aged untrained men.
Aged↗
Frequent use of medical services. Patient reports of intentions to seek care.
OBJECTIVE: To examine differences between frequent and infrequent users in decisions to seek medical care based on symptom type and duration of experience of the symptom. DESIGN: Retrospective study. SETTING: University family practice clinic. PATIENTS: Fifty-eight of 130 patients returned the completed instruments, a response rate of 45%. MAIN OUTCOME MEASURES: The following two instruments were used: the Intentions to Seek Care questionnaire, which measures intention to see a physician, self-treat, or use medications for 11 different symptoms after three time periods--1 day, 3 days, and 1 week of symptom duration--and the SF-36 Health Survey measure. RESULTS: Initial analyses suggested that patients perceive three clusters of symptoms, which we have labeled as serious, mild, and psychological. Scale scores for these groups of symptoms yielded significant reliability and were used in subsequent analyses. Multivariate analysis of variance comparing source of care, symptom duration, and frequent vs infrequent user groups indicated that both user groups are more likely to seek care from physicians for symptoms that are serious. Analysis of mild and psychological symptoms yielded significant three-way interactions, with frequent users more likely than infrequent users to seek care from physicians at a 1-day duration. Such differences disappear by 7 days. Significantly lower scores were obtained on five of the eight SF-36 Health Survey dimensions for the infrequent users. CONCLUSIONS: Frequent users are more likely than infrequent users to report that they would seek care for minor symptoms. Infrequent users tend to self-treat for 3 to 7 days, after which time physician advice is sought. Efforts to teach patients optimal timing of use for different symptoms may be an effective intervention.
Family Practice↗