Search PubMed⌕ Search

Biomedical subjects

A Thompson

Publications and source records attributed to A Thompson.

At least 145 records · Page 8Linked to original sources
PubMed1998

Telemedicine in pediatric transport: a feasibility study.

OBJECTIVE: Investigate the hypothesis that telemedicine, in the form of real-time audiovisual transmission, would permit accurate assessment of illness severity and allow improved triage for transport. METHODS: A prospective study comparing assessments of patients examined conventionally (in person) and remotely by a telemedicine link. Fifteen patients (3 months to 14 years of age) admitted to our emergency department were evaluated as if for transport. Patients were evaluated simultaneously by a physically present pediatric emergency room physician and by a pediatric critical care physician linked to the examining room by a broadband audiovisual link. Each physician completed a patient assessment questionnaire independently. The sensitivity and specificity of the patient assessment by the audiovisually linked physician were calculated. RESULTS: Sensitivity, ie, the ability of the remote, audiovisually connected telemedicine physician to detect abnormal findings, is 87.5%. Specificity, the ability of the remote physician to detect normal findings, is 93%. It is likely that sensitivity would be markedly improved with addition of an electronic stethoscope. CONCLUSION: This study demonstrates that pediatric patients may be assessed accurately with a broadcast-quality real-time audiovisual system. Such a system may have dramatic implications for providing pediatric specialty and subspecialty care in underserved areas.

Adolescent↗
PubMed1998

Stimulation of angiogenesis by FGF-1 delivered through a modified fibrin scaffold.

A few studies have indicated that repeated dosing of acidic fibroblast growth factor (FGF-1) is essential to be effective in modulating the wound-healing response. However, little investigation has been done to determine the effective dosing regimen of FGF-1 or the appropriate carrier vehicle for this growth factor. The main objective of this study was to determine the effective angiogenic stimulatatory dose of FGF-1 delivered through a modified fibrin matrix, using a rabbit ear ulcer model. Specifically, the aim was to test the effects of FGF-1 on the angiogenic, fibroblastic, and epithelial responses in a wound model. Five 6-mm diameter ulcers to the depth of bare cartilage were created on each rabbit ear. Four different combinations (0.8, 8, 80, and 800 micrograms/ml) of the growth factor were examined across two periods of study. Pooled modified fibrin was used to deliver the growth factor. Histomorphometrical quantification was conducted after routine histological processing of the ulcers sites. Data analysis indicated a strong correlation between concentration and the histomorphometric response. In general, the growth factor treatments affected the healing response and exhibited a dose-dependent behavior. The addition of FGF-1 led to an increase in the angiogenic and fibroblastic responses, as well as an increase in the epithelialization rate. The preferred dose of 8 micrograms initiated a high epithelialization rate, fibroblastic, and angiogenic responses, and was the lowest dose required to initiate these responses.

Animals↗
PubMed1998

Properties of adenosine monophosphate deaminase of Candida albicans.

Adenosine monophosphate deaminase (AMPD; EC 3.5.4.6) catalyses the hydrolysis of adenosine monophosphate (AMP) to commensurate amounts of inosine monophosphate (IMP) and ammonia. The production of AMP deaminase in Candida albicans was measured in Lee's medium grown cultures. The highest AMPD activity was observed at 24 h of growth. The enzyme had an optimum pH and temperature at 6-7 and 28 degrees C, respectively. This enzyme was inhibited under iron-limited growth conditions as well as by protease inhibitors. The AMPD of C. albicans showed a moderate increase in activity when cultures were grown in the presence of the divalent cations Mg2+, Ca2+, and Zn2+. Moreover, ADP, ATP, adenine, adenosine, deoxyribose and hypoxanthine increased the enzyme activity. Cultures grown in trypticase soy broth exhibited maximum AMPD activity compared with those grown in Sabouraud dextrose broth or Lee's medium.

AMP Deaminase↗
PubMed1998

Congenital diaphragmatic hernia survival and use of extracorporeal life support at selected level III nurseries with multimodality support.

BACKGROUND: Congenital diaphragmatic hernia (CDH) has been cited to have a mortality rate of 50%. There have been multiple studies at individual institutions demonstrating potential benefits from various strategies including extracorporeal life support (ECLS), delayed repair, and lower levels of ventilator support. There has been no multicenter survey of institutions offering these modalities to describe the current use of ECLS and survival of these infants. In addition, the relationship between the number of patients with CDH managed at an individual institution and outcome has not been evaluated. METHODS: We queried 16 level III neonatal intensive care centers on the use of ECLS and survival of infants with CDH who were treated during 2 consecutive years (1993 to 1995). Data are presented as mean +/- SEM, median, and range. RESULTS: Data were collected on 411 patients. Of these, 71% +/- 8% were outborn and 8% +/- 3% were considered nonviable. Overall survival of CDH infants was 69% +/- 4% (range, 39% to 95%). The survival rate of infants on ECLS was 55% +/- 4%, whereas survival of infants not requiring ECLS was significantly increased at 81% +/- 5% (p = 0.005). The mean rate of ECLS use was 46% +/- 2%. There was no correlation between the number of cases per year at an individual institution and overall survival, ECLS survival, or ECLS use (r = 0.341, 0.305, and 0.287, respectively). There was also no correlation between case volume at an individual institution and ECLS survival (r = 0.271). CONCLUSIONS: The current survival rate and rate of ECLS use in infants with CDH at level III neonatal intensive care units in the United States are 69% +/- 4% and 46% +/- 2%, respectively. There is no correlation between the yearly individual center experience with managing CDH and rate of ECLS use or outcome.

Extracorporeal Circulation↗
PubMed1998

Inhibition of renal 11beta-hydroxysteroid dehydrogenase in vivo by carbenoxolone in the rat and its relationship to sodium excretion.

1. The type 2 isoform of 11beta-hydroxysteroid dehydrogenase, an enzyme which converts cortisol or corticosterone to inactive 11-ketosteroid metabolites, is thought to be responsible for preventing access of endogenous glucocorticoids to mineralocorticoid receptors in the distal nephron; although direct in vivo evidence for this is still lacking. We have examined whether graded inhibition of renal 11beta-hydroxysteroid dehydrogenase activities in vivo results in corresponding changes in urinary electrolyte excretion due to exposure of mineralocorticoid receptors to circulating endogenous glucocorticoids.2. Anaesthetized rats were infused intravenously with vehicle alone or with one of three doses of carbenoxolone: 0.06, 0.6 or 6 mg/h. After measurement of renal electrolyte excretion, the kidneys were snap-frozen in liquid nitrogen and 11beta-hydroxysteroid dehydrogenase activities were measured directly by enzyme assay in the presence of NAD+ or NADP+.3. A dose-dependent inhibition of renal 11beta-hydroxysteroid dehydrogenase activities was observed: the low, intermediate and high doses of carbenoxolone causing approximately 50%, 80% and >90% inhibition respectively. Only with the high dose was an effect on renal function observed (decreased fractional Na+ excretion and urinary Na+/K+ ratio).4. The poor correlation between the extent of inhibition of renal 11beta-hydroxysteroid dehydrogenase and altered urinary Na+ excretion, apparent at the lower doses of carbenoxolone, suggests either that 11beta-hydroxysteroid dehydrogenase has considerable functional reserve, or that it may not be the only mechanism determining mineralocorticoid receptor specificity in the distal nephron.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

The crystal structure of dimeric kinesin and implications for microtubule-dependent motility.

The dimeric form of the kinesin motor and neck domain from rat brain with bound ADP has been solved by X-ray crystallography. The two heads of the dimer are connected via a coiled-coil alpha-helical interaction of their necks. They are broadly similar to one another; differences are most apparent in the head-neck junction and in a moderate reorientation of the neck helices in order to adopt to the coiled-coil conformation. The heads show a rotational symmetry (approximately 120 degrees) about an axis close to that of the coiled-coil. This arrangement is unexpected since it is not compatible with the microtubule lattice. In this arrangement, the two heads of a kinesin dimer could not have equivalent interactions with microtubules.

Adenosine Diphosphate↗
PubMed1997

The 2.35 A crystal structure of the inactivated form of chicken Src: a dynamic molecule with multiple regulatory interactions.

The Src protein tyrosine kinase plays a critical role in a variety of signal transduction pathways. Strict regulation of its activity is necessary for proper signalling. We present here the crystal structure of chicken Src which is phosphorylated at Tyr527 and represents its least active form. Our structure, similar to the recently reported human Hck and Src structures, contains the SH3, SH2 and the kinase domains and the C-terminal regulatory tail but not the N-terminal unique domain. The SH3 domain uses its hydrophobic surface to coordinate the SH2-kinase linker such that residues Gln251 and Leu255 specifically interact with side chains in the beta2-beta3 and the alphaC-beta4 loops of the N-terminal lobe opposite of the kinase active site. This position of the SH3 domain and the coordination of the SH2-kinase linker also optimally places the SH2 domain such that the phosphorylated Tyr527 in the C-terminal tail interacts with the SH2 binding pocket. Analogous to Cdk2 kinase, the position of the Src alphaC-helix in the N-terminal lobe is swung out disrupting the position of the active site residues. Superposition of other protein kinases including human Hck and Src onto chicken Src indicate that the alphaC-helix position is affected by the relative position of the N-terminal lobe with respect to the C-terminal lobe of the kinase and that the presence of the SH3/SH2-kinase linker/N-terminal lobe interactions restricts the kinase lobes and alphaC-helix access to the active conformation. These superpositions also suggest that the highly conserved alphaC-beta4 loop restricts the conformational freedom of the N-terminal lobe by anchoring it to the C-terminal lobe. Finally, based on sequence alignments and conservation of hydrophobic residues in the Src SH2-kinase linker as well as in the alphaC-beta4 and beta2-beta3 loops, we propose that the Src-related kinases, Abl, Btk and Csk, share the same quaternary structure.

Amino Acid Sequence↗
PubMed1997

Recommendations from the National Multiple Sclerosis Society Clinical Outcomes Assessment Task Force.

This article provides recommendations from the National Multiple Sclerosis Society's Clinical Outcomes Assessment Task Force. The Task Force was appointed in 1994 and charged with recommendending improved approaches for clinical outcomes assessment in future controlled clinical trials. The recommendations herein follow extensive deliberation and data analysis during 2.5 years. General principles and desirable measurement attributes were used to assess alternative measurement techniques and clinical scales. On the basis of the analysis of existing multiple sclerosis (MS) data sets, a new measurement approach is proposed. The approach is based on quantitative functional composites that consist of simple quantitative measures from the major clinical dimensions of MS combined into a single score. Quantitative functional composites are likely to provide improved precision and sensitivity in future MS clinical trials. Studies necessary to further refine quantitative functional composites as useful MS clinical trial outcomes are delineated.

Clinical Trials as Topic↗
PubMed1997

Expression and characterization of human beta-secretase candidates metalloendopeptidase MP78 and cathepsin D in beta APP-overexpressing cells.

Human beta-secretase candidates, MP78 (h-MP78, EC 3.4.24.15) and cathepsin D (Cat D, EC 3.4.23.5), were evaluated for their ability to enhance amyloid-beta-protein (A beta) secretion when overexpressed in beta APP-containing cells. HEK-293 cells stably co-expressing h-MP78 or Cat D and h-beta APP695 were metabolically labeled with [35S]methionine and A beta secretion was quantified in the conditioned media by immunoprecipitation and ELISA without showing any significant increase in A beta production. Because Cat D is known to have a higher affinity for APP-substrate containing the Swedish familial Alzheimer's disease double mutation (SFAD, K595N and M596L substitutions in beta APP695) than for the wild type substrate [Dreyer et al., Eur. J. Biochem., 224 (1994) 265-271], the effect of Cat D overexpression was tested in a HEK293/beta APPSFAD stable cell line. ELISA analysis of the conditioned media from these cells did also not reveal any increase in A beta generation. In addition, recombinant h-MP78 purified from E. coli cleaved an APP-derived substrate spanning the beta-secretase site (ISEVKMD1AEFRHDS) at multiple sites, but the beta-site cleavage was only a minor one; cleavage occurred predominantly at K-M and E-F bonds. Human liver Cat D also cleaved the same substrate at multiple sites, yet the major cleavage at pH 4.0 occurred at the amyloidogenic D1 site. These findings indicate that h-MP78 does not have the cleavage specificity required for a beta-secretase protease and although Cat D fulfilled the amyloidogenic cleavage specificity, the results of the co-expression experiments make both enzymes less likely candidates as relevant beta-secretases.

Amino Acid Sequence↗
PubMed1997

Contrasting actions of celiprolol and metoprolol on cardiac performance in normal volunteers.

A double-blind, randomized, placebo-controlled comparison of metoprolol (50 mg) and celiprolol (200 mg) was undertaken in nine normal volunteers. Rest and exercise (supine bicycle) hemodynamics were assessed at 0, 2, 4, 6, and 8 hours following single oral doses of medication administered at weekly intervals. The influence of the ancillary pharmacological properties of metoprolol and celiprolol on cardiac pumping indices was assessed from heart rate and peak aortic acceleration (pkA-Exerdop). Following placebo, the heart rate and pkA increased progressively with exercise duration and workload. Following metoprolol 50 mg, the heart rate (-9.7 beat/min at 75 watts exercise) and pkA decreased. The blunting of acceleration was greater at higher exercise workloads (-6.7 m/sec2 at 75 watts exercise). Celiprolol reduced heart rate (-6.9 beat/min at 75 watts exercise) without a change in pkA. The heart rate/pkA relationship showed significant parallel displacement, downwards after metoprolol but upwards after celiprolol. Thus, for a given heart rate increment there was a greater decrease in pkA after metoprolol compared with celiprolol. The different ancillary pharmacological profiles of metoprolol and celiprolol resulted in contrasting hemodynamic profiles. The observed differences in the heart rate/pkA relationships may be attributable to the peripheral actions of these agents. The therapeutic relevance of the better maintained cardiac pumping indices on celiprolol for ischemic patients with impaired cardiac function warrants further investigation.

Adrenergic beta-Antagonists↗
PubMed1997

Traumatic brain injury/chronic pain syndrome: a case comparison study.

OBJECTIVE: To identify the pretreatment characteristics and progress in treatment and outcomes of chronic pain patients, with and without concomitant traumatic brain injury (TBI). DESIGN AND PATIENTS: Retrospective cohort study of 12 consecutive patients in a chronic pain treatment program who were discovered to have previously untreated brain injury and a cohort of 12 chronic pain patients from the same program matched for age and sex who did not have brain injury. SETTING: Interdisciplinary university-based outpatient rehabilitation medicine clinic. MAIN OUTCOME MEASURES: Length of time in treatment and vocational outcomes. RESULTS: A surprising number of patients referred for treatment of chronic pain were found to have history and symptoms indicative of previously untreated or undiagnosed mild traumatic brain injury (n = 21 of 65). Of these, 12 received therapy for both their brain injury and chronic pain. The 12 treated, dual diagnosed patients did not differ in terms of education, employment status, or marital status from the chronic pain patients. Those with TBI were more likely to have sustained an automobile injury and less likely to have a work-related injury. On admission, 25% of each group were working, and at discharge, that proportion reached 75% for each group. Those with TBI required significantly longer treatment (459 consecutive days) from intake to discharge compared with the control group (295 days). CONCLUSION: Patients who exhibit memory or concentration problems, who express confusion about their diagnosis, who were injured in an automobile accident, or who complain of pain in the head, neck, or arms should be questioned about the possibility of concurrent TBI. Most of these patients can achieve successful employment outcomes, however, the TBI group may require a longer treatment time.

Adult↗
PubMed1997

Reviewing the value of clinical audit: is now the time for a change?

Many different activities have been defined for the effective use of clinical audit. Proposes a method of linking the practice and outcome of audit with the Trust business people, setting out criteria methodology and background following a two-year research study.

Confidentiality↗
PubMed1996

Deregulated expression of c-myc in megakaryocytes of transgenic mice increases megakaryopoiesis and decreases polyploidization.

Platelets, essential for vascular integrity and hemostasis, fragment from polyploid megakaryocytes, characterized by their endomitotic cell cycle. We studied the influence of overexpression of c-myc oncogene on megakaryopoiesis and endomitosis in vivo, using transgenic mice carrying c-myc fused to the estrogen receptor under the control of the platelet factor 4 (PF4) megakaryocyte-specific promoter. The rationale behind this strategy was to obtain controlled overexpression of an active c-Myc, depending on the estrogen level in the mouse circulation. Analysis of these transgenic mice revealed that the bone marrow of female transgenic mice or of estrogen-injected male transgenic mice, but not of age-matched transgenic males nor nontransgenic females, contained frequent immature myeloid cells and an increased number of megakaryocytes. Deregulated expression of c-Myc shifted the normal ploidy profile of megakaryocytes due to a significant increase in proliferating megakaryocytes and a decrease in the fraction of ploidizing cells. These transgenic mice represent a novel in vivo model for a Myc-induced myeloproliferative disorder which can be controlled.

Animals↗