PubMed Health⌕ Search

Biomedical subjects

C Bell

Publications and source records attributed to C Bell.

At least 55 records · Page 3Linked to original sources
PubMed2000

Use of ambulatory electrocardiography for the detection of paroxysmal atrial fibrillation in patients with stroke. Canadian Task Force on Preventive Health Care.

BACKGROUND: Patients with stroke commonly undergo investigations to determine the underlying cause of stroke. These investigations often include ambulatory electrocardiography to detect paroxysmal atrial fibrillation. There is conflicting evidence in the literature regarding whether routine ambulatory electrocardiography should be performed in all or selected stroke patients. This paper reviews the available evidence on (1) the yield of ambulatory electrocardiography in detecting paroxysmal atrial fibrillation in patients with stroke or transient ischemic attack and (2) the effectiveness of anticoagulation in preventing recurrent stroke in patients with paroxysmal atrial fibrillation. METHODS: A MEDLINE search for primary articles was performed, and the references were reviewed manually. In addition, citations were obtained from experts. The evidence was systematically reviewed using the evidence-based methodology of the Canadian Task Force on Preventive Health Care. RESULTS: Ambulatory electrocardiography can detect atrial fibrillation not found on initial electrocardiogram in between 1% and 5% of people with stroke. Ambulatory electrocardiography is generally safe. The risk of recurrent stroke in the setting of paroxysmal atrial fibrillation is uncertain, but appears to be similar to that seen with chronic atrial fibrillation (about 12% per year). Therapy with warfarin may reduce this risk by about two-thirds as compared to placebo. The annual risk of major bleeding with warfarin therapy is between 1% and 3% but rates for individual patients depend on various specific risk factors. INTERPRETATION: There is insufficient evidence to recommend for or against the use of ambulatory electrocardiography for the detection of paroxysmal atrial fibrillation in either selected or unselected patients with stroke (C Recommendation). There is fair evidence to recommend therapy with warfarin for patients with stroke and paroxysmal atrial fibrillation (B Recommendation).

Anticoagulants↗
PubMed2000

Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis.

Familial expansile osteolysis (FEO, MIM 174810) is a rare, autosomal dominant bone disorder characterized by focal areas of increased bone remodelling. The osteolytic lesions, which develop usually in the long bones during early adulthood, show increased osteoblast and osteoclast activity. Our previous linkage studies mapped the gene responsible for FEO to an interval of less than 5 cM between D18S64 and D18S51 on chromosome 18q21.2-21.3 in a large Northern Irish family. The gene encoding receptor activator of nuclear factor-kappa B (RANK; ref. 5), TNFRSF11A, maps to this region. RANK is essential in osteoclast formation. We identified two heterozygous insertion mutations in exon 1 of TNFRSF11A in affected members of four families with FEO or familial Paget disease of bone (PDB). One was a duplication of 18 bases and the other a duplication of 27 bases, both of which affected the signal peptide region of the RANK molecule. Expression of recombinant forms of the mutant RANK proteins revealed perturbations in expression levels and lack of normal cleavage of the signal peptide. Both mutations caused an increase in RANK-mediated nuclear factor-kappaB (NF-kappaB) signalling in vitro, consistent with the presence of an activating mutation.

Base Sequence↗
PubMed2000

Steroid responsive polyneuropathy in a family with a novel myelin protein zero mutation.

OBJECTIVE: To report a novel hereditary motor and sensory neuropathy (HMSN) phenotype, with partial steroid responsiveness, caused by a novel dominant mutation in the myelin protein zero (MPZ) gene. Most MPZ mutations lead to the HMSN type I phenotype, with recent reports of Déjérine-Sottas, congenital hypomyelination, and HMSN II also ascribed to MPZ mutations. Differing phenotypes may reflect the effect of particular mutations on MPZ structure and adhesivity. METHODS: Clinical, neurophysiological, neuropathological, and molecular genetic analysis of a family presenting with an unusual hereditary neuropathy. RESULTS: Progressive disabling weakness, with positive sensory phenomena and areflexia, occurred in the proband with raised CSF protein and initial steroid responsiveness. Nerve biopsy in a less severely affected sibling disclosed a demyelinating process with disruption of compacted myelin. The younger generation were so far less severely affected, becoming symptomatic only after 30 years. All affected family members were heterozygous for a novel MPZ mutation (Ile99Thr), in a conserved residue. CONCLUSIONS: This broadens the range of familial neuropathy associated with MPZ mutations to include steroid responsive neuropathy, initially diagnosed as chronic inflammatory demyelinating polyneuropathy.

Adult↗
PubMed2000

Involving families in an urban HIV preventive intervention: how community collaboration addresses barriers to participation.

This article addresses the increasing need within urban communities for effective, culturally relevant HIV prevention programs. The recruitment efforts of a family-based prevention program aimed at promoting health and preventing HIV risk exposure in urban, African American fourth and fifth grade children living in a community with high rates of HIV infection is detailed. The program, referred to as the CHAMP (Chicago HIV Prevention and Adolescent Mental Health Project) Family Program, is overseen by a collaborative partnership of community parents, school staff, and university-based researchers (Paikoff & McKay, 1995). The recruitment strategies developed as a result of this community-research collaboration are described. Preliminary results of the project's efforts to reach out to families within the targeted, inner-city community are presented.

Black or African American↗
PubMed1999

Monoclonal antibodies that distinguish between two related digitalis glycosides, ouabain and digoxin.

The exogenous digitalis glycosides, ouabain and digoxin, have been widely used in humans to treat congestive heart failure and cardiac arrhythmias. Several reports have also pointed to the existence of endogenous ouabain- and digoxin-like compounds, but their precise roles in mammalian physiology and various disorders of the circulation are not clear. In an attempt to produce specific Abs for the purification and identification of endogenous ouabain-like compounds, somatic cell fusion was used to produce mAbs specific for ouabain. Our attempts to produce ouabain-specific mAbs were unsuccessful when ouabain was coupled to exogenous proteins such as bovine gamma-globulins, BSA, and human serum albumin. However, when ouabain was coupled to an Ab of A/J mice origin and the same strain of mouse was used for immunization with ouabain-Ab conjugate, three Abs (1-10, 5A12, and 7-1) specific for ouabain were obtained. In assays of fluorescence quenching and saturation equilibrium with tritiated ouabain, Ab 1-10 exhibited 200 nM affinity for ouabain. These three mAbs are distinguished from existing Abs to ouabain and digoxin by their specificity for ouabain and lack of cross-reactivity with digoxin. Specificity studies showed that the loss of cross-reactivity was correlated with the presence of a hydroxyl group at either position 12beta (digoxin) or 16beta (gitoxin) of the steroid ring. These Abs can be used to develop assays for detection and characterization of ouabain-like molecules in vivo.

Animals↗
PubMed1999

Aptamer affinity chromatography: combinatorial chemistry applied to protein purification.

The systematic evolution of ligands by exponential enrichment process is a combinatorial chemistry method that allows the identification of specific oligonucleotide sequences, known as aptamers, that bind to a desired target molecule with high affinity and specificity. Here, a DNA-aptamer specific for human L-selectin was immobilized to a chromatography support to create an affinity column. This column was effectively applied as either the first or second step in the purification of a recombinant human L-selectin-Ig fusion protein from Chinese hamster ovary cell-conditioned medium. The fusion protein was efficiently bound to the column and efficiently eluted by gentle elution schemes. Application of the aptamer column as the initial purification step resulted in a 1500-fold purification with an 83% single step recovery. These results demonstrate that oligonucleotide aptamers can be effective affinity purification reagents.

Animals↗
PubMed1999

Heterochromatic silencing of Drosophila heat shock genes acts at the level of promoter potentiation.

In a variety of organisms, genes placed near heterochromatin are transcriptionally silenced. In order to understand the molecular mechanisms responsible for this block in transcription, high resolution in vivo chromatin structure analysis was performed on two heat shock genes, hsp26 and hsp70. These genes normally reside in euchromatin where GAGA factor and RNA Pol II are present on the promoter prior to heat shock induction. P-element transformation experiments led to the identification of stocks in which these two genes were inserted within heterochromatin of the chromosome 4 telomeric region. These transgenes exhibit silencing that is partially suppressed by mutations in the gene encoding HP1. Micrococcal nuclease analysis revealed that the heterochromatic transgenes were packaged in a more regular nucleosome array than when located in euchromatin. High resolution DNase I analysis demonstrated that GAGA factor and TFIID were not associated with these promoters in heterochromatin; potassium permanganate experiments showed a loss of Pol II association. Taken together, these data suggest that occlusion of trans-acting factors from their cis- acting regulatory elements leading to a block in promoter potentiation is a mechanism for heterochromatin gene silencing.

Animals↗
PubMed1999

On the structure of endogenous ouabain.

The ouabain-like sodium pump inhibitor in mammals (so-called "endogenous ouabain") has been considered a subtle structural isomer of ouabain. Its structural investigation, however, has long been hindered by the paucity of sample material. Our recent purification of endogenous ouabain (3 micrograms) from bovine hypothalamus allowed the measurement of its 1H-NMR. The obtained spectrum as well as reexamination of past microscale structural studies on endogenous ouabain led us to identify the purified material as ouabain in an unusual manner. It turned out that the structural analysis had been complicated by a facile ouabain-borate complexation in borosilicate glassware. In retrospect, it is not surprising that the polyhydroxylated ouabain molecule serves as a polydentate ligand to inorganic species. In its physiological environment, ouabain may exist as some unknown complex. The chemical species giving rise to the reported biological activities of hypothalamic inhibitory factor preparations remain to be clarified.

Animals↗
PubMed1999

Oligonucleotide NX1838 inhibits VEGF165-mediated cellular responses in vitro.

VEGF (vascular endothelial growth factor) overproduction has been identified as a major factor underlying pathological angiogenesis in vivo, including such conditions as psoriasis, macular degeneration, and tumor proliferation. Endothelial cell tyrosine kinase receptors, KDR and Flt-1, have been implicated in VEGF responses including cellular migration, proliferation, and modulation of vascular permeability. Therefore, agents that limit VEGF-cellular interaction are likely therapeutic candidates for VEGF-mediated disease states (particularly agents blocking activity of VEGF165, the most frequently occurring VEGF isoform). To that end, a nuclease-resistant, VEGF165-specific aptamer NX1838 (2'-fluoropyrimidine, RNA-based oligonucleotide/40-kDa-PEG) was developed. We have assessed NX1838 inhibition of a variety of cellular events associated with VEGF, including cellular binding, signal transduction, calcium mobilization, and induction of cellular proliferation. Our data indicate that NX1838 inhibits binding of VEGF to HUVECs (human umbilical vein endothelial cells) and dose-dependently prevents VEGF-mediated phosphorylation of KDR and PLCgamma, calcium flux, and ultimately VEGF-induced cell proliferation. NX1838-inhibition of VEGF-mediated cellular events was comparable to that observed with anti-VEGF monoclonal antibody, but was ineffective as an inhibitor of VEGF121-induced HUVEC proliferation. These findings, coupled with nuclease stability of the molecule, suggest that NX1838 may provide therapeutic utility in vivo.

Calcium Signaling↗
PubMed1999

Mechanisms of action of selective serotonin reuptake inhibitors in the treatment of psychiatric disorders.

Selective serotonin reuptake inhibitors (SSRIs) have demonstrated efficacy in depression and anxiety disorders. This raises the question of how the single action of serotonin reuptake inhibition can improve several psychiatric conditions. In order to understand this apparent paradox it is necessary to consider where SSRIs act in the pathogenic process underlying depression or anxiety disorders. Tryptophan depletion has been used extensively in research into depression and has shown that, in patients receiving an SSRI whose depression is in remission, depleting serotonin leads to recurrence of the disorder. Similar results have been found for panic disorder. This suggests that increased levels of serotonin are necessary in the synapse for the SSRI to be effective in the treatment of depression and panic disorder. In obsessive compulsive disorder, depletion of serotonin in patients recovered on an SSRI does not cause relapse; receptor adaptation may be more important. Variations within the SSRI drug class, such as the selectivity ratios for serotonin versus noradrenaline uptake, elimination half-life, and affinity for the 5-HT2 receptor have been identified and may be important determinants of efficacy, side effects and clinical use.

Anxiety Disorders↗
PubMed1999

Effect of probe design on accuracy and reliability of pulse oximetry in pediatric patients.

STUDY OBJECTIVE: To determine if the traditional band-wrap disposable pulse oximeter probe is more accurate or reliable for oxygen monitoring in children than the reusable clip-type probe. DESIGN: Prospective, observational clinical study. SETTING: Operating room of a large university hospital. PATIENTS: 18 children 11 years of age or younger, who were scheduled for general anesthesia with placement of an intraarterial catheter. INTERVENTIONS: Pulse oximetry values were obtained using both band and clip probes of three pulse oximeters (Nellcor, Hayward CA; Novametrix, Wallingford, CT; Ohmeda, Boulder, CO) and compared with simultaneous hemoximetry values. Dropout rate (percent of down time) also was recorded for each probe-machine combination. MEASUREMENTS AND MAIN RESULTS: Data were analyzed using bias and precision and t-test. p < 0.05 is considered significant. Bias (mean SpO2-SaO2) is less than 2% for all probe-machine combinations. The range of error observed between SpO2 and SaO2 for all data points was greatest using the Nellcor band (27.8%) and least using the Ohmeda band (11.4%). In cyanotic children, the greatest bias and precision were observed with Nellcor band (N = 11, -5.12 +/- 9.74) and the best agreement with Novametrix band (N = 17, 0.08 +/- 4.21). The difference in bias for any test units above or below the median weight of 13.75 kg did not vary by more than 1%. Dropout rate was minimal for all units in nonbypass situations. After cardiopulmonary bypass, no data dropout was observed with Ohmeda band; observed down time with the other units varied between 34% and 55%. CONCLUSIONS: The type of probe selected has little effect on accuracy of pulse oximetry in children. After cardiopulmonary bypass, using the Ohmeda band combination may improve the likelihood of obtaining consistent readings and decreasing down time.

Anesthesia, General↗
PubMed1999

Effect of peripheral perfusion on accuracy of pulse oximetry in children.

STUDY OBJECTIVE: To examine the effect of perfusion on accuracy of two pulse oximeters in children and to determine thresholds of perfusion below which these pulse oximeters become inaccurate or cease to function. DESIGN: Prospective, observational clinical study. SETTING: Operating room of a large university hospital. PATIENTS: 19 children 10 years of age or less, who were scheduled for general anesthesia with placement of an intraarterial catheter. INTERVENTIONS: A radial artery catheter, laser Doppler probe, skin temperature sensor, and band probes of two oximeters, Ohmeda 3700 (Boulder, CO) and Nellcor N200 (Hayward, CA), were attached to the same hand. Baseline pulse oximeter and Doppler readings were obtained with simultaneous hemoximetry (AVL Model 912 CO-Oxylite, Roswell, GA), skin and esophageal temperatures, total hemoglobin, and transduced arterial pressure. Readings of all parameters (n = 94) were obtained during periods of low perfusion or by occluding the upper arm to 70% to 100% of systolic pressure. MEASUREMENTS AND MAIN RESULTS: Bias (SpO2-SaO2) of each oximeter is compared to each perfusion variable (age, weight, core and skin temperature, hemoglobin concentration, pulse pressure, and percent flow by laser Doppler) to determine effect on accuracy. Data were analyzed using backward multivariate linear regression, Pearson correlation coefficients, and independent paired t-test. p < 0.05 was considered significant. Less than 2% bias is seen with either oximeter (Nellcor 1.55 +/- 2.33, Ohmeda 0.78 +/- 2.25). Independent predictors of bias for each machine include weight (r = -0.376; p < 0.001) and pulse pressure (r = 0.250; p = 0.021) for the Nellcor, and weight (r = -0.390; p < 0.001), percent flow by Doppler (r = 0.220; p = 0.035), and core temperature (r = 0.307; p = 0.003) for the Ohmeda. However, using predetermined thresholds for each variable, only skin temperature below 30 degrees C is identified as a significant predictor of oximeter inaccuracy. CONCLUSIONS: At the parameters explored in this study, the selected seven perfusion variables (age, weight, core and skin temperature, hemoglobin concentration, pulse pressure, and percent flow by laser Doppler) have little effect on accuracy of pulse oximetry in children.

Age Factors↗
PubMed1999

Decreased vascular permeability response to substance P in airways of genetically hypertensive rats.

1. The inbred genetically hypertensive strain (GH) of the Otago Wistar rat possesses more sensory neurons containing the neuropeptide substance P (SP) than does its genetically related control normotensive strain. 2. As SP contributes to airway inflammation by increasing microvascular permeability, we assessed the extravasation of Evans Blue dye in trachea and main bronchus of anaesthetized GH and control rats, in the presence of endogenous (capsaicin-liberated) or exogenous SP. 3. Following intravenous administration of either capsaicin (75 microg kg(-1)) or SP (3.3 nmol kg(-1)), extravasation of Evans Blue in airways from GH rats was only about 60% of that in airways of control rats. This difference was not gender-specific and responses to capsaicin were abolished by pretreatment with a selective NK1 receptor antagonist SR 140333 (360 nmol kg(-1)). 4. By contrast, the extravasation of dye caused by intravenous 5-hydroxytryptamine (0.5 micromol kg(-1)) was similar in magnitude in both GH and control strains. 5. Falls in systemic arterial blood pressure in response to exogenous SP (0.1-3 nmol kg(-1)) or acetylcholine (0.2-2 nmol kg(-1)) were also very similar between strains, but those in response to capsaicin (75 microg kg(-1)) in the GH rats were about double those in control rats. The hypotensive response to SP was abolished by SR 140333, but that to capsaicin was unaffected. 6. Our results indicate that the increased peripheral innervation density by SP-nerves in GH rats is accompanied by reduced inflammatory responses to SP. This does not involve decreased vasodilator potency of SP and is therefore probably related to altered endothelial responsiveness.

Animals↗
PubMed1999

Genome scan for human obesity and linkage to markers in 20q13.

Obesity is a highly prevalent, multigenic trait that predicts increased morbidity and mortality. Here we report results from a genome scan based on 354 markers in 513 members of 92 nuclear families ascertained through extreme obesity and normal body weight. The average marker interval was approximately 10 cM. We examined four correlated obesity phenotypes, including the body-mass index (BMI) (both as a quantitative trait and as a discrete trait with a threshold of BMI > or /=30 kg/m2) and percentage of fat (both as a quantitative trait and as a discrete trait with a threshold of 40%) as assessed by bioelectrical impedance. In the initial stage of the genome scan, four markers in 20q gave positive evidence for linkage, which was consistent across most obesity phenotypes and analytic methods. After saturating 20q with additional markers (25 markers total) in an augmented sample of 713 members from 124 families, we found linkage to several markers in a region, 20q13, previously implicated in both human and animal studies. Three markers (D20S107, D20S211, and D20S149) in 20q13 had empirical P values (based on Monte Carlo simulations, which controlled for multiple testing) < or /=. 01 for single-point analysis. In addition, the parametric, affecteds-only analysis for D20S476 yielded a LOD score of 3.06 (P=. 00009), and the affected-sib-pair test yielded a LOD score of 3.17 (P=.000067). Multipoint analyses further strengthened and localized these findings. This region includes several plausible candidate genes for obesity. Our results suggest that one or more genes affecting obesity are located in 20q13.

Black People↗