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Biomedical subjects

D Armstrong

Publications and source records attributed to D Armstrong.

At least 109 records · Page 6Linked to original sources
PubMed2000

HPLC analysis of lipid-derived polyunsaturated fatty acid peroxidation products in oxidatively modified human plasma.

BACKGROUND: Lipid peroxidation is a prominent manifestation of free radical activity and oxidative stress in biological systems. Diverse methodologies have been developed that measure a variety of lipid peroxidation products used as markers of lipid peroxidation processes. METHODS: Hydroxy and hydroperoxy polyunsaturated fatty acid (PUFA) peroxidation products were analyzed in human blood plasma by reversed-phase HPLC after liquid-liquid extraction of total lipids and alkaline hydrolysis of lipid esters to liberate free PUFAs. An isocratic mobile phase containing 1 g/L acetic acid-acetonitrile-tetrahydrofuran (52:30:18, by volume) over 60 min duration, with ultraviolet absorbance detection at 236 nm by photodiode array, enabled the resolution and quantification of 13 regioisomeric hydroxy and hydroperoxy PUFAs. RESULTS: As little as 250 microL of human plasma was utilized with an analytical range of 0.033-1.6 micromol/L for each compound. Intra- and interassay CVs for all compounds detected in normal or oxidatively modified human plasma were 3.2-11% and 4.7-12%, respectively. Analytical recoveries were 87-103%. Analysis of human plasma exposed to artificial oxidation with Cu(2+) ion and hydrogen peroxide, a free radical-generating reaction, showed marked increases in hydroxy and hydroperoxy PUFA concentrations. CONCLUSION: Lipid-derived hydroxy and hydroperoxy PUFAs may be useful as clinical markers of lipid peroxidation and oxidative stress in the peripheral circulation.

Chromatography, High Pressure Liquid↗
PubMed2000

[Effect of antioxidants on radical-initiated peroxidation of retinal homogenate].

PURPOSE: To compare the effect of antioxidants on radical-initiated peroxidation of retinal homogenate. METHODS: Lipid peroxides in bovine retinal homogenate were induced by 5 mM FeNO3 (Fe), 25 mM 2, 2'-azobis(2,4'-dimethylvaleronitrile) (lipid-soluble, AMVN) or 50 mM 2,2'-azobis (2-amidinoprpane) dihydrochloride (water-soluble, AAPH) and the preventive effects of antioxidants were measured. Phosphatidylcholine hydroperoxide (PC-OOH) was analyzed with high performance liquid chromatography (HPLC) as the endpoint biomarker. RESULTS AND CONCLUSION: Troglitazone, an oral hypoglycemic agent, inhibited PC-OOH production by Fe and AMVN. Therefore, it may be effective for protecting against oxidative stress on the inner surface plasma membranes and subcellular organelle. Quercetin has radical scavenging effects on both sides of the membrane, because it prevents PC-OOH production by AMVN or AAPH. These results demonstrate the usefulness of an in vitro screening test that can accurately and rapidly determine the capacity of an antioxidant against lipid peroxidation or oxidative stress.

Animals↗
PubMed2000

When questionnaire response rates do matter: a survey of general practitioners and their views of NHS changes.

This paper investigates whether general practitioners (GPs) who do not participate in questionnaire surveys (non-responders) hold different views on participation in primary care reorganisation than their more compliant colleagues. A survey of 72 GPs' involvement in a pilot primary care prescribing group elicited an initial response of 74%. Non-responders were then approached personally and persuaded to complete the questionnaire. Comparison of the responders and the non-responders showed that the latter did differ significantly from the responders in many of their views. This difference needs to be considered whenever the results of surveys are used to guide policy-making in the more corporate model of primary care that is now emerging.

Attitude of Health Personnel↗
PubMed1999

Multiorgan autonomic dysfunction in mice lacking the beta2 and the beta4 subunits of neuronal nicotinic acetylcholine receptors.

Transcripts for the beta2 and the beta4 nicotinic acetylcholine receptor (nAChR) subunits are found throughout the CNS and the peripheral nervous system. These two beta subunits can form heteromultimeric channels with any of the alpha2, alpha3, alpha4, or alpha5 subunits in heterologous expression systems. Nonetheless, the subunit composition of native nAChRs and the role of different nAChR subtypes in vivo remain unclear. We prepared null mutations for the beta2 and the beta4 genes and bred beta2-/-beta4-/- mice by mating mice of identical beta2-/-beta4+/- or beta2+/-beta4-/- genotype. The beta2-/- and the beta4-/- single-mutant mice grow to adulthood with no visible phenotypic abnormalities. The beta2-/-beta4-/- double mutants survive to birth but have impaired growth and increased perinatal mortality. They also present enlarged bladders with dribbling urination and develop urinary infection and bladder stones. The ocular pupils are widely dilated and do not constrict in response to light. Histological studies revealed no significant abnormalities of brain or peripheral tissues except for hyperplasia in the bladder mucosa of beta4-/- and beta2-/-beta4-/- mutants. Bladder strips from beta2-/-beta4-/- mice did not respond to nicotine but contracted when stimulated with a muscarinic agonist or electric field stimulation. Bladder strips from beta4 mutants did not respond to nicotine despite the absence of major bladder dysfunction in vivo. Acetylcholine-activated whole-cell currents were absent in superior cervical ganglion neurons from beta2-/-beta4-/- mice and reduced in neurons from beta4-/- mice. Although there is apparent redundancy and a superficially normal phenotype in beta2-/- and beta4-/- mice, physiological studies indicate major deficits in the beta4-/- mice. Our previous description of a similar phenotype in alpha3-/- mice and the current data suggest that the alpha3 and the beta4 subunits are major components in autonomic nAChRs. The phenotype of the beta2-/-beta4-/- and alpha3-/- mice resembles the autosomal recessive megacystis-microcolon-hypoperistalsis syndrome in humans.

Animals↗
PubMed1999

Implementing evidence based medicine in general practice: audit and qualitative study of antithrombotic treatment for atrial fibrillation.

OBJECTIVE: To determine the extent to which implementation of an evidence based treatment, antithrombotic treatment in atrial fibrillation, is possible in general practice. DESIGN: Audit and qualitative study of patients with atrial fibrillation and an educational intervention for patients judged eligible for antithrombotic treatment. SETTING: South east England. SUBJECTS: 56 patients with a history of atrial fibrillation. INTERVENTIONS: Assessment and interview to ascertain patients' views on antithrombotic treatment. MAIN OUTCOME MEASURES: Number of patients receiving antithrombotic treatment. RESULTS: Out of 13 239 patients, 132 had a history of atrial fibrillation of which 100 were at risk of thromboembolism. After the study, 52 patients were taking warfarin. Of the remaining 48 patients (of whom 41 were taking aspirin), eight were too ill to participate, 16 were unable to consent, four refused the interview, and 20 declined warfarin. Patients declining warfarin were inclined to seek a higher level of benefit than those taking it, as measured by the minimal clinically important difference. Qualitative data obtained during the interviews suggested that patients' health beliefs were important factors in determining their choice of treatment. CONCLUSION: Patients' unwillingness to take warfarin seemed to be a major factor in limiting the number who would eventually take it.

Atrial Fibrillation↗
PubMed1999

Megacystis, mydriasis, and ion channel defect in mice lacking the alpha3 neuronal nicotinic acetylcholine receptor.

The alpha3 subunit of the neuronal nicotinic acetylcholine receptor is widely expressed in autonomic ganglia and in some parts of the brain. The alpha3 subunit can form heteromultimeric ion channels with other alpha subunits and with beta2 and beta4 subunits, but its function in vivo is poorly understood. We prepared a null mutation for the alpha3 gene by deletion of exon 5 and found that homozygous (-/-) mice lacked detectable mRNA on Northern blotting. The -/- mice survive to birth but have impaired growth and increased mortality before and after weaning. The -/- mice have extreme bladder enlargement, dribbling urination, bladder infection, urinary stones, and widely dilated ocular pupils that do not contract in response to light. Detailed histological studies of -/- mice revealed no significant abnormalities in brain or peripheral tissues except urinary bladder, where inflammation was prominent. Ganglion cells and axons were present in bladder and bowel. Bladder strips from -/- mice failed to contract in response to 0.1 mM nicotine, but did contract in response to electrical field stimulation or carbamoylcholine. The number of acetylcholine-activated single-channel currents was severely reduced in the neurons of superior cervical ganglia in -/- mice with five physiologically distinguishable nicotinic acetylcholine receptor subtypes with different conductance and kinetic properties in wild-type mice, all of which were reduced in -/- mice. The findings in the alpha3-null mice suggest that this subunit is an essential component of the nicotinic receptors mediating normal function of the autonomic nervous system. The phenotype in -/- mice may be similar to the rare human genetic disorder of megacystis-microcolon-intestinal hypoperistalsis syndrome.

Animals↗
PubMed1999

Diagnostic accuracy of oropharyngeal cultures in infants and young children with cystic fibrosis.

The objective of this study was to assess the diagnostic accuracy of oropharyngeal (OP) cultures relative to simultaneous bronchoalveolar lavage (BAL) cultures in very young children with CF, and to examine the effects of bacterial density, age, and study cohort on diagnostic accuracy. Respiratory culture data were analyzed from three independent, prospective studies involving simultaneous collection of 286 OP and BAL cultures from 141 children with CF <5 years of age. For predicting any growth of Pseudomonas aeruginosa (Pa) from the lower airway in subjects </=18 months of age (mean age, 8 +/- 5 months), OP cultures had a sensitivity of 44% (95% CI 14%, 79%), specificity of 95% (90%, 99%), positive predictive value of 44% (14%, 79%), and negative predictive value of 95% (90%, 99%). Diagnostic accuracy was similar for Haemophilus influenzae (Hi). Specificity was significantly lower for Staphylococcus aureus (Sa). Sensitivity for all organisms improved if a positive lower airway culture was defined as >/=10(3) or >/=10(5) cfu/mL. Specificity for Pa declined significantly with increasing age. In children with CF <5 years of age, the specificity and negative predictive value of OP cultures for Pa are high, while the sensitivity and positive predictive value are poor. Thus, in this age range, a negative throat culture is helpful in "ruling out" lower airway infection with Pa. However, a positive culture does not reliably "rule in" the presence of Pa in the lower respiratory tract. These findings may have implications for study design and interpretation as well as clinical management of young children with CF.

Bacterial Infections↗
PubMed1999

Groalpha-mediated recruitment of neutrophils is required for elicitation of contact hypersensitivity.

The factors mediating recruitment of immune T cells to challenge sites during contact hypersensitivity (CHS) responses remain unclear. To investigate the role of chemokines during elicitation of CHS, the temporal expression of chemokine genes in hapten-challenged ears was tested. KC (the murine homologoue of Groalpha) was expressed 30 min following hapten challenge in naive and hapten-sensitized mice. A rabbit KC-specific antiserum inhibited elicitation of CHS when administered to sensitized mice prior to hapten challenge. Injecting either neutrophils or immune CD8(+) T cells into the ear tissue of immune animals before hapten challenge circumvented the KC antiserum-mediated inhibition of CHS. Neutrophil depletion also inhibited CHS and was circumvented by injecting either neutrophils or hapten-primed CD8(+) T cells into ears of sensitized mice followed by specific hapten challenge. These results indicate that KC-directed neutrophil infiltration of hapten challenge sites is required for elicitation of CHS and suggest that neutrophils mediate recruitment of the hapten-specific CD8(+) T cells that subsequently produce cytokines mediating the hypersensitivity response.

Animals↗
PubMed1999

Ex-vivo expansion of bone marrow progenitor cells for hematopoietic reconstitution following high-dose chemotherapy for breast cancer.

The use of hematopoietic growth factors, stromal monolayers, and frequent medium exchange allows the expansion of hematopoietic progenitors ex-vivo. We evaluated the use of ex-vivo expanded progenitor cells for hematopoietic reconstitution following high dose chemotherapy (HDC) in breast cancer patients. Patients with high-risk Stage II or metastatic breast carcinoma underwent bone marrow aspirations using general anesthesia. A total of 675-1125 x 10(6) mononuclear cells (MNC) were seeded for ex-vivo expansion for 12 days in controlled perfusion bioreactors (Aastrom Biosciences, Inc.). The bone marrow cultures, which included the stromal cells collected with the aspirate, were supplemented with erythropoietin, granulocyte-macrophage-colony stimulating factor (GM-CSF)/IL-3 fusion protein (PIXY 321), and flt3 ligand. Stem cell transplant was performed with expanded cells after HDC. A median bone marrow volume of 52.9 mL (range 42-187 mL) was needed to inoculate the bioreactors. Median fold expansion of nucleated cells (NC) and colony forming unit granulocyte-macrophage (CFU-GM) was 4.9 and 9.5, respectively. The median fold expansion of CD34+lin- and long-term culture-initiating culture (LTC-IC) was 0.42 and 0.32, respectively. Five patients were transplanted with ex-vivo expanded NC. Median days to an absolute neutrophil count > 500/microL was 18 (range 15-22). Median days to a platelet count > 20,000/microl was 23 (range 19-39). All patients had sustained engraftment of both neutrophils and platelets. Immune reconstitution was similar to that seen after HDC and conventional stem cell transplantation. We conclude that ex-vivo expansion of progenitor cells from perfusion cultures of small volume bone marrow aspirates, allows hematopoietic reconstitution after HDC.

Adult↗
PubMed1999

Immature astrocytes in Fukuyama congenital muscular dystrophy: an immunohistochemical study.

Recent studies of Fukuyama congenital muscular dystrophy have focused on abnormalities of the basement membrane in muscle and brain. The cerebral cortex has a unique basement membrane at the glia limitans, which is intimately related to astrocytes in the developing brain, and the basement membrane may be partially produced by the astrocyte. In this study the cerebral astrocytes in six patients with Fukuyama congenital muscular dystrophy, including two fetal patients, were characterized by immunohistochemical study. In fetal Fukuyama congenital muscular dystrophy, astrocytes reacted less to antibodies of glial fibrillary acidic protein, S-100 protein, and alphaB-crystallin than control astrocytes, but in postnatal Fukuyama congenital muscular dystrophy, astrocytes reacted more to these antibodies and displayed beading of processes. Moreover, vimentin was positive in the astrocytes of two postnatal Fukuyama congenital muscular dystrophy patients. This astrocytic appearance may suggest immaturity of astrocytes in Fukuyama congenital muscular dystrophy. Astrocytes exhibiting beaded cytoplasmic processes were prominent at the subpia of the cortex and around vessels. The authors hypothesize that these immature astrocytes are unable to participate in the function of the cortical basement membrane, which is defective in Fukuyama congenital muscular dystrophy. Studies of neurons and meninges were similar to those of control subjects.

Adolescent↗
PubMed1999

Amphotericin B with and without itraconazole for invasive aspergillosis: A three-year retrospective study.

BACKGROUND: Treatment of invasive aspergillosis is frequently unsuccessful, so innovations in therapy are needed. Clinical studies demonstrate that itraconazole may be an effective alternative to amphotericin B. Itraconazole also has been combined with amphotericin B in animal models of aspergillosis, but this regimen produced antagonistic effects. OBJECTIVES: To determine the role of itraconazole in the adjunctive treatment of invasive aspergillosis. METHODS: A review was conducted of all patients with definite or probable aspergillosis from January 1995 to December 1997 who were treated with conventional amphotericin B alone or in combination with itraconazole. RESULTS: Of 21 patients, 10 received amphotericin B and 11 received the combination. The two groups of patients were comparable clinically at baseline (including similar mean APACHE III scores). Both groups received similar doses and days of amphotericin B treatment. Of the patients who received combination therapy, nine (82%) were cured or improved, and of those who received only amphotericin B, five (50%) were cured or improved. CONCLUSIONS: This study demonstrates that itraconazole and amphotericin B given together are not clinically antagonistic and that the promise of combination therapy for aspergillosis should be evaluated further in a randomized clinical trial.

APACHE↗
PubMed1999

Monitoring the clearance of fetal RhD-positive red cells in FMH following RhD immunoglobulin administration.

Anti-RhD immunoglobulin was administered to RhD-negative women based on estimates of fetal bleed size obtained using a direct immunofluorescence flow cytometric technique employing a FITC-conjugated monoclonal human anti-D (BRAD 3). The effectiveness of the dose administered was assessed by (i) measuring the fraction of RhD-positive fetal cells in the maternal circulation at d0, and between d2 and d10 post RhD Ig administration, (ii) quantifying the amount of anti-D detectable in maternal plasma following RhD Ig injection in the perinatal period and (iii) assessing maternal serum for the presence of immune anti-D in follow-up samples taken 3 months to 3 years after delivery. Fifty-four women were assessed, 29 having fetal bleeds in excess of 4 mL. Follow-up samples were received from 20/29 mothers after RhD Ig administration; 43-99% and 69-99% of fetal cells had been cleared by d2/3 and d5/6, respectively, in 14/20 mothers, whereas less than 50% had been cleared in the remaining mothers. Long-term follow-up samples were obtained from eight of the 29 mothers (four with bleeds >/=20 mL, two with bleeds >95 mL): none had detectable anti-D in the serum 4 months to 3 years after delivery despite the persistence of up to 36% fetal RhD-positive cells in the maternal circulation six days after delivery.

Erythrocytes↗
PubMed1999

Bronchiectasis and bronchiolitis obliterans post respiratory syncytial virus infection: think again.

Respiratory syncytial virus (RSV) lower respiratory tract infections are common, yet long-term sequelae in previously healthy infants and children are rarely reported. We report a child who developed bronchiectasis and bronchiolitis obliterans following an RSV lower respiratory tract infection but in whom adenovirus was detected on stored serum. Co-infection with adenovirus is the likely cause for the bronchiectasis and bronchiolitis obliterans.

Bronchiectasis↗
PubMed1999

The outcome of pregnancy associated with amphetamine use.

Thirty cases of pregnancy associated with maternal amphetamine use were studied retrospectively fifteen out of the 30 women used amphetamines alone and the other 15 used other drugs in addition to amphetamines. Women who simultaneously used opiates were excluded from this analysis. Women were cared for in a multidisciplinary setting and all delivered in one hospital. With support all women were encouraged to discontinue drug use. There were 2 perinatal deaths, 1 from each group (amphetamines alone or amphetamines plus others). The mean birth weight were 2878 and 2959 grams respectively and gestational age 38.23 and 37.47 weeks respectively. If the whole group was divided into women who ceased amphetamine use and continued use in pregnancy, there was no marked difference between outcome in these 2 subgroups, however, the 2 perinatal deaths both occurred in women who continued amphetamine use. The risk of prematurity was 28.6% and low birth weight 25%, rates which were not reduced by an alteration in drug use.

Journal Article↗