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J Armstrong

Publications and source records attributed to J Armstrong.

At least 19 recordsLinked to original sources

Vascular delivery of c-myc antisense from cationically modified phosphorylcholine coated stents.

c-Myc is involved in the formation of neointimal hyperplasia. We investigated in vitro, ex vivo and in vivo release of antisense c-myc from cationically modified phosphorylcholine-coated stents, as well as the effects on c-Myc expression and neointima formation in a porcine coronary stent model. In vitro experiments were performed to determine optimal loading of stents with antisense. Stents loaded with labelled antisense were deployed in porcine arteries ex vivo and in vivo. Antisense was detected in the vessel wall directly surrounding the stent of pig carotid and coronary artery up to 48 h after stent deployment. Nuclear uptake was observed in endothelial and vascular smooth muscle cells. Labelled antisense within peripheral tissues in vivo was <1.0% of that within stented arterial segments. Control and antisense loaded stents implanted into 10 pig coronary arteries and analysed at 28 days post-stenting showed that lumen area within the antisense stents was significantly increased (i.e. 30.5% greater, P<0.01), whilst both neointimal area and neointimal thickness were significantly reduced (17.5% and 19.5%, respectively, P<0.01) compared to control stents. Cationically modified phosphorylcholine coated stent-based delivery of c-myc antisense is feasible with minimal systemic delivery and is associated with a reduction of in-stent neointimal hyperplasia in pig coronary arteries.

Animals↗

Bicalutamide (Casodex) 150 mg plus standard care in early non-metastatic prostate cancer: results from Early Prostate Cancer Trial 24 at a median 7 years' follow-up.

Trial 24, one of three ongoing trials in the Early Prostate Cancer programme, is evaluating the efficacy and tolerability of bicalutamide (Casodex) 150 mg following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with early, non-metastatic prostate cancer. At 7 years' median follow-up, addition of bicalutamide significantly improved objective progression-free survival (PFS) for patients with locally advanced disease, reducing the risk of progression by 34% versus standard care alone (hazard ratio 0.66; 95% confidence interval 0.55, 0.79; P<0.001). In localized disease, a significant difference in objective PFS was not found. There was no significant difference in overall survival.

Anilides↗

Effects of fulvestrant 250mg in premenopausal women with oestrogen receptor-positive primary breast cancer.

Fulvestrant (Faslodex) reduces markers of hormone sensitivity and proliferation in postmenopausal women. This Phase II double-blind, randomised, multicentre study compared the effects of a single 250mg intramuscular dose of fulvestrant and placebo 14-21 days prior to surgery of curative intent on the oestrogen receptor (ER), progesterone receptor and Ki67 levels in 66 premenopausal women with ER-positive primary breast cancer. There were no statistically significant differences between fulvestrant and placebo with respect to any of the three markers analysed. The most common adverse events in both groups were nausea, headache and pyrexia. Fulvestrant 250mg had no effects on markers of hormone-sensitivity and proliferation in premenopausal women with primary breast cancer when measured at 14-21 days after injection. These findings suggest that a higher fulvestrant dose may be required in this patient population. Further clinical trials are necessary to evaluate the efficacy of fulvestrant in premenopausal women.

Adult↗

Are bone scans necessary in men with low prostate specific antigen levels following localized therapy?

PURPOSE: The prostate specific antigen level at which to recommend a bone scan after treatment of early prostate cancer is controversial. We identified the incidence of bone metastases at varying prostate specific antigen levels in asymptomatic men following radical prostatectomy, radiation therapy and watchful waiting. MATERIALS AND METHODS: Data were obtained from the Early Prostate Cancer trial comparing placebo with bicalutamide in addition to standard care for localized prostate cancer. As part of the trial patients were required to have routine bone scans regardless of prostate specific antigen levels. The prostate specific antigen levels were divided into subgroups and the incidence of positive bone scans was calculated for each group. RESULTS: The incidence of positive bone scans in patients treated with watchful waiting and given bicalutamide or placebo was low (0.7% to 3.2%) at prostate specific antigen levels less than 20 ng/ml. At greater than this level the sample sizes were smaller but there was a significant increase in the incidence of positive bone scans. In the groups treated with radiation therapy or radical prostatectomy, regardless of the addition of bicalutamide, the incidence of positive bone scans was low (0.2% to 1.4%) at prostate specific antigen levels less than 5 ng/ml. The sample sizes were smaller at prostate specific antigen levels greater than 5 ng/ml so the results are harder to interpret. CONCLUSIONS: Bone scans can be confidently eliminated in the followup of patients with early prostate cancer after standard care of those with prostate specific antigen levels less than 5 ng/ml. This level can be increased to 20 ng/ml with caution in those patients treated with watchful waiting.

Androgen Antagonists↗

Hospital transmission of hepatitis B virus in the absence of exposure prone procedures.

In February and in June 1998, two people developed acute hepatitis B following in-patient care in a district general hospital. Initial enquiries indicated their infections were not attributable to staff undertaking exposure-prone procedures (EPPs). We report the findings and implications of the subsequent investigation: a multi-disciplinary, multi-agency investigation, including molecular epidemiological analysis. Occupational Health records showed that staff involved in EPPs with the patients were HBsAg negative. No contact between the patients was identified nor were there failures in sterilization. The patients' HBV strains were identical, indicating a common source. A total of 231 out of 232 staff who might have treated either patient were tested for HBsAg; the remaining doctor, working abroad, was HBsAg- and HBeAg-positive and had the same HBV strain as the patients. On two occasions the doctor's hand had been cut while breaking glass vials, but there was no documentation linking these events to the two patients. The doctor had been vaccinated in 1993 and tested for anti-HBs prior to commencing work in 1997. The doctor was recalled to Occupational Health but did not attend and was not followed up. In total, 4948 patients potentially treated by the doctor received an explanatory letter and 3150 were tested for HBsAg. Only one was positive, and HBV sequencing showed no link to the doctor. Occasionally transmission of HBV from heath-care workers can occur in a non-EPP setting and the implications of this require examination by those setting national policy. Occupational Health Services should investigate clinical heath-care workers who do not respond to vaccination. They should ensure HBV carriers are identified and offer them appropriate advice to prevent transmission to patients.

Adult↗

Rhizome phyllosphere oxygenation in Phragmites and other species in relation to redox potential, convective gas flow, submergence and aeration pathways.

Underground rhizomes of emergent aquatic macrophytes are important for perennation, vegetative spread, competition and anchorage. In four species we examined the potential for the development of oxidized phyllospheres around rhizome apical buds, similar to the protective oxygenated rhizospheres around roots. Redox potentials and polarographic measurements of radial oxygen loss were recorded using platinum cathodes around the apical buds. The aeration pathway from atmosphere to phyllosphere was investigated anatomically and by applied pressurized gas flow. Redox potentials increased by +400, +45, +200 and +340 mV around rhizome apices of Phragmites australis, Oryza rhizomatis, Carex rostrata and Glyceria maxima, respectively. Radial oxygen loss from rhizome apices of Phragmites was increased by convective gas flow through the rhizome and by shoot de-submergence, and decreased by resistances applied within the aeration pathway and by shoot submergence. We conclude that oxygen passes via internal gas-space connections between aerial shoot, rhizome and underground buds and into the phyllosphere regions via scale-leaf stomata and surfaces on the buds. We suggest that oxidized phyllospheres may protect rhizome apices against phytotoxins in waterlogged soils, just as oxidized rhizospheres protect roots.

Cyperaceae↗

Letting the family know: balancing ethics and effectiveness when notifying relatives about genetic testing for a familial disorder.

OBJECTIVE: To increase the awareness among at risk relatives of the availability of genetic testing for a familial disorder while respecting their autonomy and privacy. METHODS: This was a comparison of preintervention and postintervention cohorts of families carried out in a state wide clinical service providing genetic counselling and testing for people at risk of familial adult onset cancer. Unaffected relatives who were not clients of the service in 74 kindreds with familial mutations causing familial breast and ovarian cancer, hereditary non-polyposis colorectal cancer, or Cowden syndrome were included in the study. In the baseline cohort (41 kindreds), family members who were clients of the clinical service and had been shown to be carriers of mutations were asked to advise relatives that genetic testing was available. In the intervention cohort (33 kindreds), the clinical service obtained consent to advise at risk relatives by letter that genetic testing was available. The main outcome measures were: (a) proportion of unaffected first and second degree relatives of the proband in each family whose genetic status was clarified within 2 years of the mutation being identified in the family, and (b) concerns regarding privacy and autonomy voiced by relatives receiving these letters. RESULTS: In the baseline cohort, the average proportion of relatives in each family whose genetic status was clarified was 23%. In the intervention cohort, the average proportion of relatives in each family whose genetic status was clarified was 40% (p = 0.001). None of the relatives in the intervention cohort complained of a breach of privacy or autonomy. CONCLUSION: Clinical services can take an effective and proactive approach to notifying relatives who are not their clients of the availability of genetic testing without compromising principles of privacy and autonomy.

Adolescent↗

Spontaneous resolution of isolated Chiari I malformation.

INTRODUCTION: Spontaneous resolution of Chiari I abnormality is very rare. In most patients, the radiological abnormality either stays unchanged with time or deriorates. CASE REPORT: We present a male patient who was diagnosed at the age of 18 months as having radiological evidence of Chiari I malformation without syringomyelia, which had resolved 5 years later on a subsequent MR scan. At the time of initial diagnosis, he had been experiencing recurrent jerking movements of his body and was a sufferer of chronic renal failure. DISCUSSION: The symptoms were thought to be unrelated to the hindbrain hernia. Such spontaneous resolution of an isolated Chiari I malformation has only been described once more before, although resolution of hindbrain hernia associated with syringomyelia has been described before in several cases, albeit at single figures. The mechanism for such a natural evolution is not clear. CONCLUSION: This patient demonstrates that surgical treatment should not be considered hastily in patients with radiological evidence of Chiari I in the absence of convincing associated clinical symptoms.

Adolescent↗

Spinocerebellar ataxia type 2 (SCA2) with white matter involvement.

Two sisters presented with olivopontocerebellar atrophy, neuronal loss in the substantia nigra, intranuclear ubiquitin-, ataxin-2-positive inclusions in neurons, and severe demyelination and axon loss of the cerebral white matter with no accompanying inflammatory pathology. The genetic study demonstrated a 22/36 CAG triplet expansion in the SCA2 gene in one of the sisters; SCA1, SCA3, SCA6, SCA7, SCA8, SCA12, SCA17 and DRPL were ruled out in this patient. The present report shows that severe cerebral white matter pathology may occur in the context of SCA2.

Adult↗

A method for assessing accurate application of the Partin Tables in the pre-therapy evaluation of patients with prostate cancer.

AIMS: The treatment of prostate cancer is frequently influenced by the Partin Tables. This predictive model has been internally and externally validated since it was conceived, and has proved to be remarkably reliable and consistent. This paper proposes that, by using the statistical programme for the social sciences (SPSS) and receiver-operator characteristic curves, it is possible to detect institutions that apply this model sub-optimally. MATERIALS AND METHODS: This theory was supported by a PUBMED search using relevant search words. RESULTS: This is a novel technique with the potential to allow retrospective and prospective accrual of results. CONCLUSIONS: A systematic institutional review of how accurately a hospital assesses the clinical stage, Gleason score and PSA has the potential to increase an institution's predictive accuracy when it uses the Partin Tables. The proposed method allows for quantitation of the level of error and comparison of predictive accuracy between institutions. It also may be used as an internal outcome measure to assess improvement in a hospital's investigative procedures over time.

Humans↗

Bicalutamide ('Casodex') 150 mg in addition to standard care in patients with nonmetastatic prostate cancer: updated results from a randomised double-blind phase III study (median follow-up 5.1 y) in the early prostate cancer programme.

Trial 24 is one of three placebo-controlled trials within the ongoing bicalutamide ('Casodex') Early Prostate Cancer (EPC) programme evaluating bicalutamide 150 mg/day in addition to radical prostatectomy, radiotherapy or watchful waiting for T1b-4, any N, M0 prostate cancer. In Trial 24, at 5.1 y median follow-up, the addition of bicalutamide significantly (P < 0.0001) improved objective progression-free survival (PFS) and prostate-specific antigen PFS compared with standard care alone. There was no significant difference in overall survival (P = 0.746). In the context of the whole EPC programme, long-term bicalutamide is not appropriate for localised disease, yet provides advantages in delaying disease progression in patients with locally advanced prostate cancer.

Adult↗

Antigenic and genetic characterization of rabies viruses isolated from domestic and wild animals of Brazil identifies the hoary fox as a rabies reservoir.

Fifty Brazilian rabies viruses, collected from many different animal species and several regions of the country, were characterized by partial sequencing of the central, variable region of the P gene, a locus useful for sensitive molecular epidemiological studies. Phylogenetic analysis of the sequences, which included comparison with other rabies strains recovered from throughout the Americas, identified three main groups of Brazilian viruses, arbitrarily designated BRL-1 to BRL-3. BRL-1 was found in terrestrial carnivores and clusters with other American strains of the cosmopolitan lineage. BRL-2 comprised two distinct isolates, recovered from two species of non-haematophagous bats, that had evolutionary links to insectivorous-bat-derived strains of North America. BRL-3 consisted of isolates from vampire bats and from livestock species probably infected via contact with vampire bats. The terrestrial group was further subdivided into three subtypes: BRL-1a was associated exclusively with dogs and cats, while BRL-1b and BRL-1c were found exclusively in hoary foxes. These observations strongly support the role of the Brazilian hoary fox as a rabies reservoir. Screening of representative Brazilian rabies viruses against a collection of anti-rabies monoclonal antibodies (mAbs) identified a small panel of mAbs that could be used to discriminate between all Brazilian subgroups as defined by genetic classification in this study.

Animals↗

Familial Alzheimer disease associated with A713T mutation in APP.

Mutations in APP are associated with familial early-onset Alzheimer disease (FAD). Examination of the genomic sequence in one patient with FAD revealed a change located in the axon 17 of the APP gene at position 275329G>A (GenBank accession number: D87675; GI: 2429080); cDNA sequence 2137G>A (GenBank accession number: X06989; GI: 28720). This corresponds to the mutation A713T in APP. AD stage VI of neurofibrillary degeneration and stage C of Abeta-amyloid burden was found at the post-mortem neuropathological examination. Previous studies have suggested that the mutation A713T in APP is a silent mutation or polymorphism. However, we have not found this change in APP in a control population analyzed by the amplification-refractory mutation system (ARMS). It is concluded that A713T in APP is implicated in the pathogenesis of AD. Since the immunohistochemical study indicates that A713T mutation is not likely to relate with Abeta-amyloid processing, the causative role of this rare mutation remains to be warranted.

Alanine↗

Regulation of antigen-specific versus by-stander IgE production after antigen sensitization.

IgE is critical in the pathogenesis of allergic disorders. In this report, we investigated the differential regulation of antigen-specific and by-stander IgE. Ovalbumin (OVA) immunization did not increase IgE producing cells in the spleen, but significantly enhanced the intracellular IgE content of all IgE+ cells. In contrast, OVA induced a significant increase of IgE+ cells in the draining lymph nodes (LN). Furthermore, OVA-specific IgE was detected only in the ex vivo cultures of the draining LN but not the spleen cells, while total IgE was increased in both cultures. These results indicated that antigen-specific IgE was mainly produced in the draining LN, while the spleen was a major source for by-stander IgE. Anti-IL-4, but not anti-IL-13, antibody blocked the expansion of IgE producing cells in the draining LN as well as systemic OVA-specific and total IgE levels, indicating IL-4 was important in both antigen-specific IgE generation and total IgE upregulation.

Adjuvants, Immunologic↗

Molecular and antigenic characterization of rabies viruses from Iran identifies variants with distinct epidemiological origins.

A molecular epidemiological study of 48 recent rabies isolates recovered from cases reported throughout Iran identified three distinct viral variants, the evolutionary origins of which were identified by phylogenetic comparison with rabies viruses originating from Europe and Asia. Members of group 1 (15 isolates) were recovered from the northern half of the country only, while those of group 2 (31 isolates) were widely dispersed; both groups clustered within the widely disseminated cosmopolitan lineage. The two isolates of group 3 were detected in the northeastern tip of the country only and belonged to the Arctic strain. Rapid variant discrimination tools, employing restriction fragment length polymorphisms applied to amplified fragments of the viral genome, were devised whilst antigenic characterization of representative viruses identified a small panel of monoclonal antibodies that were also discriminatory. The future application of such methods should provide valuable epidemiological information on rabies incidence in Iran.

Amino Acid Sequence↗

Coexistence of social inequalities in undernutrition and obesity in preschool children: population based cross sectional study.

AIMS: To test for the coexistence of social inequalities in undernutrition and obesity in preschool children. METHODS: Retrospective, cross sectional, study of routinely collected data from 74 500 children aged 39-42 months in 1998/99. Main outcome measures were weight, height, sex, and age routinely recorded by health visitors. Body mass index (BMI) standardised for age and sex, relative to UK 1990 reference data, was used to define undernutrition (BMI <2nd centile) and obesity (BMI >95th centile; BMI >98th centile). Social deprivation was assessed as Carstairs deprivation category (1 = most affluent to 7 = most deprived). RESULTS: Both undernutrition (3.3%) and obesity (8.5% above 95th centile; 4.3% above 98th centile) significantly exceeded expected frequencies from UK 1990 reference data. Undernutrition and obesity were significantly more common in the more deprived families. Odds ratios in deprivation category 7 relative to category 1 were 1.51 (95% CI 1.22 to 1.87) for undernutrition (BMI <2nd centile) and 1.30 (95% CI 1.05 to 1.60) for obesity (BMI >98th centile). The cumulative prevalence of under and overnutrition (malnutrition) in the most deprived group was 9.5% compared to 6.9% in the least deprived group. CONCLUSIONS: Undernutrition and obesity are significantly more common than expected in young children and strongly associated with social deprivation. Both undernutrition and obesity have adverse short and long term health effects. Public health strategies need to tackle malnutrition (both undernutrition and obesity) in children and take into consideration the association with social deprivation.

Body Mass Index↗

The prevalence of obesity and undernutrition in Scottish children: growth monitoring within the Child Health Surveillance Programme.

OBJECTIVE: To assess whether anthropometric data, routinely collected as part of the Scottish Child Health Surveillance System (CHSP-PS, pre-school children; CHSP-S, school age children) could provide a means of monitoring/surveillance for obesity and undernutrition at national and health board level. DESIGN: A survey of 15 health boards and both surveillance systems to identify the nature of data collected, format of data, and extent to which data were accessible (e.g., via Information and Statistics Division of the Common Services Agency). Measurements of weight and height collected as part of the CHSP-PS and CHSP-S were extracted from ISD. They were then audited and missing values or implausible values quantified, and degree of dispersion of values used as an index of quality of measurements. SETTING: Health Board Child Health Surveillance Systems and Information and Statistics Division, Edinburgh. RESULTS: Data on height and weight are currently available for 9 health boards for pre-school children and 4 health boards for school age children. This represents coverage of around 80% of the pre-school child population. Analysis of a data extract from the 39-42 month check in 1998/99, used as an example, revealed that 8% of weight and height data were missing, and approximately 1% were implausible measures. Population and health board level estimates of prevalence of obesity and undernutrition were possible and are presented. Data on height and weight are routinely collected in school age children in all health boards, however only four health boards have growth data electronically available via the school CHSP. CONCLUSIONS: Growth data routinely collected as part of child health surveillance for Scotland can be used to estimate population prevalence of undernutrition and obesity. These can in turn be used to monitor trends at local and national level, to monitor achievement in relation to public health targets, identify risk factors and high risk groups, and to follow cohorts over time. We describe a system of surveillance for undernutrition and obesity and identify its strengths and weaknesses.

Adolescent↗