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Biomedical subjects

S Dyer

Publications and source records attributed to S Dyer.

At least 19 recordsLinked to original sources

Molecular cytogenetic characterization of two non-MYCN amplified neuroblastoma cell lines with complex t(11;17).

The pediatric tumor neuroblastoma is characterized by a very variable, and at times unpredictable, pattern of clinical behavior, ranging from a benign localized tumor to an aggressive malignancy with poor prognosis. Standard clinical and pathological assessments do not always differentiate reliably between tumor subtypes and, therefore, genetic markers are now playing an increasingly important role in treatment decisions. MYCN oncogene amplification, for example, provides a useful marker of poor prognosis. However, less than one-half of all patients who present with, or who later develop, metastatic disease show MYCN amplification. Consequently, the identification of characteristic patterns of genetic alteration in the remaining tumors is of importance. In this report, we describe two new cell lines that we have established from metastatic, non-MYCN amplified, advanced stage neuroblastomas. These cell lines show a number of features in common, including unbalanced translocation between 11q and 17q, loss of 3p, 4p and 11q and gain of 17q. Therefore, they provide a valuable resource for the characterization of genetic pathways leading to aggressive tumor growth in non-MYCN amplified neuroblastomas.

Adrenal Gland Neoplasms↗

Breast feeding.

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Bias↗

Colour Doppler diagnosis of perigraft flow following endovascular repair of abdominal aortic aneurysm.

BACKGROUND: Endovascular repair of abdominal aortic aneurysm is a relatively new surgical technique which is less invasive than conventional open abdominal surgery but is associated with a significant specific complication of endoleak. The aim of this study was to determine the accuracy of duplex ultrasound imaging, utilising colour Doppler, as the primary method for post surgical monitoring of endovascular aneurysm repair. METHODS EXPERIMENTAL DESIGN: a case cohort study of 45 patients undergoing endovascular repair of abdominal aortic aneurysm. SETTING: angiography, CT scanning and surgery performed at Westmead Hospital, a teaching hospital of the University of Sydney; patients followed postoperatively at the Westmead Vascular Laboratory, a dedicated vascular diagnostic ultrasound facility. PATIENTS: Forty males and five females, mean age 69.1 years (range 51 to 84). INTERVENTIONS: patients underwent attempted insertion of an EVT (endovascular prosthesis) for exclusion of abdominal aortic aneurysm (mean diameter 5.3 cm; range 4.0 to 8.4 cm). Conversion to open repair was required in three cases (6.6%). An aorto-biliac graft was inserted in 28 patients, a tube graft in eight and an aorto-unilateral iliac graft with femorofemoral (or ilioilial) crossover graft in six. MEASURES: patients were followed over a period of 53 months (median follow-up time 15 months) with 106 colour Doppler scans of 39 endovascular grafts (mean of 2.9 scans per patient). RESULTS: All aneurysms decreased in diameter (range 0.1 cm to 4.3 cm, mean 0.9 cm). Abnormal flow in the residual aneurysmal sac was found in three patients. In all three cases of endoleak the colour Doppler diagnosis was supported by CT scan and confirmed on angiography. The CT scans did not provide any additional information to that obtained by colour Doppler imaging. CONCLUSIONS: Colour Doppler provides an effective means of non-invasive follow-up assessment of patients who have had endovascular repair of abdominal aortic aneurysms.

Aged↗

New equations to estimate basal metabolic rate in children aged 10-15 years.

OBJECTIVE: To develop new equations for the estimation of basal metabolic rate in children aged 10-15 years, and to evaluate the impact of including pubertal stage into the equations. DESIGN: Mixed longitudinal. SETTING: The children were recruited from schools in Oxford, and the measurements were made in the schools. SUBJECTS: 195 school children, aged 10-15 years, were recruited in three cohorts. The gender distribution of the subjects was 40% boys and 60% girls. METHODS: Basal metabolic rate (BMR) was measured, by indirect calorimetry, at 6-monthly intervals for 3 years. Anthropometric data, height, weight, body breadths and skinfold measurements (biceps, triceps, subscapular, suprailiac and medial calf) were collected on each occasion. Fat and fat-free mass was calculated from the skinfold measurements. Pubertal development was also assessed on annually by paediatricians. Pubic hair (PH) and gonad (G) development was assessed in boys and breast (B) development in girls. The girls were questioned about menarche. Stepwise multiple regression analysis was used to develop and assess new formulae for BMR that also incorporate pubertal development. RESULTS: The mean BMR measured was 5.754 (s.d. 0.933) MJ/day (138 (s.d. 22) kJ/kg body wt/day) in the boys (n = 351) and 5.476 (s.d. 0.725) MJ/day (121 (s.d. 20) kJ/kg body wt/day) in the girls (n = 554). Weight was the most important factor in developing the regression equations for the calculation of BMR in both sexes (R2 = 0.61 and 0.52 for boys and girls, respectively). Stepwise multiple regression analyses, with independent variables such as gender, weight, height, puberty stage and skinfolds, allowed several BMR regression equations to be developed. The inclusion of the menarche status in the regression equations significantly (P < 0.05) improved BMR estimation in the pre-menarche girls. Boys, pubertal stage as assessed by Pubic Hair (PH) and Gonadal Stage (G) did not contribute to a significant improvement in BMR estimation, except for 11-year-olds. CONCLUSIONS: The inclusion of pubertal stage afforded only minor improvements in the derivation of regression equations for the estimation of BMR of children aged between 10 and 15 years.

Adolescent↗

Potentiation of beta-adrenergic signaling by adenoviral-mediated gene transfer in adult rabbit ventricular myocytes.

Our laboratory has been testing the hypothesis that genetic modulation of the beta-adrenergic signaling cascade can enhance cardiac function. We have previously shown that transgenic mice with cardiac overexpression of either the human beta2-adrenergic receptor (beta2AR) or an inhibitor of the beta-adrenergic receptor kinase (betaARK), an enzyme that phosphorylates and uncouples agonist-bound receptors, have increased myocardial inotropy. We now have created recombinant adenoviruses encoding either the beta2AR (Adeno-beta2AR) or a peptide betaARK inhibitor (consisting of the carboxyl terminus of betaARK1, Adeno-betaARKct) and tested their ability to potentiate beta-adrenergic signaling in cultured adult rabbit ventricular myocytes. As assessed by radioligand binding, Adeno-beta2AR infection led to approximately 20-fold overexpression of beta-adrenergic receptors. Protein immunoblots demonstrated the presence of the Adeno-betaARKct transgene. Both transgenes significantly increased isoproterenol-stimulated cAMP as compared to myocytes infected with an adenovirus encoding beta-galactosidase (Adeno-betaGal) but did not affect the sarcolemmal adenylyl cyclase response to Forskolin or NaF. beta-Adrenergic agonist-induced desensitization was significantly inhibited in Adeno-betaARKct-infected myocytes (16+/-2%) as compared to Adeno-betaGal-infected myocytes (37+/-1%, P < 0.001). We conclude that recombinant adenoviral gene transfer of the beta2AR or an inhibitor of betaARK-mediated desensitization can potentiate beta-adrenergic signaling.

Adenoviridae↗

PCR-single-stranded confirmational polymorphism analysis for non-culture-based subtyping of meningococcal strains in clinical specimens.

Subspecific typing of clinical meningococcal strains is important in the investigation of outbreaks and for disease surveillance. Serogrouping, typing, and subtyping of strains currently require isolation of a meningococcus from one or more clinical specimens. However, the increasing widespread practice of preadmission administration of parenteral antibiotics has resulted in a decrease in the frequency of positive cultures obtained from blood and cerebrospinal fluid. Confirmation of meningococcal disease can be obtained by meningococcus-specific PCR from both cerebrospinal fluid (H. Ni et al., Lancet 340:1432-1434, 1992) and peripheral blood (J. Newcombe et al., J. Clin. Microbiol. 34:1637-1640, 1996) specimens. However, current PCR protocols do not yield epidemiologically useful typing information. We report here the use of PCR-single-stranded confirmational polymorphism (PCR-SSCP) analysis to amplify and type meningococcal DNA present in clinical specimens. PCR-SSCP analysis with the VR1 region of the Neisseria meningitidis porA gene as the target produced unique banding patterns for each serosubtype. Direct PCR-SSCP of clinical specimens can therefore provide typing data that can be used to investigate the epidemiology of clusters of cases and outbreaks and for disease surveillance in situations in which culture of patient specimens proves negative.

Bacterial Typing Techniques↗

The development of a measure of enculturation for Native American youth.

Enculturation is the process by which individuals learn about and identify with their ethnic minority culture. It is distinguished from acculturation which refers to the process by which an ethnic minority individual is assimilated into the majority culture. Three studies with Native American youths are reported that describe the development of a measure of enculturation for Native American youths. Development of a measure of enculturation provides a foundation upon which to build a body of literature that focuses on strengths in a youth's life rather than on deficits. Results of the first study (n = 120), a confirmatory factor analysis, indicated that cultural affinity, native American identity, and family involvement in traditional activities adequately represent the construct of ecnulturation. The study also provides some convergent validity for this interpretation. The second study examines factor invariance for enculturation among youths with data from over 2 years (n = 69). The factor structure was similar across time. The third study replicates the factor structure and validity analyses with a new sample (n = 42). Usefulness of the measure for assessing protective factors and stressing ethnicity over simple assessment of race categories is discussed.

Adolescent↗

Randomised comparison of chiropractic and hospital outpatient management for low back pain: results from extended follow up.

OBJECTIVE: To compare the effectiveness over three years of chiropractic and hospital outpatient management for low back pain. DESIGN: Randomised allocation of patients to chiropractic or hospital outpatient management. SETTING: Chiropractic clinics and hospital outpatient departments within reasonable travelling distance of each other in 11 centres. SUBJECTS: 741 men and women aged 18-64 years with low back pain in whom manipulation was not contraindicated. OUTCOME MEASURES: Change in total Oswestry questionnaire score and in score for pain and patient satisfaction with allocated treatment. RESULTS: According to total Oswestry scores improvement in all patients at three years was about 29% more in those treated by chiropractors than in those treated by the hospitals. The beneficial effect of chiropractic on pain was particularly clear. Those treated by chiropractors had more further treatments for back pain after the completion of trial treatment. Among both those initially referred from chiropractors and from hospitals more rated chiropractic helpful at three years than hospital management. CONCLUSIONS: At three years the results confirm the findings of an earlier report that when chiropractic or hospital therapists treat patients with low back pain as they would in day to day practice those treated by chiropractic derive more benefit and long term satisfaction than those treated by hospitals.

Adult↗

Cocaine-associated chest pain: one-year follow-up.

OBJECTIVE: To determine the one-year mortality and incidence of myocardial infarction (MI) post-hospital discharge or ED release for patients with cocaine-associated chest pain. METHODS: A prospective, observational study of an inception cohort of consecutive patients who presented to one of four municipal hospital EDs with cocaine-associated chest pain. Patients were followed for one year from the end of the enrollment period. Main outcome parameters were the one-year actuarial survival and the frequency of nonfatal MI. RESULTS: Mortality data were available for all 203 patients at a mean of 408 days. Additional clinical information was available for 185 patients (91%). There were six deaths (one-year actuarial survival 98%; 95% CI, 95-100%); none from MI. Nonfatal MI occurred in two patients (1%; 95% CI, 0-2%). Continued cocaine use was common (60%; 95% CI, 52-68%) and was associated with recurrent chest pain (75% vs 31%, p < 0.0001). No MI or death was reported for patients who claimed to have ceased cocaine use. CONCLUSIONS: Patients who presented with cocaine-associated chest pain commonly continued to use cocaine after discharge. Urgent evaluation of coronary anatomy or cardiac stress tests may not be necessary for patients for whom MI is ruled out and who do not have recurrent potentially ischemic pain. The subsequent risk for MI and death in this group appears to be low. Intervention strategies should emphasize cessation of cocaine use.

Adult↗

The Northwick Park Neck Pain Questionnaire, devised to measure neck pain and disability.

Neck pain is common in rheumatological practice. Assessment of outcome is difficult without objective measures. A neck pain questionnaire using nine five-part sections has been devised to overcome this problem. Forty-four rheumatology out-patients with neck pain were studied. Questionnaires were completed on days 0 and 3-5, and at 1 and 3 months. There was good short-term repeatability (r = 0.84, kappa = 0.62). Mean scores of each of the nine sections tended to rise with that of the pain section showing internal consistency. Questions on duration and intensity of pain were good indicators of a patient's global assessment. The questionnaire is easy for patients to complete, simple to score and provides an objective measure to evaluate outcome in patients with acute or chronic neck pain.

Adult↗

Nitroglycerin in the treatment of cocaine associated chest pain--clinical safety and efficacy.

The optimal medical regimen for the treatment of cocaine associated myocardial ischemia has not been defined. While animal and human data demonstrate the risks of beta-adrenergic blockade, studies in the cardiac catheterization laboratory suggest a beneficial role of nitroglycerin. We performed a prospective multicenter observational study to evaluate the clinical safety and efficacy of nitroglycerin in the treatment of cocaine associated chest pain at six municipal hospital centers. Of 246 patients presenting with cocaine associated chest pain, 83 patients were treated with nitroglycerin at the discretion of the treating physician. Relief of chest pain and/or adverse hemodynamic outcome were the primary endpoints. Baseline comparisons of patients treated with nitroglycerin to those not treated with nitroglycerin found that the treated patients were at higher risk of ischemic heart disease. They were older (36 years vs 32 years, p = 0.0008), more likely to have an ischemic electrocardiogram (27% vs 4%, p < 0.0001), to be admitted (94% vs 40%, p < 0.0001), and to have a discharge diagnosis of ischemic heart disease (41% vs 9%, p < 0.0001). Nitroglycerin was beneficial in 41 patients (49%; 95% CI, 38-60%): 37 patients (45%) had relief or reduction in the severity of chest pain and 4 patients (5%) had other beneficial effects. Only one patient had an adverse outcome (transient hypotension in the setting of a right ventricular infarct). Nitroglycerin is safe and possibly effective in the treatment of cocaine associated chest pain.

Adult↗

Comparative study of the T cell response to two allelic forms of a malarial vaccine candidate protein.

T cell responses to two allelic forms of the merozoite surface Ag 2 (MSA2) of Plasmodium falciparum were mapped in mice using the rMSA2 proteins, Ag 1609 which has the sequence of the FCQ27/PNG strain and Ag 1615 which has the sequence of the Indochina 1 strain. Lymph node cells of BL/10 and B10.BR mice immunized with either Ag 1609 or Ag 1615 responded to both Ag in in vitro proliferation assays. Lymph node cells of BALB/c mice did not respond. The T cell determinants recognized by the responder strains were mapped to conserved and variant regions of these Ag using overlapping synthetic peptides. The determinants recognized by each mouse strain were distinct. Marked difference in sequence between the central regions of the two rMSA2 proteins did not affect antigenic processing of the conserved N and C terminal regions. Hence lymph node cells of BL/10 mice immunized with either Ag 1615 or Ag 1609 recognized an immunodominant T cell determinant at the highly conserved N terminal end within the sequence YSNTFINNAYNMSIR (peptide 3b) and B10.BR mice similarly immunized recognized an immunodominant determinant at the highly conserved C terminal within the sequence CTDGNKENCGAATSL (peptide 23). Several peptides identified as containing immunodominant T cell determinants specific to BL/10 mice induced peptide-specific T cells in both BL/10 and B10.BR mouse strains when used as immunogens. However, the ability of the peptide-primed T cells to proliferate in response to the rMSA2 proteins was confined to BL/10 mice. An example of this was observed with peptides 3b and N (KNESKYSNTFINNAYNMSIRRSMAN). Peptide N was able to prime B10.BR and BL/10 mice for an enhanced antibody response when these mice were subsequently immunized with Ag 1615 even though Ag 1615-specific T cell proliferation was not detected in B10.BR mice primed with N. The study concluded that 1) conserved sequences such as peptide N when used in vaccines may give rise to MSA2-specific memory Th cells amenable to boosting by subsequent exposure to all parasite strains and 2) peptide priming may be a useful pathway for inducing defined memory Th cells in a wider population and for preferentially inducing T dependent over T independent responses to some malarial Ag.

Amino Acid Sequence↗