PubMed Health⌕ Search

Biomedical subjects

S O'Neill

Publications and source records attributed to S O'Neill.

At least 19 recordsLinked to original sources
PubMed2003

Quality assessment of genetic markers used for therapy stratification.

PURPOSE: Therapy stratification based on genetic markers is becoming increasingly important, which makes commitment to the highest possible reliability of the involved markers mandatory. In neuroblastic tumors, amplification of the MYCN gene is an unequivocal marker that indicates aggressive tumor behavior and is consequently used for therapy stratification. To guarantee reliable and standardized quality of genetic features, a quality-assessment study was initiated by the European Neuroblastoma Quality Assessment (ENQUA; connected to International Society of Pediatric Oncology) Group. MATERIALS AND METHODS: One hundred thirty-seven coded specimens from 17 tumors were analyzed in 11 European national/regional reference laboratories using molecular techniques, in situ hybridization, and flow and image cytometry. Tumor samples with divergent results were re-evaluated. RESULTS: Three hundred fifty-two investigations were performed, which resulted in 23 divergent findings, 17 of which were judged as errors after re-evaluation. MYCN analyses determined by Southern blot and in situ hybridization led to 3.7% and 4% of errors, respectively. Tumor cell content was not indicated in 32% of the samples, and 11% of seemingly correct MYCN results were based on the investigation of normal cells (eg, Schwann cells). Thirty-eight investigations were considered nonassessable. CONCLUSION: This study demonstrated the importance of revealing the difficulties and limitations for each technique and problems in interpreting results, which are crucial for therapeutic decisions. Moreover, it led to the formulation of guidelines that are applicable to all kinds of tumors and that contain the standardization of techniques, including the exact determination of the tumor cell content. Finally, the group has developed a common terminology for molecular-genetic results.

Biomarkers, Tumor↗
PubMed2002

Assessing the dietetic needs of different patient groups receiving enteral tube feeding in primary care.

AIM: To examine the nature of all contacts between adult tube-fed patients and the dietetic service and to refine the current dietetic protocols to reflect the findings of the study with a view to improving patient care. METHODS: All adult patients referred to the Community Nutrition and Dietetic Service within a 6-month period were included in the study. Using a proforma developed from a retrospective case-note analysis, data were collected on the complications that prompted more frequent contacts than the department protocol. Data were analysed using the Statistical Package for the Social Sciences. RESULTS: The most common indication for home enteral feeding in this group of adult patients was a swallowing disorder resulting from a cerebrovascular accident (59.5%) followed by cancer (21.5%). There was a trend for cancer patients to need more intervention compared with those patients with other medical conditions. A significant difference was observed in the total contacts and telephone calls given to those patients in there own homes (P=0.019) and there was a trend towards more domicilary visits with this group. CONCLUSIONS: The department protocols have been revised to include a planned review within 2-6 weeks of initial dietetic assessment in the community for those patients who were identified to have the greatest need. More intensive dietetic monitoring has clear implications for dietetic services in the community.

Adolescent↗
PubMed2002

Sports medicine and the accident and emergency medicine specialist.

BACKGROUND: Sport and exercise related injuries are responsible for about 5% of the workload in the accident and emergency (A&E) department, yet training in sports medicine is not a compulsory part of the curriculum for Higher Specialist Training. AIM: To determine how A&E medicine consultants and specialist trainees view their role and skill requirements in relation to sports medicine. METHOD: A modified Delphi study, consisting of two rounds of a postal questionnaire. Participants were invited to rate the importance of statements relating to the role and training of the A&E specialist in relation to sports injuries (six statements) and the need for knowledge and understanding of defined skills of importance in sports medicine (16 statements). VALUE OF RESEARCH: This provides a consensus of opinion on issues in sport and exercise medicine that have educational implications for A&E specialists, and should be considered in the curriculum for Higher Specialist Training. There is also the potential for improving the health care provision of A&E departments, to the exercising and sporting population.

Athletic Injuries↗
PubMed2001

Comprehensive genetic and histopathologic study reveals three types of neuroblastoma tumors.

PURPOSE: To determine the relationship between multiple genetic features, tumor morphology, and prognosis in neuroblastoma. PATIENTS AND METHODS: The genetic alterations and morphologic features that underpin three histopathologic risk classifications were analyzed in 108 neuroblastoma patients. Tumors were subdivided into four groups based on the three most frequent and prognostically significant genetic alterations (17q gain, 1p deletion, and MYCN amplification), and all other genetic, morphologic, and clinical data were analyzed with respect to these groups. RESULTS: Our analyses identify three nonoverlapping tumor types with distinct genetic and morphologic features, defined here as types 1, 2, and 3. Type 1 tumors show none of the three significant genetic alterations and have good prognosis. Both type 2 (17q gain only or 17q gain and 1p del) and type 3 (17q gain, 1p del, and MYCN amplification) tumors progress. However, these tumor types are distinguished clinically by having significantly different median age at diagnosis and median progression-free survival (PFS). Multivariate analysis indicates that 17q gain is the only independent prognostic factor among all genetic, histopathologic, and clinical factors analyzed. Among histopathologic risk systems, the International Neuroblastoma Pathology Classification was the best predictor of PFS. CONCLUSION: Our results indicate that specific combinations of genetic changes in neuroblastoma tumors contribute to distinct morphologic and clinical features. Furthermore, the identification of two genetically and morphologically distinct types of progressing tumors suggests that possibilities for different therapeutic regimens should be investigated.

Adolescent↗
PubMed2001

Low sodium inotropy is accompanied by diastolic Ca2+ gain and systolic loss in isolated guinea-pig ventricular myocytes.

We measured sarcolemmal Ca2+ fluxes responsible for the positive inotropic effects of solutions with reduced Na+ concentration in voltage-clamped guinea-pig ventricular myocytes; intracellular Ca2+ concentration ([Ca2+]i) was measured with Indo-1. Reduction of external Na+ concentration by 50 % (to 67 mM) produced an increase in systolic [Ca2+]i accompanied by a decrease in Ca2+ entry via the L-type Ca2+ current. With reduced Na+ concentration, there was an initial decrease in the Na+-Ca2+ exchange current on repolarization followed by an increase to greater than control. We attribute this initial decrease to a decrease in the Na+ gradient and the subsequent increase to a fall in intracellular Na+ concentration and increase in systolic [Ca2+]i. The decreased L-type Ca2+ current and increased Ca2+ efflux on Na+-Ca2+ exchange resulted in a calculated systolic loss of Ca2+. The calculated systolic loss of Ca2+ was accompanied by a measured increase in sarcoplasmic reticulum (SR) Ca2+ content. Reduction of the external Na+ concentration also produced an outward shift of holding current which was blocked by Ni2+. This is taken to represent Ca2+ influx via Na+-Ca2+ exchange. When diastolic influx is taken into account, the observed gain in SR Ca2+ content can be predicted. The measurements show that, in reduced Na+, much of the entry of Ca2+ into the cell occurs during diastole (via Na+-Ca2+ exchange) rather than in systole (via the L-type Ca2+ current).

Animals↗
PubMed2001

17q gain in neuroblastoma predicts adverse clinical outcome. U.K. Cancer Cytogenetics Group and the U.K. Children's Cancer Study Group.

BACKGROUND: It is now recognized that gain of chromosome 17 material is the most frequent genetic abnormality of neuroblastoma cells. Several studies have linked 17q gain with known adverse prognostic factors: patient age >1 year, advanced stage disease, deletion of chromosome arm 1 p, and amplification of the MYCN oncogene. We sought to further investigate the clinical and prognostic associations of chromosome 17 status in relation to other well-established predictive factors. PROCEDURE: In a collaborative study by UK cytogenetics centres, we compiled a series of 104 neuroblastoma tumours for which the status of chromosome 17 was confidently defined by cytogenetics, metaphase or interphase FISH, or CGH analysis. The results were correlated with data on 1p and MYCN, and with centrally collated clinical and survival information. RESULTS: Gain of 17q (i.e., unbalanced gain of segment 17q21-qter) was found in 66.3% of tumours, while 33.7% showed a '17q normal' status (i.e., no gain at all, or gain of whole chromosome 17 relative to ploidy). Gain of 17q was strongly associated with advanced stage disease, patient age >1 year, 1p deletion, and MYCN amplification (all P< 0.01). In univariate analysis, 17q gain was a significant predictor of adverse outcome (projected 5 year relapse-free survival 15.6% compared to 75.2% in cases lacking this feature in tumour cells; (P < 0.0001). In multivariate analysis, 17q gain was more strongly associated with adverse outcome than was either stage (Stage 4 vs other combined) or 1p status. CONCLUSION: We conclude that gain of chromosome segment 17q21-qter is of great biological and clinical importance in neuroblastoma, and that its detection at diagnosis should be a priority.

Blotting, Southern↗
PubMed2001

A Val193Met mutation in GPIIIa results in a GPIIb/IIIa receptor with a constitutively high affinity for a small ligand.

We have identified a patient designated as (GTa) with Glanzmann's Thrombasthenia (GT) diagnosed on the basis of a prolonged bleeding time and failure of the patient's platelets to aggregate. The number of glycoprotein (GP)IIb/IIIa receptors on the platelet surface was 37% of normal and those receptors displayed a defect in soluble fibrinogen binding. Nevertheless, GTa platelets showed increased adhesion to solid-phase fibrinogen and binding affinity for the RGD-mimetic (3)H-SC52012, a non-peptide GPIIb/IIIa antagonist. Dithiothreitol (DTT) and ADP enhanced the affinity for [(3)H]-SC52012 in normal platelets, but had little effect in GTa platelets. These findings suggested that GTa platelets were locked in an altered affinity state. Genetic analysis showed that GTa was a compound heterozygote for the GPIIIa gene. One allele showed a deletion at the 3' end of exon 3 resulting in a premature stop codon. The second GPIIIa allele had a G to A transition at nucleotide 577, resulting in a Val193Met substitution. HEK 293T cells transfected with mutant GPIIb/IIIaV193M bound [(3)H]-SC52012 with a higher affinity than wild-type GPIIb/IIIa, and this was not increased by DTT. The mutant receptor distinguishes between platelet adhesion and aggregation, and demonstrates the phenotype that may be expected when platelet aggregation alone is inhibited.

Adenosine Diphosphate↗
PubMed2001

Genetic insights into the neurodevelopmental hypothesis of schizophrenia.

The original neurodevelopmental hypothesis of schizophrenia presented by D.R. Weinberger in 1987 focused on pathogenesis and did not address etiology. Available evidence indicates that genetic factors are the principal cause of schizophrenia. It is imperative that any pathogenetic model for schizophrenia takes into account what is now known about genetic mechanisms of illness. Recent advances in molecular genetics can provide insights into the neurodevelopmental expression of the illness and what future genetic discoveries are likely to contribute to our understanding of schizophrenia. In this article, we propose a genetic model of etiopathogenesis that is consistent both with a modified neurodevelopmental hypothesis and our current knowledge about schizophrenia and molecular genetics.

Chromosome Deletion↗
PubMed2001

Alpha1-antitrypsin deficiency: biological answers to clinical questions.

Alpha1-antitrypsin (alpha1AT) deficiency is a common lethal hereditary disorder of white persons of European descent. The condition is characterized by reduced serum levels of alpha1AT, a 52-kDa glycoprotein synthesized chiefly in the liver and, to a lesser extent, by macrophages and neutrophils. Alpha1AT acts as an antiprotease and is the physiological inhibitor of neutrophil serine proteases such as neutrophil elastase cathepsin G and proteinase 3. The clinical manifestations of alpha1AT deficiency occur chiefly in the lung, with a high risk of emphysema occurring by the third or fourth decade of life. Cigarette smoking accelerates the development of emphysema in persons with alpha1AT deficiency. There is also an increased risk of liver disease in alpha1AT deficiency, which occurs mostly in childhood. In this review, we will define further the diagnosis of alpha1AT deficiency and its clinical manifestations and describe the therapeutic strategies that are currently being developed to treat the hepatic and pulmonary disease associated with this condition.

Adult↗
PubMed2001

Genetic counselling for schizophrenia in the era of molecular genetics.

OBJECTIVE: To review the role of genetic counselling for individuals with psychiatric illnesses. METHOD: Using schizophrenia as an example and including updated information about a genetic subtype (22q deletion syndrome), we discuss the value of the genetic counselling process in psychiatry, with support from the literature and our clinical experience. RESULTS: Genetic counselling, the process through which knowledge about the genetics of illnesses is shared, provides information on the inheritance of illnesses and their recurrence risks; addresses the concerns of patients, their families, and their health care providers; and supports patients and their families dealing with these illnesses. For comprehensive medical management, this service should be available to all individuals with schizophrenia and their families. CONCLUSIONS: New findings in the genetics of psychiatric illness may have important clinical implications for patients and their families.

Chromosome Deletion↗
PubMed2001

Improved asthma control with budesonide/formoterol in a single inhaler, compared with budesonide alone.

Budesonide/formoterol in a single inhaler was compared with budesonide alone, and with concurrent administration of budesonide and formoterol from separate inhalers, in patients with asthma, not controlled with inhaled glucocorticosteroids alone. In this 12-week, double-blind, randomized, double-dummy study, 362 adult asthmatics (forced expiratory volume in one second 73.8% of predicted, inhaled glucocorticosteroid dose 960 microg x day(-1)) received single inhaler budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg, two inhalations b.i.d., or corresponding treatment with budesonide, or budesonide plus formoterol via separate inhalers. There was a greater increase in morning peak expiratory flow (PEF) with single-inhaler (35.7 L x min(-1)) and separate-inhaler (32.0 L x min(-1)) budesonide and formoterol, compared with budesonide alone (0.2 L x min(-1); p<0.001, both comparisons); the effect was apparent after 1 day (p<0.001 versus budesonide, both comparisons). Similarly, evening PEF, use of rescue medication, total asthma symptom scores and percentage of symptom-free days improved more with both single inhaler and separate inhaler therapy than with budesonide alone, as did asthma control days (approximately 15% more, p<0.001 versus budesonide, both comparisons, with a marked increase in the first week). All treatments were well tolerated and the adverse event profile was similar in all three treatment groups. It is concluded that single inhaler therapy with budesonide and formoterol is a clinically effective and well-tolerated treatment for patients with asthma that is not fully controlled by inhaled glucocorticosteroids alone.

Administration, Inhalation↗
PubMed2001

Nitinol stent insertion for post-pneumonectomy syndrome.

Post-pneumonectomy syndrome is an unusual condition, that can occur a variable period of time after a patient has had a pneumonectomy. Management of this syndrome has been described using a number of different techniques, often with considerable mortality. We present a case report where this condition was treated successfully by insertion of an expandable Nitinol stent. This is the first time this technique has been described to treat this condition, and we feel it may be the procedure of choice in managing these patients.

Alloys↗
PubMed2001

The psychotherapy of a male anorectic.

The author describes the way in which a male anorexic patient came to be understood in once-weekly psychotherapy. The findings are similar to recent psychoanalytic ones about female anorectics, but add that he was preoccupied with display and that there was an erotised transference in the oral mode. Of two major themes, the first was a food obsession; the food was felt concretely to be the mother as in a symbolic equation, and the conflict about eating represented a wish for and fear of fusion with her. The second major theme concerned exhibition; the self, as seen in two screen memories, was felt to be uncomfortably on show. Meanwhile the patient was preoccupied with a self-displaying maternal object, which was prominent in the transference. This perception of the object served as a defence against envy, although the defensive aspect may have been added to by an actual experience of a mother who functioned operatively, giving food rather than loving attention. The patient employed primary-process thinking defensively against self-object differentiation, which would have excited further awareness both of envy and of the real deficiencies of his primary objects. The author raises the possibility that the anorexia functioned as a perversion, binding and organising the core complex about fusion.

Adult↗
PubMed2001

Antioxidant prevention of Heinz body formation and oxidative injury in cats.

OBJECTIVE: To determine the effectiveness of 3 antioxidants in preventing Heinz body anemia in cats. DESIGN: Prospective study. ANIMALS: 44 specific-pathogen-free healthy cats. PROCEDURE: Cats were housed individually, divided randomly into 4 groups, and given the following orally every 12 hours: empty gelcaps (control cats), N-acetylcysteine (NAC, 100 mg/kg of body weight), vitamin E (d,l-alpha-tocopherol; 400 IU), or ascorbate (250 mg). After 2 weeks, Heinz bodies were induced by dietary onion powder (OP; 1% or 3% of dry matter) or propylene glycol (PG, 8% wt/vol in drinking water) for an additional 3 weeks. Intake of treated water or food was recorded daily. Body weight, PCV, Heinz body and reticulocyte percentages, reduced glutathione concentration, and total antioxidant status were measured twice weekly in all cats. RESULTS: Heinz body percentage and degree of anemia did not differ significantly among cats receiving antioxidants and control cats except in cats that ingested water containing PG, in which antioxidant supplementation was associated with a decrease in water intake. Of cats that were fed a diet that contained OP, cats that received NAC had significantly higher reduced glutathione concentrations, compared with other cats in the experiment. Total antioxidant status did not consistently correlate with antioxidant supplementation or type of oxidant administered (ie, OP or PG). CONCLUSIONS AND CLINICAL RELEVANCE: Although the effect of antioxidant supplementation on Heinz body anemia in cats was minimal, antioxidants may have subclinical biochemical effects such as GSH sparing that may be important against milder forms of oxidative stress.

Acetylcysteine↗
PubMed2001

MYCN amplification and 17q in neuroblastoma: evidence for structural association.

MYCN oncogene amplification in neuroblastoma is statistically associated with gain of chromosome segment 17q21-qter. In neuroblastoma cell lines and primary tumors with MYCN amplification in the form of homogeneously staining regions (hsrs), juxtaposition of chromosome 17 material with MYCN sequences has occasionally been reported, raising the possibility of a physical affinity between MYCN and chromosome arm 17q. We used FISH to test for association between chromosome 17 segments and MYCN in eight neuroblastoma cell lines and two neuroblastoma primary tumors known to include hsrs. Evidence of an association was found in the chromosomes of both primary tumors; in one, a MYCN hsr was inserted into a structurally abnormal chromosome 17, in the other, an hsr in 16p was shown to be flanked by 17 material. In cell line NCG, hsrs in 4q and 16p were flanked by 17q material. These observations confirm the juxtaposition of 17q material with MYCN sequences in some neuroblastomas, and imply that there may be a physical or functional relationship between these two features in MYCN amplified neuroblastoma.

Child, Preschool↗
PubMed2001

Daughters and mothers exercising together (DAMET): a 12-week pilot project designed to improve physical self-perception and increase recreational physical activity.

This paper presents the results of a 12-week single-sex, family-based physical activity intervention grounded in Social Cognitive Theory. Mother/daughter pairs and triads (n = 20) attended physical activity and classroom sessions twice weekly. Physiological data (VO2peak, height, and weight), psychological data (physical self-perception profile subscale scores), information about physical activity participation (PAP, d x wk(-1)) and qualitative impressions (QI) of the program were collected pre- and post-intervention. PAP and QI were also collected 6-months after completing the intervention. Although no significant increases in physical activity were reported, significant improvements in perceived sport competence, physical condition, and strength and muscularity were reported over time. The social cognitive theory, as used to plan this physical activity intervention, offered a promising theoretical perspective for facilitating improved physical self-perception in adolescent girls and their mothers.

Adolescent↗