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Biomedical subjects

J Connolly

Publications and source records attributed to J Connolly.

At least 19 recordsLinked to original sources
PubMed2004

Workshop on partial breast irradiation: state of the art and the science, Bethesda, MD, December 8-10, 2002.

Breast conserving surgery followed by radiation therapy has been accepted as an alternative to mastectomy in the management of patients with early-stage breast cancer. Over the past decade there has been increasing interest in a variety of radiation techniques designed to treat only the portion of the breast deemed to be at high risk for local recurrence (partial-breast irradiation [PBI]) and to shorten the duration of treatment (accelerated partial-breast irradiation [APBI]). To consider issues regarding the equivalency of the various radiation therapy approaches and to address future needs for research, quality assurance, and training, the National Cancer Institute, Division of Cancer Treatment and Diagnosis, Radiation Research Program, hosted a Workshop on PBI in December 2002. Although 5- to 7-year outcome data on patients treated with PBI and APBI are now becoming available, many issues remain unresolved, including clinical and pathologic selection criteria, radiation dose and fractionation and how they relate to the standard fractionation for whole breast irradiation, appropriate target volume, local control within the untreated ipsilateral breast tissue, and overall survival. This Workshop report defines the issues in relation to PBI and APBI, recommends parameters for consideration in clinical trials and for reporting of results, serves to enhance dialogue among the advocates of the various radiation techniques, and emphasizes the importance of education and training in regard to results of PBI and APBI as they become emerging clinical treatments.

Breast Neoplasms↗
PubMed2004

Emergency ultrasound in the acute assessment of haemothorax.

AIMS: To evaluate thoracic ultrasound for the detection of haemothorax in patients with thoracic trauma against established investigations. METHODS: Thoracic ultrasound was performed as an extension of the standard focused assessment with sonography for trauma (FAST) protocol used at the Queen's Medical Centre for the assessment of adult patients with torso trauma. Fluid was sought in both pleural cavities using a hand portable ultrasound system by one of two non-radiologists trained in FAST. Findings were compared against subsequent investigations/procedures performed at the discretion of the attending emergency physician-supine chest radiography, intercostal drain, computed tomography, or thoracotomy. The sensitivity of the technique and the time taken to diagnosis for each investigation were recorded. RESULTS: Sixty one patients, 54 (89%) after blunt trauma, underwent thoracic ultrasound evaluation during the study. Twelve patients had a haemothorax detected by ultrasound and confirmed by computed tomography or by tube thoracostomy. Four haemothoraces detected on ultrasound were not apparent on trauma chest radiography. There were 12 true positives, 48 true negatives, no false positives, and one false negative scan. The sensitivity of ultrasound was 92% and specificity 100% with a positive predictive value of 100% and negative predictive value 98% for the detection of haemothorax after trauma. CONCLUSIONS: Emergency ultrasound of the chest performed as part of the primary survey of the traumatised patient can rapidly and accurately diagnose haemothorax and is a valuable tool to augment the immediate clinical assessment of these patients.

Acute Disease↗
PubMed2004

Prospective evaluation of non-radiologist performed emergency abdominal ultrasound for haemoperitoneum.

OBJECTIVES: To evaluate non-radiologist performed emergency ultrasound for the detection of haemoperitoneum after abdominal trauma in a British accident and emergency department. METHODS: Focused assessment with sonography for trauma (FAST) was performed during the primary survey on adult patients triaged to the resuscitation room with suspected abdominal injury over a 12 month period. All investigations were performed by one of three non-radiologists trained in FAST. The ultrasound findings were compared against the investigation of choice of the attending surgeon/accident and emergency physician. The patients were followed up for clinically significant events until hospital discharge or death. RESULTS: One hundred patients who had sustained blunt abdominal trauma, were evaluated by FAST. Nine true positive scans were detected and confirmed by computed tomography, diagnostic peritoneal lavage, or laparotomy. There was one false positive in this group, giving a sensitivity of 100%, specificity 99%, and positive predictive value of 90%. Ten patients with penetrating injuries were evaluated with a sensitivity and specificity for FAST of 33% and 86% respectively. CONCLUSIONS: Emergency torso ultrasound for the detection of haemoperitoneum can be successfully performed by trained non-radiologists within a British accident and emergency system. It is an accurate and rapid investigation for blunt trauma, but the results should be interpreted with caution in penetrating injury.

Abdominal Injuries↗
PubMed2004

Emergency surgery in patients in extremis from blunt torso injury: heroic surgery or futile care?

BACKGROUND: Trauma strikes unexpectedly, frequently in the young and fit. When trauma victims arrive in the emergency room all possible steps, including surgery, are often undertaken in an attempt to achieve a successful outcome. However, for patients presenting in extremis, with cardiac arrest or exsanguinating blunt chest injury, the results of resuscitation and emergency surgery are extremely poor. PATIENTS AND SETTING: Eight patients in extremis with a mean injury severity score of 36, presented to the resuscitation room of Queens Medical Centre during 2001. On arrival all were in extremis or cardiac arrest after significant blunt injury to the torso, and during resuscitation had a brief loss of cardiac output. They underwent emergency surgery to control haemorrhage and correct injuries in an attempt to preserve life. Seven patients died within hours of their initial presentation either in theatre or the intensive care unit and one patient survived. CONCLUSIONS: Futile care in the management of severely injured patients is a controversial concept although the literature defines four concepts of futility within surgery. At present, while there remains even the remotest possibility of survival, there remains a strong incentive to act and reports of isolated survivors from studies of trauma patients in extremis or cardiac arrest continue to emerge. This may be seen as justification for either an aggressive surgical approach or an indication that surgery is futile. In an emerging culture of guidelines regarding effectiveness of treatment, is this an area in which such guidelines can or should be applied?

Accidents, Traffic↗
PubMed2002

Cryptococcus neoformans var. gattii in the koala (Phascolarctos cinereus): serological evidence for subclinical cryptococcosis.

Cryptococcus neoformans var. gattii has been shown to have a strong association with eucalypts frequently used by koalas and, not surprisingly, it has been shown to colonize the nasal cavities of koalas. The progression from nasal colonization to tissue invasion is critical to understanding the pathogenesis of cryptococcosis in this species and provides a model for pathogenesis of cryptococcosis in other species. Cryptococcal antigenaemia was detected in twenty-eight healthy koalas from three different regions. This was interpreted as representing limited subclinical disease. One koala developed cryptococcal pneumonia 6 months after leaving the study, whereas another developed cryptococcal meningoencephalitis during the course of the study. Opportunistic necropsies on ten antigen-positive koalas resulted in discovery of small cryptococcal lesions in two (paranasal sinus and lung, respectively). Our data suggest that cryptococcal antigenaemia occurs commonly in koalas, especially in areas with a high environmental presence of C n. var. gattii. Subclinical disease appears most likely to manifest as a small focal lesion in the respiratory tract. Possible outcomes include elimination by an effective immune response, quiescence with possibility of later re-activation or direct progression to overt disease. Symptomatic and subclinical cases showed differences in levels of antigenaemia. The data presented have significant implications for koalas in captivity.

Agglutination Tests↗
PubMed2002

Prospective evaluation of handheld ultrasound in the diagnosis of blunt abdominal trauma.

OBJECTIVES: To evaluate the Sonosite 180 handheld ultrasound in the diagnosis of haemoperitoneum in blunt abdominal trauma. METHODS: Trauma ultrasound using the Focused Assessment with Sonar for Trauma (FAST) technique was performed using the Sonosite 180 handheld ultrasound during the primary survey of adult patients triaged to the resuscitation room with multiple trauma or suspected abdominal injury. The ultrasound findings were compared against the investigation of choice of the attending surgeon/accident & emergency physician--CT, DPL, laparotomy or clinical observation. RESULTS: 50 patients who had sustained blunt abdominal trauma were evaluated using FAST. Satisfactory images were obtained in 96%. There were 5 true positive scans confirmed by CT, DPL or laparotomy. There were no false negative or false investigations. The sensitivity and specificity of handheld FAST was 100%. CONCLUSIONS: Handheld ultrasound using the Sonosite 180 system can be successfully used by appropriately trained doctors as the primary investigation in the acute evaluation of blunt abdominal trauma.

Abdominal Injuries↗
PubMed2001

The interpersonal context of romantic autonomy in adolescence.

This study explored the interpersonal context of romantic autonomy in mid adolescence by examining within-relationship links with romantic intimacy and affiliation, links across relationships with mothers and friends, and individual differences due to age and gender. Two hundred and thirty adolescents in grades 9, 10 and 11 with a current romantic partner, completed self-report questionnaires assessing their relationships. The results indicated that romantic autonomy was positively linked to romantic intimacy and affiliation, although this link differed according to the duration of the romantic relationship. The results also indicated that romantic autonomy was higher among girls than boys. Finally, romantic autonomy was uniquely linked to intimacy and autonomy in both maternal and friend relationships. Overall, this study highlights the interconnection of intimacy and autonomy in romantic relationships and the interconnections across relationships.

Adolescent↗
PubMed2001

Bisphosphonate derivatized polyurethanes resist calcification.

Calcification of polyurethane cardiovascular implants is an important disease process that has the potential to compromise the long-term function of devices such as polymer heart valves and ventricular assist systems. In this study we report the successful formulation and characterization of bisphosphonate-derivatized polyurethanes, hypothesized to resist implant calcification based on the pharmacologic activity of the immobilized bisphosphonate. Fully polymerized polyurethanes (a polyurea-polyurethane and a polycarbonate polyurethane) were modified (post-polymerization) with bromoalkylation of the hard segments followed by attachment of a bisphosphonate group at the bromine site. These bisphosphonate-polyurethanes resisted calcification in rat 60 day subdermal implants compared to nonmodified control polyurethane implants, that calcify. Bisphosphonates-modified polyurethanes were also studied in circulatory implants using a pulmonary valve cusp replacement model in sheep. Polyurethane cusps modified with bisphosphonate did not calcify in 90 day implants. compared to control polyurethane cusps implants, that demonstrated nodular surface oriented calcific deposits. It is concluded that bisphosphonate modified polyurethanes resist calcification both in subdermal implants and in the circulation. This novel biomaterial approach offers great promise for long-term blood stream implantation with calcification resistance.

Animals↗
PubMed2001

Suicide, assisted suicide and euthanasia: international perspectives.

Suicide, assisted suicide and euthanasia are elusive and controversial issues worldwide. To discuss such issues from only one perspective may be limiting. Therefore, this paper was written by authors from various regions, each of whom has been asked to reflect on the issues. The countries/cultures are: Australia, China, Cuba, Ireland, India, Japan, Russia, South Africa, The Netherlands, North America (Turtle Island) and United States. Historically and today, suicide is viewed differently. Assisted suicide and euthanasia are equally seen from multifarious perspectives. Highlighting development in the Netherlands, Australia's Northern Territory and Japan (ie. the famous Yamanouchi Case), the review shows growing re-examination of the right to die. There appear, however, to be no uniform legal and ethical positions. Further debate and discussion globally is needed to avoid myopic perspectives.

China↗
PubMed2001

Localized adenovirus gene delivery using antiviral IgG complexation.

Gene therapy with viral vectors has progressed to clinical trials. However, the localization of viral vector delivery to diseased target sites remains a challenge. We tested the hypothesis that an adenoviral vector could be successfully delivered by complexation with a specific antibody that is bound to a biodegradable matrix designed for achieving localized gene transduction. We report the first successful delivery system based upon antibody immobilization of virions in a type I collagen-avidin gel using a polyclonal biotinylated IgG specific for the adenovirus hexon. In vitro stability studies demonstrated retention of viral vector activity with antibody-complexed adenovirus collagen gel preparations, in comparison to loss of vector activity from collagen gels prepared with nonspecific biotinylated IgG. Cell culture investigations using this antibody-controlled release system for adenoviral vector transduction of rat aortic smooth muscle cells (A10) demonstrated a significantly more localized reporter expression (beta-galactosidase) compared with non-antibody-complexed controls. Herpes simplex thymidine kinase (HSVtk) adenoviral vectors were immobilized on avidin-collagen gels via this antibody-complexation approach, and ganciclovir was added to rat smooth muscle cells (A10) in culture with the gels. With complexed HSVtk adenovirus, only cells either in contact with the virus-containing gel or within 50 microm were killed. By comparison, at the same adenovirus and ganciclovir dose, non-antibody-complexed HSVtk adenoviral delivery with ganciclovir resulted in the death of virtually all cells. Myocardial gene transfer studies in pigs demonstrated significantly more efficient right ventricular adenoviral GFP expression with anti-hexon antibody-complexed matrix injections, compared with direct vector injections. Thus, our results show that matrix formulations based on antibody-complexation delivery of adenovirus resulted in site-specific localization of transgene expression that enhances the efficiency of therapeutic vector strategies and provides a potent means for localization, to avoid distal side-effects. This approach has therapeutic potential as an implantable preparation that through the means of antibody-complexation, can localize and optimize viral vector gene therapy.

Adenoviridae↗
PubMed2001

In vitro microleakage of luting cements and crown foundation material.

STATEMENT OF PROBLEM: Microleakage is a concern for the long-term prognosis of a cemented crown and foundation. PURPOSE: The aims of this investigation were, first, to evaluate microleakage of zinc phosphate cement and resin-reinforced glass ionomer cement under ideal (dry) versus contaminated (wet) conditions, and second, to compare 3 foundations under both ideal and contaminated conditions. MATERIAL AND METHODS: One hundred forty extracted molar teeth were cleaned and mounted. Tooth preparations for complete veneer cast crowns were completed with a chamfer finish line. A mesial surface class II cavity preparation 4 mm wide buccolingually and 2 mm deep was made in each tooth. Seven restorative groups were formed: amalgam/cavity varnish, amalgam/dentinal bonding agent, and composite/dentinal bonding agent, each with dry and contaminated groups, and a seventh group of class II cavity preparations without foundations. Finish lines for crown margins were refined 1.5 mm gingival to the restoration. Artificial crowns were cast in type III gold. Treatment groups were divided into 4 cement groups: dry and contaminated zinc phosphate cement and dry and contaminated resin-reinforced glass ionomer cement. The specimens were thermocycled and immersed in erythrosine B solution for 24 hours. Subsequently, they were rinsed, and their coronal portions were embedded in clear resin. Teeth were sectioned mesiodistally, and standard photomicrographs were made. The microleakage of each restoration and crown was measured. RESULTS: The least foundation microleakage was recorded for amalgam/dentinal bonding agents (ideal group) and composite/dentinal bonding agents (ideal group). The most microleakage was observed within the group without a foundation. In cement groups, the control and experiment sides were evaluated separately but displayed the same order of finding. The least leakage was recorded with resin-reinforced glass ionomer cement (ideal group); the most microleakage was noted with zinc phosphate cement (ideal group). An interaction was demonstrated on the experimental side between cements and the foundations (P=.0001). CONCLUSION: Within the experimental conditions of this study, less microleakage was recorded with resin-reinforced glass ionomer cement (ideal or contaminated) than with zinc phosphate cement (ideal or contaminated). There also was less microleakage evident with a foundation of silver amalgam or composite when a dentinal bonding agent was used under ideal conditions.

Analysis of Variance↗
PubMed2001

The contribution of early traumatic events to schizophrenia in some patients: a traumagenic neurodevelopmental model.

The current diathesis-stress model of schizophrenia proposes that a genetic deficit creates a predisposing vulnerability in the form of oversenstivity to stress. This model positions all psychosocial events on the stress side of the diathesis-stress equation. As an example of hypotheses that emerge when consideration is given to repositioning adverse life events as potential contributors to the diathesis, this article examines one possible explanation for the high prevalence of child abuse found in adults diagnosed schizophrenic. A traumagenic neurodevelopmental (TN) model of schizophrenia is presented, documenting the similarities between the effects of traumatic events on the developing brain and the biological abnormalities found in persons diagnosed with schizophrenia, including overreactivity of the hypothalamic-pituitary-adrenal (HPA) axis; dopamine, norepinephrine, and serotonin abnormalities; and structural changes to the brain such as hippocampal damage, cerebral atrophy, ventricular enlargement, and reversed cerebral asymmetry. The TN model offers potential explanations for other findings in schizophrenia research beyond oversensitivity to stress, including cognitive impairment, pathways to positive and negative symptoms, and the relationship between psychotic and dissociative symptomatology. It is recommended that clinicians and researchers explore the presence of early adverse life events in adults with psychotic symptoms in order to ensure comprehensive formulations and appropriate treatment plans, and to further investigate the hypotheses generated by the TN model.

Adult↗
PubMed2001

Eating problems and the observed quality of mother-daughter interactions among girls with type 1 diabetes.

This study examined how eating problems are linked to autonomy and intimacy in the observed interactions of 88 diabetic girls (M = 14.9 years) and their mothers. On the basis of self-reported symptoms, teens were classified as having no eating problems (n = 40), mild eating problems (n = 30), and frequent eating problems (n = 18). Mothers and daughters participated in 2 videotaped problem-solving tasks (1 diabetes related and I a general parent-teen issue) that were rated with a macroanalytic coding system (Autonomy and Intimacy Rating System). Compared with interactions among mothers and daughters with no eating problems, interactions among mothers and daughters with eating problems simultaneously constrained the expression of autonomy and intimacy. Findings support clinical theory that links eating problems to emotional misattunement in the mother-daughter relationship, which is postulated to interfere with the teen's capacity for individuation.

Adolescent↗
PubMed2000

Cell cycle arrest and apoptosis of melanoma cells by docosahexaenoic acid: association with decreased pRb phosphorylation.

The incidence of cutaneous malignant melanoma is undergoing a dramatic increase in persons with light-color skin in all parts of the world. The prognosis for individuals with advanced disease is dismal due to the lack of effective treatment options. Thus, there is a need for new approaches to control tumor progression. Epidemiological, experimental, and mechanistic data implicate omega-6 polyunsaturated fatty acids (PUFAs) as stimulators and long-chain omega-3 PUFAs as inhibitors of development and progression of a range of human cancers, including melanoma. The aim of this study was to assess the mechanisms by which docosahexaenoic acid (DHA), an omega-3 PUFA, affects human melanoma cells. Exponentially growing melanoma cell lines were exposed in vitro to DHA and then assessed for (a) inhibition of cell growth; (b) expression of cyclins and cyclin-dependent kinase inhibitors in individual cells by flow cytometry and immunocytochemistry using specific monoclonal antibodies to cyclin D1, cyclin E, p21WAF1/CIP1, or p27(KIP1); and (c) expression of total pRb(T) independent of phosphorylation state and hypophosphorylated pRb(P-) in fixed cells by flow cytometry and immunocytochemistry using specific monoclonal antibodies to pRb(T) or pRb(P-), respectively. After treatment with increasing concentrations of DHA, cell growth in a majority of melanoma cell lines (7 of 12) was inhibited, whereas in 5 of 12 cell lines, cell growth was minimally affected. Two melanoma cell lines were examined in detail, one resistant (SK-Mel-29) and one sensitive (SK-Mel-110) to the inhibitory activity of DHA. SK-Mel-29 cells were unaffected by treatment with up to 2 microg/ml DHA whether grown in the absence or presence of 1% fetal bovine serum (FBS). No appreciable change was observed in cell growth, cell cycle distribution, the status of pRb phosphorylation, cyclin D1 expression, or the levels of the cyclin-dependent kinase inhibitors p21 and p27. In contrast, SK-Mel-110 cell growth was inhibited by DHA with the cells accumulating either in G1 or S phase: 0% in SK-Mel-29 versus 13.3 or 41.2% in SK-Mel-110 in the absence or presence of FBS, respectively. In the absence of serum, considerable death occurred by apoptosis. In addition, DHA treatment resulted in increasing numbers of SK-Mel-110 cells (from 12 to >40%) expressing hypophosphorylated pRb, whereas the levels of cyclin D1 and p21 changed little. Expression of p27 in these cells increased >2.5 times when grown in the absence of FBS but not in the presence of 1% FBS. Thus, we show for the first time that DHA inhibits the growth of cultured metastatic melanoma cells. Furthermore, growth inhibition correlates with a quantitative increase in hypophosphorylated pRb in the representative sensitive melanoma cell line SK-Mel-110. Although multiple factors influence pRb phosphorylation, it appears that both cyclin D1 and p21 expression do not change in the presence of DHA, although p27 was strikingly increased in SK-Mel-110 cells in the absence of FBS. The fact that pRb became hypophosphorylated after exposure to DHA suggests a cross-talk mechanism between fatty acid metabolism and the pRb pathway. Determining the mechanism by which PUFAs can inhibit melanoma growth will be an important first step in the rational use of PUFAs as antitumor agents.

Animals↗