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Biomedical subjects

P O'Brien

Publications and source records attributed to P O'Brien.

At least 55 records · Page 3Linked to original sources
PubMed1996

Factors influencing outcome following radio-chemotherapy for oesophageal cancer. The Trans Tasman Radiation Oncology Group (TROG)

BACKGROUND AND PURPOSES: To define new directions, the Trans Tasman Radiation Oncology Group (TROG) has conducted a detailed analysis of its unrandomised experience with radio-chemotherapy in oesophageal cancer. METHODS AND PATIENTS: Since 1984, 373 patients with oesophageal cancer have been treated on three prospective, but unrandomised, protocols involving radiation with concurrent cisplatin and infusional fluorouracil. Centres in Australia and New Zealand have contributed patients. Reasons for case selection have been examined in detail and prognostic models have been examined in the light of biases exposed. RESULTS: Cause specific survival in 92 patients treated pre-operatively with 35 Gy, infusional fluorouracil and cisplatin was 25.5 +/- 6.0% at 5 years and similar to the 5 year expectations of 169 patients treated with 60 Gy and two courses of the same chemotherapy (23.8 +/- 4.7%). Analysis of failure in these groups suggests that local relapse precedes the development of metastases and competes as a cause for ultimate failure. Although patients treated surgically were less likely to relapse locally, survival was no better because more developed metastases. Some of the 112 patients treated "palliatively" with 30-35 Gy concurrent with chemotherapy without surgery have become long-term survivors with 5 year survival figure in this group 7.7 +/- 3.4%. Apart from variables related to disease stage and performance status at presentation, tumour site emerged as a strong predictor of outcome. Prognosis worsens the nearer the tumour is to the stomach. In addition, indications of a radiation dose response relationship emerged. CONCLUSIONS: Concurrent radio-chemotherapy protocols can improve outcome in patients fit enough to tolerate these approaches. New strategies remain necessary, however.

Adenocarcinoma↗
PubMed1996

Enhanced modulation of keratinocyte motility by transforming growth factor-alpha (TGF-alpha) relative to epidermal growth factor (EGF).

Epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha are high-affinity polypeptide ligands for the EGF receptor, which mediates their biologic activities. In this study, we directly compared the actions of both ligands in promoting keratinocyte motility. We found that normal and tumorigenic human keratinocytes responded to activation of the EGF receptor by either EGF or TGF-alpha; however, the two ligands did not elicit identical responses with regard to cell locomotion. TGF-alpha was more effective than EGF at promoting colony dispersion (cell scattering), in vitro wound closure, and single-cell migration as assessed by phagokinetic track analysis. In contrast, EGF and TGF-alpha evoked identical profiles for DNA synthesis with regard to concentration dependence and magnitude of response in normal keratinocytes and in a squamous cell carcinoma line. The overall pattern of tyrosine phosphorylation of intracellular substrates was similar when cells were stimulated with either growth factor; however, a limited number of differences in the kinetics or magnitude of protein phosphorylation were detected in subcellular fractions. These findings demonstrate that two growth factors implicated in promoting mitogenesis and locomotion may elicit divergent responses with regard to one biologic activity while retaining similar responses for other activities. This suggests that ligand-mediated mitogenic responses may not be tightly coupled to motogenic activity and further illustrates the multifunctional roles of polypeptide growth factors.

Cell Movement↗
PubMed1996

Identification of complex chromosome rearrangements in the gibbon by fluorescent in situ hybridization (FISH) of a human chromosome 2q specific microlibrary, yeast artificial chromosomes, and reciprocal chromosome painting.

Chromosome painting has revealed that the human chromosome homologs in lesser apes are often fragmented and translocated to a number of different hylobatid chromosomes. We investigated the fragmented human chromosome 2 homologs in gibbons to illustrate a new strategy in mapping regional and band-specific chromosomal homologies between species. Previous research showed that the DNA library specific to human chromosome 2 paints parts of four gibbon (lar species group) chromosomes (viz., 1, 10, 12, and 16) and yields five distinct hybridization signals (including two on gibbon chromosome 16). However, the exact segments of human chromosome 2 that were translocated to the various gibbon chromosomes could not be distinguished. To determine the origin of the human chromosome 2 signals, we hybridized a microlibrary for the long arm of human chromosome 2, as well as YACs specific for most of the major bands on this chromosome, to metaphases of the gibbon. For reciprocal chromosome painting, we hybridized flow-sorted gibbon chromosome probes to human chromosome 2. Each method added additional insights that helped clarify the shuffling of human chromosome 2 material in the highly reorganized gibbon genome. There was an excellent correspondence between these complementary techniques. YAC 958d2 identified the breakpoint between human chromosome 2 material present on gibbon chromosomes 10 and 16. The reciprocal chromosome painting permitted a more complete and regional assignment of homology between segments on various gibbon chromosomes to human chromosome 2. The results show that a combination of reciprocal chromosome painting, subregional microlibraries, and band-specific probes (such as YACs) can be used to identify homologies between species and to rapidly construct detailed comparative chromosome maps, especially when the karyotypes are highly rearranged.

Animals↗
PubMed1995

A phase III study of accelerated radiotherapy with and without carboplatin in nonsmall cell lung cancer: an interim toxicity analysis of the first 100 patients.

PURPOSE: In 1989 we initiated a multicenter randomized trial to determine if accelerated radiotherapy with or without concurrent carboplatin improves local control and survival in patients with limited nonsmall cell lung cancer. This interim analysis was performed on the first 100 patients to determine whether the toxicity of the four treatment arms is acceptable. METHODS AND MATERIALS: One hundred patients with limited nonsmall cell lung cancer have been randomized to receive one of four treatments: arm I, radiotherapy 60 Gray (Gy) in 30 fractions in 6 weeks; arm II, accelerated radiotherapy 60 Gy in 30 fractions in 3 weeks; arm III, radiotherapy as in arm I plus carboplatin 350 mg/m2 during weeks 1 and 5 of radiotherapy; arm IV, radiotherapy as in arm II plus carboplatin 350 mg/m2 during week 1. Survival was measured for the group as a whole and treatment-related toxicities in the four arms were compared. RESULTS: The estimated median survival for all 100 patients was 17.1 months with 33% estimated survival at 2 years. The major toxicities were hematologic and esophageal. Patients receiving carboplatin had more neutropenia (p < 0.0001) and thrombocytopenia (p = 0.002) than patients receiving radiotherapy alone, and this was most marked in patients on arm III. Both carboplatin and accelerated radiotherapy separately caused more severe esophagitis when compared to conventional radiotherapy alone (p = 0.011 and p = 0.0017, respectively). Esophagitis was more prolonged in patients having accelerated radiotherapy (p < 0.0001, median duration 3.2 months compared with 1.4 months for patients receiving conventional fractionation). Six patients (23%) treated on arm II have required dilatation of esophageal stricture, one dying with a laryngo-esophageal fistula. CONCLUSION: In patients receiving radiotherapy for unresectable lung cancer, overall treatment time can be halved and carboplatin administered concurrently with increased but acceptable esophageal and hematologic toxicity.

Adult↗
PubMed1995

Stereotactic radiotherapy for AVMs: the University of Toronto experience.

Since July 1989, 66 patients have received stereotactic radiosurgery for arteriovenous malformations of the brain. All cases were reviewed by our multidisciplinary group. As result of our treatment algorithms these patients underwent stereotactic radiosurgery, either as the sole therapy or as part of combined modality treatment. Using a 6 MV linear accelerator, we have usually employed doses of either 15 or 20 Gy to the edge of the lesion, ensuring that critical normal structures do not receive a dose in excess of 15 Gy. Of the initial 24 patients followed for a minimum of 2 years, 12 have complete obliteration documented by angiography; 8 have > 90% obliteration (several have deferred further angiographic follow-up which may show progression to complete obliteration); 3 have had the nidus diminish; and one has had no change. Within this cohort, one patient experienced a transient acute effect; one patient has developed a minor late effect; one suffered a fatal hemorrhage despite ongoing response to radiosurgery; one has recently undergone retreatment.

Adult↗
PubMed1995

Oxygen saturations during breast and bottle feedings in infants with congenital heart disease.

Bottle feeding is commonly advised for infants with congenital heart disease (CHD) based on the belief that breast feeding is too difficult for them. However, studies of preterm infants have shown that greater cardiorespiratory effort occurs during bottle feeding than during breast feeding. The purpose of this study is to determine if there is a relationship between feeding method (breast vs. bottle) and oxygen saturations (SaO2) in infants with CHD. In a correlational design, pulse oximetry measured SaO2 during one breast and one bottle feeding in each of 7 infants with CHD. SaO2 during breast feeding is significantly different from SaO2 during bottle feeding (F = 59.72, p < .0001). SaO2 during breast feeding is higher on average and less variable (M = 96.3%, SD = 2.2) than SaO2 during bottle feedings (M = 92.5%, SD = 6.9), indicating that there is less cardiorespiratory stress with breast feeding. None of the infants desaturated (SaO2 < 90%) during breast feedings, whereas four infants desaturated during bottle feedings.

Bottle Feeding↗
PubMed1995

Dietary shifts and implications for US agriculture.

Changes to healthier dietary patterns similar to those of traditional Mediterranean diets or those of the US government's dietary guidelines and food guide pyramid would require significant changes in American agricultural practices. The volume, mix, production, and marketing of agricultural commodities would need to be modified. Because differences between actual and recommended intakes for major food groups are quite large and affect a broad range of products, adjustments in supply and demand could overshadow past experience in dealing with such changes. New food and agriculture policies may well be needed to ease and accelerate agricultural adjustments, to improve nutritional characteristics of popular foods, and to promote desirable changes in consumers' food choices.

Agriculture↗
PubMed1995

Soluble-binding proteins for docosahexaenoic acid are present in neural retina.

PURPOSE: To determine if soluble binding proteins (BP) for fatty acids (FA), particularly docosahexaenoic acid (DHA), could be identified in the cytosol of rat and bovine retinas under in vitro and in vivo conditions. METHODS: In vitro, cytosol fractions from normal bovine and rat retinas were delipidated and incubated with [14C]-DHA with or without a number of competing fatty acids. After crosslinking bound FA to BP, the proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and radioactivity determined in each fraction. For in vivo experiments, rats received [14C]-DHA by gavage. At selected periods after ingestion, retinas were collected and cytosolic fractions were prepared from each. These were crosslinked and subjected to SDS-PAGE, and radioactivity was determined in each fraction. RESULTS: In vitro, several peaks of radioactivity (approximately 13, 20, 32, 43-45, 50, 63, and 94-105 kd) were found that exhibited [14C]-DHA binding. Relative specificity of binding was assessed by blocking of the [14C]-DHA binding with unlabeled DHA and by competition experiments with other FAs. After in vivo ingestion of [14C]-DHA, a large peak of radioactivity was observed at 43 kd by 4 hours. At 6 hours, this peak decreased and, after 24 hours, it approached baseline. CONCLUSIONS: These findings demonstrate that there is a discrete grouping of proteins in retinal cytosol capable of binding DHA and other FA. Although the identities of these proteins have yet to be determined, the group may include a member of the 12- to 15-kd group of small fatty acid binding proteins (FABP). In particular, a unique 43-kd binding peak could play a major role in the uptake, binding, or both of DHA by the retina in vivo.

Animals↗
PubMed1995

Current management of congestive heart failure in infants and children.

Although the general goals of therapy for the medical and nursing management of CHF in children have not changed in the last decade, advances have been made in understanding the unique characteristics of the neonatal heart and tailoring therapy to best support cardiac function (Table 6). In addition, strides have been made in manipulating the loading conditions of the ventricle to enhance cardiac output, which has fostered the development of new therapeutic agents and more aggressive treatment of these patients with improved outcomes. In situations in which the infant is unresponsive to therapy, surgical intervention is now done at an earlier age with good results. When surgery is not an option and the patient continues to deteriorate despite maximum medical management, mechanical support can be instituted as a bridge to transplantation.

Cardiotonic Agents↗
PubMed1994

General surgery.

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Breast Neoplasms↗
PubMed1994

Impairment, disability, and handicap in multiple sclerosis: a population-based study in Olmsted County, Minnesota.

We studied functional status of MS patients in a geographically based cohort in Olmsted County, Minnesota. The 162 definite MS patients who were alive and residing in the study area on December 1, 1991, constituted the MS prevalence disability cohort. We identified 179 cases of definite or probable MS, providing an overall sex- and age-adjusted prevalence rate of 167.5 per 100,000. Median duration of MS from onset was 15.4 years, and median age on prevalence date was 47.5 years. The Minimal Record of Disability for MS determined the degree of impairment, disability, and handicap of the entire cohort within 4 months of the prevalence date. The frequency of Expanded Disability Status Scale scores of the MS prevalence cohort showed a bimodal distribution with peaks at 1 and 6.5 (3.5 [1 to 9.5], median [range]). Approximately one-third of the cohort had marked paraparesis, paraplegia, or quadriplegia. One-fourth of all patients needed intermittent or almost constant catheterization for bladder dysfunction. Few patients (3.7%) reported severe decrease in mentation or dementia requiring supervision. Many patients (53.1%) were working full-time. Most patients (72.2%) maintained their usual financial standard without external support. There were no differences in level of impairment, disability, or handicap observed between the subgroup of 122 patients (75.3%) who are incident cases (onset of disease as residents of Olmsted County) compared with the entire prevalence cohort. This geographically based study of MS demonstrates that the functional status is more favorable than previously recognized.

Activities of Daily Living↗
PubMed1994

The generation of DNA single-strand breaks during the reduction of chromate by ascorbic acid and/or glutathione in vitro.

The potential role of iron and copper and the involvement of hydroxyl radicals in the DNA cleavage caused by chromate and glutathione (GSH) has been investigated. We have also studied the ability of chromate, on reaction with ascorbate as well as in mixed solutions of ascorbate and GSH, to cause DNA strand breaks. In both fully demetalated and conventional (i.e., metal contaminated) systems, chromate and GSH induced similar numbers of DNA strand breaks. This observation suggests that traces of iron or copper contaminating the reaction mixtures do not play a major role in the DNA cleavage caused by chromate and GSH. A series of hydroxyl radical scavengers exhibited a protective influence on the induction of DNA strand breaks. However, glucose and sucrose, both strong hydroxyl radical scavengers, showed no concentration-dependent inhibition of DNA cleavage. Competition kinetics studies yielded apparent rate constants that were not consistent with hydroxyl radicals being the species responsible for DNA strand breaks. Ascorbate in combination with chromate was also found to induce strand breaks in DNA; this damage could be attributed to reactive intermediates generated during the reduction. When mixed systems of ascorbate and GSH in the presence of chromate were investigated, there were clearly interactions between the two reductants.

Ascorbic Acid↗
PubMed1994

Chemical models important in understanding the ways in which chromate can damage DNA.

Chromate is an established human carcinogen. There have been many studies of the reactivity of chromate aimed at improving understanding of chromate toxicity. In the present paper a number of conclusions of these studies are reviewed and considered in the light of new results obtained in our laboratories. A number of hypotheses are considered; it is concluded, however, that it is impossible to reconcile the generation of strand breaks by chromate during its reduction by glutathione with any simple mechanism involving the generation of DNA lesions by free hydroxyl radicals. Kinetic, spin-trapping, and competition kinetic studies, based on a strand-breaking assay, are reported in support of this conclusion.

Animals↗