Doctors who smoke. Doctors should advise but do not have to lead by example.
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Humans↗
Biomedical subjects
P O'Brien
Publications and source records attributed to P O'Brien.
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↗
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↗
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↗
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↗
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↗
Detection of alloimmune thrombocytopenia as cause of isolated hydrocephalus by fetal blood sampling.
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Adult↗
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↗
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↗
Rabbit haemorrhagic disease virus.
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Animals↗
Radiation and carboplatin combined-modality therapy in non-small cell lung cancer.
Previously untreated patients with stages I to IV, N0-3, M0 unresectable non-small cell lung cancer were randomized to arm I (conventional radiotherapy [RT], 60 Gy in 30 fractions over 6 weeks), arm II (accelerated RT, 60 Gy in 30 fractions over 3 weeks), arm III (conventional RT, as in arm I, plus carboplatin 70 mg/m2/d on days 1 to 5 during treatment weeks 1 and 5), or arm IV (accelerated RT, as in arm II, plus carboplatin 70 mg/m2/d on days 1 to 5 of week 1 only). An intensive analysis of toxicity in the first 92 patients entered revealed significantly more neutropenia (P < .0001) and thrombocytopenia (P = .004) in the combined-modality arms. Esophagitis was worse on arms II, III, and IV, but was more prolonged in the accelerated RT arms. Overall, however, the treatment on all study arms was well tolerated.
Antineoplastic Combined Chemotherapy Protocols↗
Chronic hypoxemia in children with cyanotic heart disease.
Hypoxemia, visible as cyanosis, is present in infants and children with congenital cardiac defects that result in arterial desaturation. Although many of these defects can be surgically repaired, some children remain cyanotic. Chronic cyanosis causes adaptive changes such as polycythemia and potentially damaging changes in other organ systems. This article reviews the assessment and management of patients with cyanotic congenital heart disease. The physiologic consequences and associated medical problems of chronic cyanosis are highlighted. Nursing implications in caring for cyanotic children and young adults are discussed.
Child↗
Generation of substance P carbamate in neutral aqueous solution. Relevance to inflammatory joint diseases.
High-field proton (1H) nuclear magnetic resonance (NMR) spectroscopy has been employed to evaluate the formation of substance P carbamate in aqueous solution. Equilibration of substance P with physiologically relevant concentrations of bicarbonate (2.50 x 10(-2) mol.dm-3) at pH 7.00 generated a new multiplet signal centred at 4.13 ppm in its NMR spectrum, characteristic of the alpha-proton of peptide carbamate species. High-field 1H NMR spectroscopy also demonstrated that the model dipeptide, Arg-Gly, formed a carbamate in neutral aqueous solutions containing 2.50 x 10(-2) mol.dm-3 HCO3-. The physiological significance of these results is discussed in view of the central roles of vasoactive neuropeptides in human joint diseases and the hypercapnic environment of the inflamed rheumatoid joint.
Arthritis, Rheumatoid↗
Recovery of contractile function of postischemic, reperfused myocardium: influence of 2,3-butanedione-2-monoxime.
Inhibition of mechanical activity during ischemia could improve recovery of stunned myocardium. In this study, the effect of 2,3-butanedione-2-monoxime (BDM), an agent that disrupts excitation-contraction coupling, on the time course of recovery of contractile function of postischemic reperfused myocardium was studied in open-chest anesthetized dogs. Ischemia was produced by occluding the left anterior descending coronary artery (LAD) for 15 mins. In separate experimental groups, during the occlusion period, 6 ml of either 100 mM BDM or drug vehicle (0.9% normal saline) was infused into the distal perfusion bed subjected to occlusion. Regional myocardial function (percentages of segment shortening % SS) was assessed by sonomicrometry. LAD occlusion resulted in similar degrees of dyskinesia in both experimental groups. Subsequent recovery of contractile function during reperfusion was evaluated for 3 h. In control experiments, segment shortening remained significantly (p < 0.05) decreased throughout the reperfusion period, returning to only 36.1 +/- 9.2% of the preocclusion value at 3 h postreperfusion. In BDM experiments, regional contractile function returned to 72.4 +/- 11.3% of the preocclusion value at 1 h of reperfusion. Rapid recovery was sustained throughout reperfusion. Regional stroke work area (RSWA) also demonstrated rapid sustained recovery of function after treatment with BDM. RSWA was significantly greater in BDM experiments as compared with control experiments at all times during the reperfusion period. These results demonstrate that selective intracoronary (i.c.) administration of BDM during ischemia markedly enhances postischemic recovery of contractile function. The underlying mechanism for this action may involve modulation of several aspects of impaired cellular function in postischemic tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Regional redistribution of myocardial perfusion by UL-FS 49, a selective bradycardic agent.
The effects of UL-FS 49, a specific bradycardic agent, on systemic hemodynamics, regional myocardial function (sonomicrometry, percentage of segment shortening), and regional coronary blood flow (radioactive microspheres) were studied in open-chest, anesthetized dogs with severe left circumflex coronary artery (LCX) stenosis. UL-FS 49 was administered as two sequential bolus injections of 0.25 mg/kg. Heart rate decreased from 149 +/- 13 beats/min to 102 +/- 6 and 77 +/- 4 beats/min after 0.25 and 0.5 mg/kg cumulative doses of UL-FS 49, respectively. The reduction in heart rate was not associated with any significant change in left ventricular pressure or mean arterial pressure, left ventricular dp/dt, or coronary vascular resistance. Similarly no hemodynamic changes occurred with atrial pacing to the initial heart rate. Application of an LCX stenosis of sufficient severity to produce a 50% reduction in mean LCX blood flow (44 +/- 4 to 22 +/- 2 ml/min) resulted in a significant reduction in the percentage of segment shortening in the ischemic zone (9.8 +/- 1.6% to 6.5 +/- 1.1%). The percentage of segment shortening in the ischemic zone progressively improved to 8.4 +/- 1.2% and 9.4 +/- 0.5% after 0.25 and 0.5 mg/kg UL-FS 49, respectively. Subepicardial perfusion in the ischemic zone was decreased and subendocardial perfusion was increased after administration of UL-FS 49. Consequently the ischemic zone endocardial/epicardial ratio increased from 0.43 +/- 0.08 to 1.12 +/- 0.22 and 1.48 +/- 0.32 with low and high doses of UL-FS 49.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Defining conditions for the efficient in vitro cross-linking of proteins to DNA by chromium(III) compounds.
The formation of cross-links between bovine serum albumin and DNA in the presence of chromium(III) chloride was found to be highly pH dependent. In vitro, such lesions were only formed at acidic values of pH, but were not detected at neutral pH. Complexes of chromium(III) and GSH/GSSG similarly failed to induce DNA-protein cross-links at physiological values of pH. Our findings indicate that the cross-links generated in vitro at acidic pH may not be directly relevant to the observed formation of such lesions in cultured cells and that a physiologically relevant in vitro model for the efficient cross-linking of proteins to DNA has yet to be devised.
Bacteriophages↗
Surgical management of late right ventricular failure after Mustard or Senning repair.
BACKGROUND: Information on surgical management and outcome in patients who develop symptomatic right ventricular failure after prior Mustard or Senning operations is limited. METHODS AND RESULTS: From March 1987 to March 1991, 10 patients 3.6-23.5 years old (median, 7.0 years) with transposition of the great arteries and prior Mustard (six patients) or Senning (four patients) repairs (performed at ages 2 months to 5 years; median, 6 months) underwent surgical intervention for symptomatic right ventricular failure. In five of 10 patients, anatomic correction with either an arterial switch operation (three patients) or a pulmonary artery-to-aorta anastomosis and right ventricle-to-pulmonary artery conduit (two patients) was performed. Before anatomic correction in these five patients, four of five patients had a pulmonary artery band to prepare the left ventricle. The interval between preparation and correction ranged from 8 days to 12 months (median, 2 months). One patient died after an arterial switch operation. In the remaining five patients, coexisting left ventricular dysfunction precluded anatomic correction; all five patients survived cardiac transplantation. Survival for the entire group of 10 patients is 90%, and the median postoperative hospital stay was 17 days. During follow-up (12-62 months; median, 27 months), there were no deaths. Neoaortic insufficiency after anatomic correction was common (mild in one patient, moderate in two patients, and severe in one patient who required aortic valve replacement 4 months after surgery). In the transplantation group, one patient developed lymphoma 3 months after transplantation but is currently in remission after reduction of immunosuppression. CONCLUSIONS: In patients who develop late right ventricular failure after Mustard or Senning repair, surgical intervention with either anatomic correction or cardiac transplantation can be done with acceptable morbidity and low mortality. Neoaortic valve insufficiency demands close follow-up after anatomic correction.
Aorta, Thoracic↗