Doctors who smoke. Doctors should advise but do not have to lead by example.
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Biomedical subjects
Publications and source records attributed to P O'Brien.
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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.
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.
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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.
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)
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)
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.
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.
New developments in pediatric heart transplantation have influenced the nursing management of these patients. The patient population has changed over the past few years with an increase in patients with congenital heart disease and larger numbers of infants and young children. The management of patients prior to transplantation has become more complex, with new pharmacologic agents and the use of mechanical assist devices as a bridge to heart transplantation. The importance of accurate assessment and management of pulmonary hypertension both before and after transplantation have been recognized. FK506, a new immunosuppressant in clinical trial, appears promising as both a maintenance therapy and a rescue drug with fewer side effects than cyclosporine. The trend toward outpatient and home care for many transplant-related therapies reflects the wider trend in health care. The practice of the critical care nurse involved in pediatric heart transplantation has been influenced by these recent changes.
The formation of hydroxyl radicals from a chromium(V) complex isolated from the reaction of glutathione with chromate has been demonstrated in spin trapping experiments using dimethylsulfoxide and 3,5-dibromo-4-nitrosobenzene sulfonate. Mechanisms for the formation of radicals in such systems are discussed. These results help to explain the ability of solutions containing chromate and glutathione to cause strand breaks in DNA.
Although the original Centers for Disease Control study of the relation between A/New Jersey/8/76 (swine flu) vaccine and Guillain-Barré syndrome (polyradiculoneuritis) demonstrated a statistical association and suggested a causal relation between the two events, controversy has persisted. To reassess this association, the authors obtained medical records of all previously reported adult patients with Guillain-Barré syndrome in Michigan and Minnesota from October 1, 1976 through January 31, 1977. To identify previously unreported hospitalized cases with onset of symptoms during this period, the authors surveyed medical care facilities. A group of expert neurologists formulated diagnostic criteria for Guillain-Barré syndrome and then reviewed the clinical records in a blinded fashion. Of the 98 adult patients from the original Centers for Disease Control study eligible for consideration, three were found to have been misclassified by date of onset and were excluded. Of the remaining 95, the 28 (29%) who did not meet the diagnostic criteria were equally distributed between the vaccinated group (18 of 60, 30%) and the unvaccinated group (10 of 35, 29%). In addition to the 67 remaining cases who met the diagnostic criteria, six previously unreported cases (three of whom had been vaccinated) were found and included in this analysis. The relative risk of developing Guillain-Barré syndrome in the vaccinated population of these two states during the 6 weeks following vaccination was 7.10, comparable to the relative risk of 7.60 found in the original study. These findings suggest that there was an increased risk of developing Guillain-Barré syndrome during the 6 weeks following vaccination in adults. The excess cases of Guillain-Barré syndrome during the first 6 weeks attributed to the vaccine was 8.6 per million vaccinees in Michigan and 9.7 per million vaccinees in Minnesota. No increase in relative risk for Guillain-Barré syndrome was noted beyond 6 weeks after vaccination.
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A retrospective analysis of 56 patients presenting with Hodgkin's disease involving the liver between 1970 and 1984 revealed a 10-year survival probability of 44%. The actuarial 10-year continuous progression free survival was 42%. Presentation variables predicting for relapse in the liver included hepatomegaly (P less than 0.025) or focal lesions on isotope, ultrasound or CT scan (P less than 0.01). These factors may define a context for investigation of adjuvant hepatic irradiation following chemotherapy.
Cerebral arteriovenous malformations (AVM), regardless of the mode of discovery, have an annual risk of hemorrhage of approximately 4 percent. A progressive obliterative vasculitis culminating in the occlusion of an AVM may be induced by the administration of radiation doses of approximately 20 Gy given in a single fraction. The process takes about two years and occlusion occurs in approximately 80% of patients so treated. Such a dose may be accurately administered to AVMs up to 3 cm in diameter with very little radiation imparted to the adjacent brain by means of multiple highly collimated radially arranged cobalt sources (the Gamma Knife) or by means of a modified linear accelerator turned through an arc or arcs with the target AVM as the centre of rotation. The Gamma Knife and the modified linear accelerator have nearly equal accuracy. Recent experience with modified linear accelerators indicates efficacy equal to the Gamma Knife. Both devices are effective treatment for small AVMs but the cost of modifying a pre-existing linear accelerator is only a few percent of the acquisition and installation costs of the Gamma Knife.
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Between 1971 and 1988, 20 patients with previously undiagnosed non-Hodgkin's lymphoma (NHL), of intermediate or high grade histology presented with extradural spinal cord compression. All had decompressive surgery. The first treatment after surgery was chemotherapy in nine and radiotherapy in 11 patients. At presentation 15% were ambulant and this improved to 55% after surgery; urinary continence improved from 30 to 80%. Mobility and sphincter control remained unchanged, regardless of subsequent therapy. Chemotherapy as the initial treatment modality after surgery, either alone or in combination with radiotherapy, did not jeopardise functional outcome. Mobility after surgery was an independent prognostic factor for survival, when corrected for age and stage at presentation (P = 0.04). The treatment of intermediate and high grade NHL presenting with spinal cord compression should be based on histology, extent of disease and age, as with other sites of presentation, but should also take into consideration the prognostic importance of post-surgical mobility.
The binding of a number of chromium complexes to ATP has been studied by 31P NMR spectroscopy. The results are consistent with the formation of outer-sphere complexes between ATP and the chromium species. The magnitude of the binding constant has been determined as approximately 500 mol-1 dm3 (pH = 7.00) for the interaction of trisethylenediamine chromium(III) with ATP. Under our experimental conditions no NMR signals are observed from complexes in which chromium(III) is bound directly to the phosphate groups of ATP. The relative stability of the inner sphere complexes of chromium(III) and glutathione or ATP is probably not a significant factor in determining the toxicity of chromium(III) complexes.