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J Sunderland

Publications and source records attributed to J Sunderland.

27 records · Page 2Linked to original sources

Decision logic for retreatment of asymptomatic lung cancer recurrence based on positron emission tomography findings.

PURPOSE: The purpose of the study was to determine if Positron emission tomography (PET) 2-[F-18] fluoro-2-deoxy-D-glucose (FDG) imaging could detect subclinical local lung cancer recurrence and whether retreatment of such recurrence was feasible and beneficial. METHODS AND MATERIALS: Twenty patients with biopsy proven lung cancer were studied with Positron emission tomography for the purpose of detecting subclinical lung cancer recurrence over a period of 4.25 years. All patients were treated with external radiation as part or all of their therapy. Twenty patients had baseline PET and computed tomography (CT) studies for comparison with later studies. Surviving patients had a total of 40 sequential PET scans and 35 CT scans. The follow-up interval ranged from 5 to 40 months posttreatment. The differential uptake ratio (DUR) was determined for regions of interest of increased FDG uptake. RESULTS: The median DUR value of the 20 baseline PET studies was 5.59. The DUR value of greater than 3 was empirically selected as being positive for tumor detection. On baseline studies, PET had a 100% correlation with the CT findings in regard to detection of the site of primary tumor involvement. Four of 20 patients showed areas of discordance in the mediastinal and hilar areas on initial PET and CT studies. Seven of 17 patients showed discordant posttreatment PET-CT findings. Two false positive PET studies were due to radiation pneumonitis and one to macrophage glycolysis in tumor necrosis. For detection of asymptomatic tumor recurrence, analysis of sequential PET and CT studies, biopsy results, and the patient's clinical course suggested that PET had a sensitivity of 100%, specificity of 89.3%, and accuracy of 92.5%. Computerized Tomography was found to have a sensitivity of 67%, specificity of 85%, and accuracy of 82% for detection of such early-stage recurrence. Five patients went on to have retreatment with external irradiation based upon the PET evidence. Four retreated patients had biopsies that corroborated the positive PET findings, and one patient was retreated on the basis of the qualitative appearance of the posttreatment PET study. Two of the five retreated patients remain alive without evidence of tumor to 34 months following initial therapy. CONCLUSION: Positron emission tomography scanning appears to be effective in detecting and following the progression of recurrent lung cancer. Retreatment of patients with asymptomatic recurrent tumor has resulted in absent or decreased FDG activity. Monitoring of patients with PET may provide prolonged survival in patients who otherwise would fail treatment because of local tumor recurrence.

Adenocarcinoma↗

Is polyploidy an important genotoxic lesion?

The importance of polyploidy as a genotoxic lesion is uncertain and there have been few publications and no reviews which have included data on spontaneous or induced polyploidy in routine genotoxicity screening. We have attempted to clarify some of the issues by reviewing the published literature and by reference to our historical data base for metaphase analysis of cultured human lymphocytes. In our studies on pharmaceutical compounds polyploidy was the lesion most often found, being induced by approximately 40% of the compounds tested. The mean spontaneous frequency was between 0.1 and 0.3%, and values for polyploidy induction were 5-fold to > 100-fold the spontaneous value. Spontaneous polyploids tended to be near-exact multiples of the haploid chromosome number whereas induced 'polyploids' were, in fact, very heteroploid with a wide range of chromosome numbers. Polyploidy induction often occurred at non-toxic concentrations, usually there were well defined no-effect (threshold) levels and it was unrelated to other genetic effects. Such observations would be expected for inducers of polyploidy because the target molecules are not DNA and for these non-DNA targets there is usually a degree of redundancy. Therefore, inducers of polyploidy are only likely to be a hazard for humans if they are positive at or below therapeutic concentrations. We conclude that polyploidy/near-polyploidy (shown as 'polyploidy' throughout) should be scored as accessory data which becomes important only when induction occurs at therapeutic levels.

Chromosome Aberrations↗

Adenosine in myocardial perfusion imaging using positron emission tomography.

Because of its unique ability to demonstrate the metabolic consequences of myocardial ischemia, positron emission tomography (PET) is extremely valuable in assessing myocardial viability. PET imaging can identify the myocardial segments that are likely to improve after revascularization and may be more sensitive and specific for the detection of coronary artery disease compared with thallium perfusion imaging. Adenosine has several advantages over dipyridamole as a pharmacologic stress agent for use with PET. It produces maximal vasodilation in a significantly greater percentage of patients, is a more potent coronary vasodilator, and its very short half-life may be ideal for use with the very short half-life radioactive tracers used in PET. When combined with metabolic studies, adenosine may be useful for the assessment of patients who received thrombolytic therapy for an acute myocardial infarction.

Adenosine↗

Noscapine-induced polyploidy in vitro.

The conditions under which noscapine causes high levels of polyploidy in vitro in human lymphocytes were investigated to try to determine its mode of action and to assess whether it was likely to be a genotoxic hazard when used as an antitussive agent. Irrespective of duration of treatment or type of medium, there seemed to be a threshold for polyploidy induction between 15.0 and 30.0 micrograms/ml and a maximum between 100.0 and 150.0 micrograms/ml noscapine. High levels (10.0-20.0%) of noscapine-induced polyploidy were never found with 4 h treatments or with RPMI 1640 medium plus 15% (v/v) foetal calf serum; the use of Iscove's modified Dulbecco's medium and 24 h treatments were needed. The reasons for these observations seemed to be the faster cell division and greater sensitivity of cells grown in Iscove's medium. There was conflicting evidence about the mechanism of polyploidy induction by noscapine; either spindle damage or cell fusion remain as possibilities. The need for prolonged exposure and the precise nutritional requirements suggest that a short exposure, albeit at high concentration, in the upper gastro-intestinal tract is unlikely to be a hazard for humans. Furthermore, evidence of a threshold at approximately 20 micrograms/ml plus the virtual elimination of noscapine-induced polyploidy by microsomal metabolism (S9 mix) together with published metabolic data imply that the low-level systemic exposure after absorption may well not be hazardous. We conclude that the use of noscapine in cough mixtures does not pose a significant potential hazard for humans.

Bromodeoxyuridine↗

Enumeration of phagocytosed Staphylococcus aureus inside cells of the mouse macrophage cell line J774 by bioluminescence, fluorescence and viable counting techniques.

In order to quantify intracellular Staphylococcus aureus within a macrophage-like cell line by a bioluminescence technique, the mouse cell line J774 and opsonized Staphylococcus aureus were incubated together to allow phagocytosis to occur. Experiments using UV microscopy and fluorescent stained S. aureus were performed to determine an estimate of the mean intracellular bacterial numbers. For enumeration of intracellular bacteria by a bioluminescence technique, extracellular bacteria were removed by washing, the macrophages lysed mechanically and osmotically and treated with apyrase to remove somatic ATP. Bacterial cells were washed and the intracellular ATP measured by firefly luciferase bioluminescence in a luminometer. This new method of enumerating intracellular bacteria was compared to the conventional method of viable counts and found to correlate (r = 0.78). The bioluminescence assay developed was found to be a relatively rapid alternative method to the techniques currently used to enumerate intracellular bacteria and could prove advantageous in studies of intracellular killing and effects of antimicrobial agents on intracellular pathogens.

Animals↗

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Holidays↗