Biomedical subjects
P J Sweeney
Publications and source records attributed to P J Sweeney.
Transient cortical blindness after coronary angiography.
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Effect of subcutaneous recombinant human erythropoietin in cancer patients receiving radiotherapy: final report of a randomized, open-labelled, phase II trial.
The purpose of this study was to determine the safety, efficacy and impact on quality of life of recombinant human erythropoietin (r-HuEPO) for cancer patients undergoing radiotherapy (RT). An open-labelled randomized design was used, with patients randomized to either treatment or control arms. Patients in the treatment arm received r-HuEPO given by subcutaneous injection at a dose of 200 units kg(-1) day(-1) plus oral iron supplements (ferrous sulphate 325 mg p.o. t.i.d.). Entry was restricted to patients with carcinoma of the lung, uterine cervix, prostate or breast who presented for RT with anaemia parameters reflective of 'the anaemia of chronic disease'. Radiotherapy policies (portals, doses, fraction size, etc.) were determined by the site and stage of disease. Complete blood counts (CBCs) were obtained weekly. The target level of haemoglobin was 15 g dl(-1) for men and 14 g dl(-1) for women. Quality of life (QOL) was assessed weekly by using an analogue scale to judge energy, activities of daily living and overall quality of life. Forty-eight patients were entered in the study, 24 in the treatment arm and 24 in the control arm. The prerandomization demographic characteristics and mean laboratory values were comparable in both arms. The mean haemoglobin at completion was 13.6 g dl(-1) for r-HuEPO-treated patients compared with 11.0 g dl(-1) for control subjects (P = 0.0012). Patients who received r-HuEPO demonstrated a mean weekly haemoglobin increase of 0.41 g dl(-1) compared with a decrease in mean haemoglobin level in controls for 6 of the 7 weeks of the study (mean weekly decrease of 0.073 g dl(-1)). Target levels of haemoglobin were achieved by 41.6% of r-HuEPO-treated patients compared with none of the control subjects. The mean platelet count declined in both arms of the study with RT but the decline from pretreatment was less rapid in r-HuEPO-treated patients (11.2% decrease) compared with controls (26.3% decrease) and was statistically significant during weeks 4-6. Toxicity was minor with only mild irritation at the injection site. Mean quality of life end points were superior in the treatment arm but not statistically significant. r-HuEPO had a beneficial effect on weekly haemoglobin levels in patients undergoing RT with response rates similar to other studies. There was also a less rapid decline in weekly platelet counts in r-HuEPO-treated patients compared with control subjects. Further studies are needed to address the optimum dose and scheduling as well as the impact of r-HuEPO on clinical outcomes.
A bolt from the blue: lightning strike to the head.
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Functional imaging in treatment planning of brain lesions.
PURPOSE: Explore the use of functional imaging data in radiation treatment planning of brain lesions. METHODS AND MATERIALS: Compare the treatment-planning process with and without the use of functional brain imaging for clinical cases where functional studies using either single photon emission computed tomography or magnetic resonance imaging are available. RESULTS: A method to register functional image data with planning image studies is needed for functional treatment planning. Functional volumes are not simply connected regions. One activation study may produce many isolated functional areas. After finding the functional volumes and registering the functional information with the planning imaging data, the tools used for conventional three-dimensional treatment planning are sufficient for functional treatment planning. However, the planning system must provide dose-volume histograms for volumes of interest that consist of isolated pieces. Treatment plans that spare functional brain while providing identical target coverage can be constructed for lesions situated near the functional volume. However, the dose to other areas of the brain may be increased. CONCLUSIONS: Functional imaging will make determination of dose response of eloquent areas of the brain possible when combined with volumetric dose information and neuropsychological evaluation prior to and after radiation therapy. Realizing the full potential of functional imaging studies will require improved delineation of activated volumes and determination of the uncertainties in functional volume delineation. Optimization of treatment plans by minimizing dose to volumes activated during functional imaging studies should be used cautiously, because the dose to "silent," but possibly eloquent, brain may be increased.
How Dr. Lewy (Lewey) spelled his name.
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What's in a name? Dr. Lewey and the Lewy body.
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Introduction to the NMR of proteins.
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Synthesis and analysis of the enantiomers of calmidazolium, and a 1H NMR demonstration of a chiral interaction with calmodulin.
Calmidazolium [R24571, 1-[bis(4-chlorophenyl)methyl]-3-[2-(2,4-dichlorophenyl)-2-[(2,4- dichlorophenyl)methoxy]ethyl]-1H-imidazolium chloride] is a potent calmodulin inhibitor. This paper describes the synthesis and properties of the enantiomers of calmidazolium from the enantiomers of miconazole [1(N)-(2-(2,4-dichlorobenzyloxy)-2-(2,4 dichlorophenyl))-ethyl imidazole], prepared from the racemate by chiral preparative scale high performance liquid chromatography. Overlap between ligand and protein resonances in the aromatic region of the 1H NMR spectrum of the calmidazolium-calmodulin complexes has been obviated by preparation of the protein with all of its nine phenylalanine rings deuterated (Phe-d5 calmodulin). This has been accomplished by the overexpression of calmodulin derived from Trypanosoma brucei rhodiesiense in E. coli in a medium supplemented with ring-deuterated phenylalanine. The kinetics of binding of each enantiomer are slow on the 1H NMR time scale as judged by the behaviour of the H2 resonance of Histidine-107, which is clearly visible under the sample conditions used. The aromatic spectral regions of the protein-bound (+) and (-) enantiomers contrast strikingly, reflecting differences in bound environment and/or conformation.
Anaplastic carcinoma of the thyroid.
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Repositioning accuracy of a noninvasive head fixation system for stereotactic radiotherapy.
We report on the repositioning accuracy of patient setup achieved with a noninvasive head fixation device for stereotactic radiotherapy. A custom head mask which attaches to our stereotactic radiosurgery head ring assembly is fabricated for each patient. The position and orientation of a patient in the stereotatic space at the time of treatment are determined from analyzing portal films containing images of radio-opaque spheres embedded in a custom mouthpiece. From analysis of 104 setups of 12 patients, we find that the average distance between the treated isocenter and its mean position is 1.8 mm, and that the standard deviations of the position of the treated isocenter in stereotactic coordinate space about its mean position are less than 1.4 mm in translation in any direction and less than 1 degree of rotation about any axis.
Clinical evaluation of cervical radiculopathy and myelopathy.
This article considers the entities of cervical radiculopathy and myelopathy. Beginning with a brief historical note and neuroanatomy review of the cord and nerve roots, the discussion proceeds with analysis of symptoms and signs of cervical root disease and then compressive cervical myelopathy. A discussion of diagnostic testing and a differential diagnosis follows. A brief review of conservative medical therapy concludes the article.
Continuing medical education: a lifelong commitment.
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Parkinson's disease: managing symptoms and preserving function.
Two strategies of drug therapy for Parkinson's disease (PD) are neuroprotective and symptomatic. In early PD, selegiline may delay need for symptomatic treatment, but whether this represents a delay in disease progression remains controversial. The decision to begin symptomatic therapy depends on how disabling or troublesome symptoms are to the patient. Anticholinergics are often used as monotherapy for alleviation of early tremor. When levodopa is added, it may be reasonable to begin with the controlled-release form. The variety of dopamine agonists used as adjunctive agents is increasing. Research continues on surgical therapies and fetal tissue transplantation.
High resolution 2-dimensional electrophoretic analysis of proteins in saline bladder washings.
Human urine contains a spectrum of proteins derived from various organs in the body. This investigation was undertaken to identify a group of proteins secreted primarily by bladder urothelium. Saline bladder washouts were collected from 9 male and 4 female patients undergoing routine cystoscopic examination. Each sample was sieved, desalted, freeze-dried and solubilized in urea mix. identical amounts of proteins were pooled according to donor sex. All individual and pooled samples were then subjected to 2-dimensional gel analysis using the ISO-DALT system. Profiles of both groups of subjects were highly reproducible, comparable and resembled those of urine and plasma. Several hundred spots were visualized although most of them as yet remain unrecognized. The proteins identified in bladder washouts include albumin, transferrin, IgG gamma-heavy chain, Gc-globulin, alpha 1-antichymotrypsin, alpha 1-antitrypsin, alpha 1-acid glycoprotein, G4, IgG light chains, alpha 1-microglobulin, and low and high density lipoproteins. Most importantly, while some abundant urinary macromolecules such as Tamm-Horsfall mucoprotein and most acidic urinary proteins were undetectable, albumin and transferrin were relatively less expressed. The 2-dimensional profiles we developed can be used as a data base to study urothelium derived proteins in various disease conditions such as bladder cancer.
Prevalence of positive urine drug screens in a prenatal clinic: correlation with patients' self-report of drug use.
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Radiation therapy in head and neck cancer: indications and limitations.
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Electrophoretic techniques for the analysis of synthetic amyloid beta-A4-related peptides.
Two electrophoretic techniques have been developed for the analysis of synthetic beta-A4 related peptides. The first is an acetic acid--urea--polyacrylamide gel electrophoresis denaturing system while the second employs capillary zone electrophoresis at pH 7. Both methods were calibrated to identify the state (monomeric or aggregate) of the longer amyloid fragments beta-A4(1-40) and beta-A4(1-43) during analysis.