Biomedical subjects
Publications and source records attributed to J Sparkes.
We present a case of progressive atlanto-occipital dislocation, recognized by a new onset of positive neurologic findings. We discuss the anatomic relationship of the lower four cranial nerves to the foramen magnum and the atlanto-occipital joint. The importance of careful assessment of the cranial nerves prior to choosing a treatment algorithm is emphasized.
Increased proteolytic activity may be a factor in intimal hyperplasia after balloon angioplasty (BA). The objectives of this study were to assess elastase activity after BA in a rabbit arterial double-injury model and the effects of elastase inhibition. Elastase activity increased immediately after BA, reached an 8-fold peak at 1 week, and declined to baseline levels by 4 weeks. Elastin zymography showed that the elastase activity was associated predominantly with a molecular mass of 25 kDa. Elastase activity was significantly inhibited in vitro by elafin and phenylmethylsulfonyl fluoride, selective inhibitors of serine elastases. A second group of animals was transfected after BA with a plasmid containing the cDNA for either elafin or a control (chloramphenicol acetyltransferase, CAT) construct by using a hemagglutinating virus of Japan-liposome transfection technique. Arterial segments were obtained at 48 hours, 1 week, and 4 weeks to assess transgene expression, arterial wall elastase activity, and intimal cross-sectional area, respectively. Elafin transgene expression was evident at 48 hours and resulted in a significant (80%) inhibition of elastase activity compared with chloramphenicol acetyltransferase-transfected arteries. There was a 43% reduction in intimal cross-sectional area in elafin-transfected arteries (0.28+/-0.22 versus 0.16+/-0.07 mm(2) for CAT-transfected versus elafin-transfected arteries, respectively; P<0.05). These data suggest that an early increase in serine elastase activity after BA contributes to intimal hyperplasia. Serine elastase inhibition may be a potential therapeutic approach to inhibit intimal hyperplasia.
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BACKGROUND: The "organized approach" to cervical screening in Australia includes standardized quality assurance measures for laboratories. This study examines changes in the frequency and the positive predictive value of reporting severe abnormalities in cervical smears over a 3-year period as a guide to the effects of implementing these measures. METHODS: The results of screening in 6-month periods from January 1995 to December 1997 were determined. Biopsy follow-up for results in the high grade epithelial abnormality ("HGEA") and "inconclusive: possible HGEA" categories was obtained from the Western Australian Cervical Cytology Registry (CCR). RESULTS: Approximately 40,000 smears were examined in each 6-month period. The frequencies of reporting HGEA were 0.47%, 0.59%, 0.79%, 0.85%, and 0.84%, and 0.91% for the study periods (P < 0.001). For the inconclusive category, they were 0.24%, 0.18%, 0.24%, 0.31%, 0.38%, and 0.35% (P < 0.001). Biopsy follow-up was available for 83. 9%, 80.5%, 89.9%, 92.4%, 93.1%, and 90.3% of the HGEA results and for 78.6%, 71.7%, 80.5%, 75.0%, 87.1%, and 85.9% of the inconclusive results over the study periods. The yield of high grade lesions for the biopsied cases was 82.6%, 82.3%, 83.1%, 79.5%, 80.9%, and 79% for HGEA cases and 58.2%, 41.9%, 60.6%, 52.8%, 47.5%, and 54.1% for inconclusive cases. CONCLUSIONS: There was a doubling in the reporting of HGEA results, whereas the positive predictive value for biopsied cases remained at about 80%. Reporting rates for inconclusive: possible HGEA cases also doubled, but the yield of biopsy-proven, high grade lesions remained at about 50%. These changes occurred in the absence of ancillary testing and with targeted rescreening methods. A high rate of reporting HGEA, in combination with a high positive predictive value, is among the most important indicators of cervical cytology laboratory performance. Large improvements in results may occur using conventional methods of quality assurance. Cancer (Cancer Cytopathol)
BACKGROUND: Restenosis complicates 30% to 40% of angioplasty procedures and may be unrelated to traditional coronary risk factors. Homocysteine, lipoprotein(a), and methylenetetrahydrofolate reductase (MTHFR 677T) (a genetic determinant of plasma homocysteine concentrations) are novel risk factors for coronary artery disease. Their roles in restenosis are unclear, and the potential synergism between homocysteine and lipoprotein(a) has not previously been studied. The objective of this study was to determine the relations among homocysteine, lipoprotein (a), MTHFR 677T, and restenosis after percutaneous transluminal coronary angioplasty. METHODS: This prospective study enrolled patients with successful elective percutaneous transluminal coronary angioplasty or stenting of a single, de novo, native coronary lesion. Fasting blood was drawn the morning of the procedure for homocysteine, lipoprotein(a), and MTHFR 677T. Follow-up angiography was performed 6 months after the procedure or earlier if clinically indicated. All cineangiograms were analyzed quantitatively. RESULTS: A total of 144 (92%) of 156 eligible patients underwent follow-up coronary angiography. The overall angiographic restenosis rate (residual stenosis >50%) was 31%. Mean homocysteine concentration was 10.1 +/- 3.7 micromol/L. Plasma homocysteine concentrations were not significantly different in patients with or without angiographic restenosis (9.6 +/- 3.3 vs 10.3 +/- 3.8 micromol/L; P =.31). Mean lipoprotein(a) concentration was 21.2 +/- 20.1 mg/dL. Plasma lipoprotein(a) concentrations were not significantly different in patients with or without restenosis (21.9 +/- 21.8 vs 20.9 +/- 19.5 mg/dL). Homozygosity for MTHFR 677T was present in 6.5% and was not associated with increased restenosis. No interaction between homocysteine and lipoprotein(a) was detected. CONCLUSIONS: Homocysteine, lipoprotein(a), and MTHFR 677T are not associated with restenosis after percutaneous transluminal coronary angioplasty.
BACKGROUND: The fibrinolytic system is intimately involved in several processes that contribute to restenosis, including clot dissolution, cell migration, and tissue remodeling. However, the role of the individual activators (urokinase [uPA] and tissue plasminogen [tPA] activators) and inhibitors (plasminogen activator inhibitor [PAI-1]) of the fibrinolytic system in maintaining patency after coronary artery angioplasty and stenting is unclear. METHODS AND RESULTS: We prospectively studied 159 patients with stable angina who underwent successful elective angioplasty (n=110) or stenting (n=49) of de novo native coronary artery lesions. Plasma samples were drawn at baseline (before angioplasty) and serially after angioplasty (immediately afterward and 6 hours, 24 hours, 3 days, 7 days, 1 month, 3 months, and 6 months afterward). Antigen and activity assays were performed for uPA, tPA, and PAI-1. Follow-up quantitative coronary angiography was performed in 92% of eligible patients. The overall angiographic restenosis rate (diameter stenosis >50%) was 31% (37% in PTCA patients, 17% in stented patients). At all time periods, including baseline, uPA antigen levels were significantly higher and PAI-1 antigen levels were significantly lower in patients with restenosis. Restenosis rates for patients in the upper tertile of baseline uPA antigen levels were 2-fold higher than for those in the lower 2 tertiles (46% versus 24% and 22%, respectively; P<0.004). In a stepwise regression multivariate analysis, obstruction diameter after the procedure and uPA antigen were significant predictors of follow-up diameter stenosis. CONCLUSIONS: Plasma uPA antigen levels and PAI-1 antigen levels identify patients at increased risk for restenosis after percutaneous coronary revascularization.
The manufacture of Therapeutic BCG can and should be a controlled process, to ensure adequate treatment doses are received by CIS patients. Standardization of production methods and CFU potency testing methods are essential to ensure continued successful treatment of CIS. Stability data can be used to validate assumptions about Therapeutic BCG potency used in clinical trials. Accelerated heat degradation studies of Therapeutic BCG should not be used for predictions of shelf life, but can be used for comparative purposes.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.