Biomedical subjects
Donald Smith
Publications and source records attributed to Donald Smith.
Lipid lowering by simvastatin induces regression of human atherosclerotic lesions: two years' follow-up by high-resolution noninvasive magnetic resonance imaging.
BACKGROUND: Statins are widely used to treat hypercholesterolemia and atherosclerotic disease. Noninvasive MRI allows serial monitoring of atherosclerotic plaque size changes. Our aim was to investigate the effects of lipid lowering with simvastatin on atherosclerotic lesions. METHODS AND RESULTS: A total of 44 aortic and 32 carotid artery plaques were detected in 21 asymptomatic hypercholesterolemic patients at baseline. The effects of statin on these atherosclerotic lesions were evaluated as changes versus baseline in lumen area (LA), vessel wall thickness (VWT), and vessel wall area (VWA) by MRI. Maximal reduction of plasma total and LDL cholesterol by simvastatin (23% and 38% respectively; P<0.01 versus baseline) was achieved after approximately 6 weeks of therapy and maintained thereafter throughout the study. Significant (P<0.01) reductions in maximal VWT and VWA at 12 months (10% and 11% for aortic and 8% and 11% for carotid plaques, respectively), without changes in LA, have been reported. Further decreases in VWT and VWA ranging from 12% to 20% were observed at 18 and 24 months. A slight but significant increase (ranging from 4% to 6%) in LA was seen in both carotid and aortic lesions at these later time points. CONCLUSION: The present study demonstrates that maintained lipid-lowering therapy with simvastatin is associated with significant regression of established atherosclerotic lesions in humans. Our observations indicate that lipid-lowering therapy is associated with sustained vascular remodeling and emphasize the need for longer-term treatment.
The multifocal ERG: unmasked by selective cross-correlation.
The purpose of this paper is to provide the reader with a better insight into the mechanisms of multifocal ERG (mfERG) recording. The construction of the first and second order mfERG responses were examined by recovering the response to specific pulse trains embedded in the m-sequence.A custom built pc based multifocal system driving a LED stimulator was used to record a 61 element mfERG and a global ERG. The global ERG recording was used to enable the recovery of different pulse trains embedded in the m-sequence. Summation of these individual pulse trains was performed and the results compared with the standard full cross-correlation. An isolated pulse response is defined as a flash of light that has no other flashes within two m-sequence base periods before or after the flash. This isolated pulse response was recovered from the raw data and this response input into a simple superposition model to predict the waveform shape for specific pulse trains. The superposition model was compared with the actual selective cross-correlation for a particular pulse train. The summations of the selective cross-correlation components give identical responses to the full cross-correlation. The superposition model also predicts the waveform shapes recovered by the selective cross-correlation procedure. The mfERG response is a complex composite response from a number of different pulse trains. Examination of the individual waveform shapes provides some insight into the origin of the mfERG waveform. The main contributions to the P1 component are the same as for an isolated response and as with the standard ERG this component is likely to be dominated by the mid retina. The N1 component is also likely to have similar origins to that of the isolated response but the amplitude is dominated by contributions from pulse trains where there is no change of state and therefore includes a component from the interaction between two consecutive stimuli. The N2 component is a composite response dominated by the interaction between two successive stimuli two base periods apart and the P1 component of a second stimulus delayed one frame from the first stimulus.
Vitamin C prevents hyperbaric oxygen-induced growth retardation and lipid peroxidation and attenuates the oxidation-induced up-regulation of glutathione in guinea pigs.
Hyperbaric oxygen therapy is used to treat various clinical conditions, but it also causes oxidative damage. The objectives of this study are to determine if increased vitamin C intake can prevent hyperbaric oxygen-induced damage and to determine interactions among vitamin C, glutathione and vitamin E in response to oxidative stress. The growth rates of unexposed guinea pigs fed 1.25 mg vitamin C/day were indistinguishable from that of guinea pigs fed 50 mg vitamin C/day. In contrast, hyperbaric oxygen exposure resulted in growth retardation in guinea pigs fed 1.25 mg vitamin C/day, but it had little effect on the growth rates of guinea pigs fed 50 mg vitamin C/day. Increased vitamin C intake also prevented hyperbaric oxygen-induced lipid peroxidation in the liver. In guinea pigs not exposed to hyperbaric oxygen, levels of vitamin C in tissues were closely related to vitamin C intake, but tissue levels of glutathione and vitamin E were not related to vitamin C intake. However, interactions between vitamin C and glutathione were observed upon chronic hyperbaric oxygen exposure. Chronic hyperbaric oxygen exposure resulted in >2-fold increases in the levels of glutathione in liver and lung of guinea pigs fed 1.25 mg vitamin C/day. In comparison, the oxidation-induced increases in glutathione were significantly attenuated in guinea pigs fed 50 mg vitamin C/day. These data show that increased intake of vitamin C can prevent or alleviate the hyperbaric oxygen-induced damage. The interactions between vitamin C and glutathione upon hyperbaric oxygen exposure indicate that there is a homeostatic regulation of antioxidant capacity in guinea pig tissues.
The relationship between lead in plasma and whole blood in women.
Studies have suggested that plasma lead levels may better reflect the toxicologically labile fraction of circulatory Pb that is more freely available for exchange with target tissues than do Pb levels in whole blood. Studies have also reported an apparent severalfold variation in the relative partitioning of Pb between whole blood and plasma (or serum) for a given whole-blood Pb level. This may reflect inherent differences in the plasma Pb/whole blood Pb partitioning among individuals and/or methodologic challenges associated with the collection and analyses of samples that generally contain < 1-2 ng total Pb. Here, we conducted a longitudinal assessment of the relationship between Pb in whole blood and plasma in environmentally exposed reproductive-age women (n = 63) living in Mexico City, Mexico. We collected whole blood and plasma samples using trace metal clean techniques and analyzed them for Pb using high-resolution inductively coupled plasma mass spectrometry. A subset of subjects provided repeated blood samples weekly for 4 consecutive weeks (n = 17 subjects) or every 1-2 months over a 9-month period (n = 14 subjects). Plasma Pb concentration was significantly positively associated with whole-blood Pb in a curvilinear fashion over the range of blood Pb values observed here (2.13-39.7 microg/dL). This relationship was best described by the function Plasma Pb = e (-2.392 + 0.0898 x blood Pb), where SE(coefficient) = 0.0054, SE(constant) = 0.063 (n = 63 subjects, n = 141 observations). Results from the short- and long-term repeated collection subjects indicated that the within- and between-subject variance components were not significantly different between the two subsets of subjects. The between-subjects component accounts for 78% of the variance in plasma Pb levels, while the residual variance (22%) may be attributed to other unmeasured factors. Collectively, this study demonstrates that plasma Pb measurements may be applied to general clinical settings, provided that established trace metal clean techniques are adopted. This study also shows that the relative (%) partitioning of whole-blood Pb in plasma naturally varies by a factor of about 2-4-fold among subjects at a given blood Pb level. Because Pb in the plasma is considered to more closely represent the fraction of Pb in the circulation that is readily exchanged with peripheral target tissues (e.g., brain, kidney, skeleton), the routine assessment of plasma Pb may provide a more meaningful measure of toxicologically available Pb.
Human experimentation: a game without rules.
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New York University Medical Center's pilot "Epo-Depot" program: a win-win for patients and health care.
Therapy associated with treatment-related anemia continues to be of great concern for health care providers. Patient satisfaction, patient adherence, and growing insurance reimbursement concerns related to Epoetin alpha therapy for anemia initiated the development of a nursing-led process improvement team at New York University (NYU) Medical Center. Multiple patient groups were identified and treated for anemia with Epoetin alpha through the guide of a standardized pathway providing a convenient and effective treatment plan. The treatment delivery had to be consistent with institutional reimbursement requirements while avoiding significant cost to the patient. Patient populations diagnosed with HIV anemia, HIV oncology, presurgical anemia, and medically complex anemia can now receive appropriate ambulatory treatment. This article describes the formation of the "Epo-Depot" and the logistics involved to service these patients with anemia.
Differential cyclooxygenase-2 enzyme expression in radiosensitive versus radioresistant glioblastoma multiforme cell lines.
BACKGROUND: Glioblastoma multiforme (GBM) is a high-grade primary brain tumor that is refractory to current forms of treatment. In cell studies, the growth rate of GBM cells correlates with the level of Cyclooxygenase-2 (COX-2) enzyme expression. COX-2 has been implicated in carcinogenesis of systemic cancers. Recently, COX-2 inhibition has been shown to increase the radiosensitivity of various tumors. We wished to assess whether the expression of COX-2 is greater in radioresistant versus radiosensitive forms of GBM. MATERIALS AND METHODS: The radiosensitive (A172) and radioresistant (T98G) Glioblastoma multiforme cell lines were assayed for COX-2 expression using standard immunofluorescence histochemistry. Fluorescence readings were recorded per field. Western blot analysis was performed on both A172 and T98G GBM cell lines. The radioresistant cells were exposed to incremental doses of radiation in the presence and absence of a COX-2-selective inhibitor. Radioresistant cells were then exposed to incremental doses of COX-2-selective inhibitor at a constant dose of radiation. RESULTS: The radioresistant cell line T98G had an approximate 1. 7-fold greater expression of COX-2 than did the radiosensitive cell line A172, as per immunofluorescence histochemistry. Western blot analysis confirmed this finding. Statistical analysis (Bonferroni/Dunn) showed the results to be significant (p<0.0001). The wells containing radioresistant cells exposed to incremental doses of radiation and COX-2 inhibitors appeared to have higher cell kill when compared to radiation alone. Furthermore, increasing the COX-2 inhibitor concentration yielded higher cell kill. CONCLUSION: The results presented here show that the radioresistant GBM cell line, T98G, has a greater expression of COX-2 than does the radiosensitive GBM cell line, A172. These results suggest that: (i) COX-2 expression may serve as a marker for assessing radioresistance in GBM, (ii) COX-2 inhibition may lower the required doses of postoperative radiation, (iii) COX-2 inhibitors may have a role in radiosensitizing otherwise radioresistant forms of GBM.
Review: increased physical activity and combined dietary changes reduce mortality in coronary artery disease.
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