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Biomedical subjects

J G Fletcher

Publications and source records attributed to J G Fletcher.

At least 37 records · Page 2Linked to original sources
PubMed2000

Optimization of CT colonography technique: prospective trial in 180 patients.

PURPOSE: To assess the added benefits of prone positioning in addition to supine positioning and oral iodinated contrast medium for help in the detection of colonic polyps at computed tomographic (CT) colonography. MATERIALS AND METHODS: CT colonography was performed in prone and supine positions in 180 patients with polyps or risk factors for colonic neoplasia. Patients were randomly assigned to receive a standard bowel preparation or a standard preparation plus oral iodinated contrast medium. One radiologist interpreted supine images alone, and another analyzed supine and prone images. All patients subsequently underwent colonoscopy. RESULTS: At colonoscopy, 121 large (> or =1-cm-diameter) polyps and 142 smaller (0.5-0.9-cm) polyps were identified. Prone positioning resulted in increased sensitivity for identification of patients with large (> or =1-cm) polyps (increase from 70% to 85%, P: =.004) and of patients with polyps 0.5 cm or larger (increase from 75% to 88%, P: <.005), with no change in specificity. Use of oral contrast medium did not significantly improve polyp detection even in the subset of patients in whom colonic fluid attenuation was markedly increased. CONCLUSION: Acquisition and review of supine and prone CT colonographic images significantly improves the ability to identify patients with polyps 0.5 cm in diameter or larger. Administration of oral iodinated contrast medium does not significantly improve polyp detection.

Colon↗
PubMed1994

Cell death induced by peroxidized low-density lipoprotein: endopepsis.

Peroxidized low-density lipoprotein (p-LDL) has been previously demonstrated to be preferentially cytotoxic to certain malignant cells compared to normal cells of the same type. We present evidence that p-LDL is at least partially taken up through the LDL receptor and that it becomes localized in lysosomes. The integrity of lysosomes of p-LDL-treated cells is compromised, and leakage of their contents into the cytosol occurs. This leakage occurs early and precedes mitochondrial dysfunction. Brefeldin A inhibits this leakage, perhaps by interfering with the traffic between endosomes and lysosomes. Electron micrographs taken at various times suggest a mechanism of cell death which resembles certain aspects of the broad definition of apoptosis. However, we suggest that the cell death observed following p-LDL-induced release of lysosomal contents is essentially unique, with released lysosomal enzymes degrading the cell from within. We suggest that this process should be described as endopepsis.

Adenocarcinoma↗
PubMed1991

Selective cytotoxicity of low-density lipoprotein to helper T cells of cutaneous T-cell lymphoma after photoperoxidation with 8-methoxypsoralen.

Lymphocyte-containing plasma subjected to photolysis in the presence of 8-methoxypsoralen (methoxsalen, 8-MOP) has previously been shown to be effective against cutaneous T-cell lymphoma and the AIDS-related complex. The mechanism of this effect was thought to involve photoreaction of 8-MOP with DNA, based on certain in vitro experiments. The results of this study suggest a different mechanism. Low-density lipoprotein (LDL) from fresh human plasma was photosensitized by addition of 8-MOP and exposure to UV light (mp-LDL), and the reactions of the LDL lipids and the chemical actions induced by these reactions were monitored. In a separate procedure, LDL was peroxidized with hydrogen peroxide and peroxidase (p-LDL). mp-LDL and p-LDL were then tested in cytotoxicity assays on HuT-78 helper T cells of cutaneous T-cell lymphoma. These results indicate that (a) LDL in plasma in the presence of very low concentrations of 8-MOP (200 ng/mL) can be peroxidized by UV light; (b) this photoperoxidized LDL is cytotoxic to helper T cells of cutaneous T-cell lymphoma in a dose-dependent manner; but (c) it does not kill normal lymphocytes under similar conditions. The findings also suggest alternative therapeutic strategies for treatment of cutaneous T-cell lymphoma, such as direct utilization of peroxidized LDL.

Cell Survival↗
PubMed1991

In situ neutron spectrometry to 60 MeV in a water phantom exposed to a cancer therapy beam.

In-air and in-phantom neutron spectra have been measured between 10 and 60 MeV for two field sizes on the Clatterbridge cyclotron by unfolding the response of a specially built NE213 scintillator. The in-phantom measurements show distinct spectral hardening with depth, which is reflected in changes in the spectrum-averaged mean neutron energy. These findings are confirmed using Monte Carlo calculations.

Fast Neutrons↗
PubMed1990

Oxygenation of fluorinated tyrosines by mushroom tyrosinase releases fluoride ion.

The reactions of 2-fluoro- and 3-fluoro-L-tyrosine with mushroom tyrosinase have been investigated. Both fluorinated tyrosines are good substrates for tyrosinase, with Vmax and Vmax/Km values similar to those for L-tyrosine. Oxygenation of 2-fluorotyrosine is regioselective, and only 6-fluorodopa was detected by HPLC in reaction mixtures. Oxygenation of both isomers of monofluorotyrosine results in fluoride ion production in the absence of ascorbic acid; however, 2-fluorotyrosine also produces fluoride in the presence of ascorbic acid. These results are consistent with previous studies demonstrating rapid intramolecular cyclization of nascent 6-fluorodopaquinone (M.E. Rice, B. Moghaddan, C.R. Creveling, and K.L. Kirk, 1987, Anal. Chem. 59, 1534-1538), which is competitive with reduction by ascorbate, resulting in elimination of the aromatic fluorine as fluoride ion.

Basidiomycota↗
PubMed1989

Exercise hemodynamics and gas exchange in patients with chronic obstruction pulmonary disease, sleep desaturation, and a daytime PaO2 above 60 mm Hg.

Nocturnal oxyhemoglobin desaturation (NOD) has been reported in patients with disease of the pulmonary parenchyma and/or chest wall. The resulting hypoxemia could play a role in the development of pulmonary hypertension. We have previously demonstrated a small but statistically significant difference in resting pulmonary artery pressure (Ppa) and pulmonary vascular resistance (PVR) between two groups of patients with COPD of similar age, symptomatology, and degree of pulmonary dysfunction. These two groups were selected only on the basis of the presence or absence of NOD, and all had a mean daytime PaO2 at or above 60 mm Hg. The present study uses exercise to stress the pulmonary circulation of two groups of patients similar to the above. The purpose was to see if exercise can amplify underlying cardiopulmonary hemodynamic differences between NOD and non-NOD subjects. In addition, we attempted to confirm or refute previous studies which claimed that exercise desaturation correlates with NOD. Resting supine, resting upright, and upright exercise cardiopulmonary hemodynamics were measured using an indwelling right heart catheter, and arterial blood and expiratory gases were collected to assess metabolic and other gas exchange parameters. Although both groups showed increase in Ppa during exercise, the increases in systolic Ppa, mean Ppa, and driving pressure were disparately higher in subjects with NOD. Exercise desaturation was not predictive of NOD. The presence of NOD was predictive of a resting PVR greater than 120 dyne.s.cm-5, whereas mean sleep SaO2 and daytime PaO2 were unable to discriminate patients with COPD above or below this level.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗
PubMed1989

Pulmonary vascular hemodynamics in chronic lung disease patients with and without oxyhemoglobin desaturation during sleep.

Nonapneic, nocturnal oxyhemoglobin desaturation (NOD) during rapid-eye-movement (REM) sleep has been proposed as a predecessor and possible etiologic factor in the development of pulmonary hypertension in patients both with restrictive and obstructive chronic lung disease. The association between abnormal waking cardiopulmonary hemodynamics and NOD has not been established in patients with mild daytime hypoxemia. Gas exchange, pulmonary function, red cell mass, radionuclide gated cardiac ejection fraction, and supine cardiopulmonary hemodynamics were examined in 36 patients with chronic lung disease. All had a daytime PaO2 greater than 60 mm Hg and REM sleep-related NOD for greater than 5 minutes, to 85 percent or lower. These data were compared to those from 13 subjects with similar symptoms and objective measures of pulmonary dysfunction but without evidence of NOD. Patients with NOD showed more end organ evidence of hypoxemia and more abnormal cardiopulmonary hemodynamics than patients with similar degrees of lung disease but without NOD. The relative role of daytime vs nocturnal hypoxemia in inducing hemodynamic differences between groups cannot be determined from this study.

Heart↗
PubMed1987

Urinary catecholamines before and after tracheostomy in patients with obstructive sleep apnea and hypertension.

Obstructive apnea (asphyxia) is accompanied by acute elevation of systemic blood pressure. The usual nocturnal fall in blood pressure seen during sleep in normals may be absent in patients with repetitive apneas, and daytime systemic hypertension is reported to occur in up to 90% of such patients. Increased sympathetic activity in response to repetitive nocturnal episodes of asphyxia could explain the reversal of the diurnal pressure variation but not the daytime systemic hypertension in this setting. We examined diurnal variation in urinary catecholamines in eight subjects with severe apnea before and after tracheostomy. Five obese hypertensive subjects without apnea served as controls. Three urine specimens, two awake (7 a.m. to 3 p.m. and 3 p.m. to 11 p.m.) and one asleep (11 p.m. to 7 a.m.) were collected preoperatively and again 10-14 days postoperatively when the patient was free of pain and signs of stoma infection. All specimens were analyzed for epinephrine, norepineprine, metanephrine, and normetanephrine by liquid chromatography with electrochemical detection. Urinary epinephrine and metanephrine were not different between subjects and controls. Norepinephrine and normetanephrine were significantly higher in apneic subjects pretracheostomy as compared either with controls or with their own values posttracheostomy. Diurnal variation was not seen before or after tracheostomy. Only two of the controls showed significant diurnal variation in norepinephrine. We conclude that the absence of diurnal variation in catecholamines prior to tracheostomy reflects increased nocturnal sympathetic activity. Elevation of daytime norepinephrine and normetanephrine with return to control levels following tracheostomy implies increased sympathetic activity throughout the day.

Adult↗
PubMed1987

Long-term cardiopulmonary sequelae in patients with sleep apnea and chronic lung disease.

Both obstructive sleep apnea and chronic lung disease can be associated with intermittent or chronic hypoxemia leading to pulmonary hypertension and cor pulmonale. When these problems coexist, it is possible that the cardiopulmonary effects are additive. We hypothesized that hemodynamic disturbances in patients with apnea and lung disease would be more severe than in those with apnea alone, and that hemodynamic improvement should follow apnea cure, but perhaps at a slower rate than in those with apnea alone. To test these hypotheses, we prospectively followed 24 patients with sleep apnea syndrome. They were divided into 3 nonrandomized groups. Nineteen patients had both apnea and lung disease. Nine of these agreed to curative tracheostomy (Group 1). The other 10 subjects (Group 2) refused tracheostomy but accepted noncurative therapies, including nocturnal oxygen (n = 9), uvulopalatopharyngoplasty (n = 2), and protriptyline (n = 4). Five subjects with apnea but without clinically obvious lung disease received tracheostomies (Group 3). Subjects were followed at yearly intervals (mean follow-up, 27.2 months) with radionuclide motion studies and, in 15 of 24 who consented, right heart catheterization. The 3 groups did not vary with respect to age, percent ideal weight, or severity of apnea symptoms. The severity of right-sided hemodynamic dysfunction in the group with apnea but no obvious lung disease was less than that in the 2 groups with lung disease. A substantial decrease in pulmonary artery pressure (p = 0.056) and significant improvement in right ventricular ejection fraction occurred in the tracheostomized group with both apnea and lung disease. Pulmonary vascular resistance decreased in both groups receiving tracheostomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease↗
PubMed1987

Nocturnal oxyhemoglobin desaturation in COPD patients with arterial oxygen tensions above 60 mm Hg.

We studied 152 COPD patients with a daytime PaO2 greater than or equal to 60 mm Hg using formal polysomnography (EEG, airflow, respiratory muscle movement, ear oximeter) to detect the presence of nocturnal, nonapneic, oxyhemoglobin desaturation. Nine subjects were disqualified by the unexpected discovery of sleep apnea, as were another eight because they could not sleep in the laboratory setting. Of the remaining 135 subjects, 37 (27 percent) desaturated below a baseline sleep saturation of 90 percent for five minutes or more, reaching a nadir saturation of at least 85 percent. Anthropomorphic, pulmonary function, and historic factors comparing desaturators and nondesaturators failed to separate the groups. Awake PaO2 at rest in the desaturators was significantly lower than in the nondesaturators. The PaCO2 was higher in the desaturators. Reversibility of the desaturation phenomenon was demonstrated in three patients during subsequent polysomnographic studies following periods of clinical improvement. Continuous oxyhemoglobin monitoring during sleep remains the only reliable tool for detecting nocturnal desaturation.

Aged↗
PubMed1986

Occupational cadmium exposure in jig solderers.

The cadmium body burden, blood and urine cadmium concentrations, and renal function were studied in a group of 53 cadmium solderers. The results showed raised blood and urine cadmium concentrations and raised cadmium body burden in all workers (31) with more than five years exposure, with 27 having urine cadmium concentrations in excess of the proposed biological threshold of 10 nmol/mmol creatinine. Renal tubular dysfunction was found in 17 of the subjects with more than five years exposure and in one this was associated with glomerular dysfunction. These data indicate that cadmium body burden and frequency of tubular dysfunction in end users of cadmium may be as high as those found in smelters or production workers. Subjects with tubular dysfunction did not show greatly increased urine cadmium concentrations compared with those without dysfunction, supporting a previous suggestion that tubular dysfunction occurs before the wash out of cadmium from the kidney. At the time of our study, cadmium exposure stopped as cadmium free soldering rods were introduced. Repeat urine samples from 19 subjects, one to two years after exposure ended indicated that there was no further increase in the level of excretion of low molecular weight proteins, perhaps indicating that the tubular proteinuria does not increase or more severe renal dysfunction develop without continuous exposure.

Adult↗
PubMed1983

Renal dysfunction in cadmium smelters: relation to in-vivo liver and kidney cadmium concentrations.

Biochemical indicators of renal dysfunction have been compared with liver and kidney cadmium levels measured by neutron activation analysis in a group of 37 cadmium smelters. Higher than normal concentrations of cadmium in the liver reflect past exposure; they were associated with evidence of renal dysfunction in workers exposed to cadmium for more than 10 years. A small group of 6 workers exposed to cadmium for only a short time (mean = 4.6 years) had high hepatic cadmium concentrations but normal renal function. Longitudinal studies are required to establish the natural history of renal dysfunction following cadmium accumulation in industrial workers.

Cadmium↗
PubMed1975

Large data base at the Lawrence Livermore Laboratory.

The Lawrence Livermore Laboratory Octopus network includes a central storage facility of over 10-12 bits. This facility is accessed through a directory mechanism which permits flexible organization and general sharing of files by many time-sharing users. The chief problems of the system are not unusual: the maintenance of high transfer rates, of reliability and availability, and of sufficient storage capacity.

California↗