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Biomedical subjects

J G Fletcher

Publications and source records attributed to J G Fletcher.

At least 19 recordsLinked to original sources

Contrast-enhanced CT colonography in recurrent colorectal carcinoma: feasibility of simultaneous evaluation for metastatic disease, local recurrence, and metachronous neoplasia in colorectal carcinoma.

OBJECTIVE: Contrast-enhanced CT colonography has the potential to detect local recurrence, metachronous disease, and distant metastases in patients with a history of invasive colorectal cancer. The purpose of our study was to determine whether colonic anastomoses prohibit adequate colonic distention on contrast-enhanced CT colonography and to estimate the performance of contrast-enhanced CT colonography in detecting recurrent colorectal carcinoma. MATERIALS AND METHODS: Fifty patients with a history of resected invasive colorectal carcinoma underwent contrast-enhanced CT colonography and colonoscopy. Colonic distention was graded for different colonic segments. Two radiologists evaluated for the presence of local recurrence, metachronous disease, and metastatic disease. Results were compared with colonoscopy, histology, and clinical follow-up. RESULTS: Most patients had adequate colonic inflation (37/50, 74%). Eleven of 13 patients with inadequate distention had collapse in the sigmoid colon, usually associated with ileocolic anastomoses. Contrast-enhanced CT colonography detected local recurrences with an accuracy of 94% (95% confidence interval, 83-99%). The accuracy of contrast-enhanced CT colonography for metachronous lesions greater than or equal to 1 cm was 92% (95% confidence interval, 80-98%), but there was only one such lesion, which was missed on initial colonoscopy. Stool, granulation tissue, and inflammation can mimic the CT appearance of local recurrence or metachronous disease and account for false-positive examinations. Contrast-enhanced CT colonography identified five patients with metastatic disease. CONCLUSION: Suboptimal sigmoid distention can be seen on contrast-enhanced CT colonography, predominantly in patients with right hemicolectomies. Contrast-enhanced CT colonography is a promising method for detecting local recurrence, metachronous disease, and distant metastases in patients with prior invasive colorectal carcinoma. The technique can also serve as a useful adjunct to colonoscopy by detecting local recurrences or metachronous disease that are endoscopically obscure or by serving as a full structural colonic examination when endoscopy is incomplete.

Adult↗

A comparison of endoscopic ultrasound, magnetic resonance imaging, and exam under anesthesia for evaluation of Crohn's perianal fistulas.

BACKGROUND & AIMS: To determine accuracy of endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) for evaluation of Crohn's disease perianal fistulas. METHODS: Thirty-four patients with suspected Crohn's disease perianal fistulas were prospectively enrolled in a blinded study comparing EUS, MRI, and examination under anesthesia (EUA). Fistulas were classified according to Parks' criteria, and a consensus gold standard was determined for each patient. Acceptable accuracy was defined as agreement with the consensus gold standard for > or =85% of patients. RESULTS: Three patients did not undergo MRI; 1 did not undergo EUS or EUA; and consensus could not be reached for 1. Thirty-two patients had 39 fistulas (20 trans-sphincteric, 5 extra-sphincteric, 6 recto-vaginal, 8 others) and 13 abscesses. The accuracy of all 3 modalities was > or =85%: EUS 29 of 32 (91%, confidence interval [CI] 75%-98%), MRI 26 of 30 (87%, CI 69%-96%), and EUA 29 of 32 (91%, CI 75%-98%). Accuracy was 100% when any 2 tests were combined. CONCLUSIONS: EUS, MRI, and EUA are accurate tests for determining fistula anatomy in patients with perianal Crohn's disease. The optimal approach may be combining any 2 of the 3 methods.

Adolescent↗

CT colonography without cathartic preparation: feasibility study.

PURPOSE: To evaluate methods for contrast material labeling of stool in the unprepared colon for computed tomographic (CT) colonography and to determine their sensitivity for polyp detection. MATERIALS AND METHODS: Fifty-six patients with suspected or known polyps were assigned to five groups. Two to seven doses of 225 mL of dilute contrast material were orally administered during 24 or 48 hours. Transverse CT images were assessed for effectiveness of stool labeling. Colonoscopy was performed in all patients and was the standard. Two radiologists blinded to prior imaging and colonoscopic results assessed polyp detection. RESULTS: For each group, average stool labeling scores and ranges were as follows: 24 hour two dose, 16% and 8%-21%; 24 hour five dose, 53% and 27%-66%; 48 hour four dose, 38% and 22%-48%; 48 hour six dose, 68% and 54%-77%; and 48 hour seven dose, 88% and 75%-98%. Sensitivity for the two radiologists for the identification of patients with polyps 1 cm or larger for each group was as follows: 24 hour two dose, 50% and 67%; 24 hour five dose, 100% and 100%; 48 hour four dose, 58% and 75%; 48 hour six dose, 56% and 67%; and 48 hour seven dose, 100% and 80%. CONCLUSION: Ingestion of contrast material adequately labels stool for lesion identification; a 48-hour lead time and multiple doses of contrast material are required. Sensitivity for polyp detection in patients with adequate stool labeling approaches the sensitivity for polyp detection in prepared colons.

Barium Sulfate↗

Carcinoid tumors of the stomach: a clinical and radiographic study.

OBJECTIVE: Our purpose is to describe associated and coexistent diseases of gastric carcinoid tumors, the unique biologic behavior of these tumors, the appearance of these tumors on fluoroscopic and CT images, and the radiologic management of these neoplasms. CONCLUSION: First, multiple gastric carcinoid tumors are associated with enterochromaffin-like cell hyperplasia, chronic atrophic gastritis, and pernicious anemia and have a low risk of malignancy. Second, solitary gastric carcinoid tumors, or gastric carcinoid tumors associated with multiple endocrine neoplasia-type I (MEN-I) and Zollinger-Ellison syndrome, have a higher potential for metastatic disease. Third, the radiologic appearance and management of these tumors depend on the clinical background of the patient.

Aged↗

Interactive fast spin-echo imaging.

It is shown that a spin-echo sequence may be used to acquire T(2)-weighted, high-resolution, high-SNR sections at quasi-real-time frame rates for interactive, diagnostic imaging. A single-shot fast spin-echo sequence was designed which employs driven equilibrium to realign transverse magnetization remaining at the final spin echo. Driven equilibrium is shown to improve T(2) contrast at a given TR, or conversely to reduce TR by approximately 1000 msec and thus increase temporal resolution while maintaining a given level of contrast. Wiener demodulation of k-space data prior to reconstruction is shown to reduce blurring caused by T(2)-decay while constraining noise often associated with other inverse filters. Images are continuously acquired, reconstructed, and displayed at rates of one image every one to two seconds, while section position and contrast may be altered interactively. The clinical utility of this method is demonstrated with applications to dynamic pelvic floor imaging and interactive obstetric imaging.

Computer Systems↗

CT colonography and MR colonography: current status, research directions and comparison.

With the introduction of multidetector technology in CT and the moveable table with integrated coil modules in MRI, the concept of multiorgan screening has become realistic. CT colonography and MR colonography are new radiologic techniques that promise to be highly sensitive colorectal screening examinations. This article reviews the current status and research directions in CT colonography and MR colonography, and compares these methods.

Colonic Neoplasms↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗