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Biomedical subjects

M L Brown

Publications and source records attributed to M L Brown.

At least 91 records · Page 5Linked to original sources
PubMed1993

Prostate cancer screening: what we know and what we need to know.

OBJECTIVE: To critically evaluate the evidence for recommending the screening of asymptomatic men for prostate cancer with a blood test to detect a prostate-specific antigen (PSA). DATA SOURCES: Relevant articles on screening for prostate cancer were identified from MEDLINE searches, from the authors' files, and from the bibliographies of identified articles. STUDY SELECTION: In the absence of controlled prospective trials, the studies are primarily retrospective and contain information about the sensitivity, specificity, and predictive values of tests used to screen for prostate cancer; the natural history of untreated prostate cancer; the morbidity, mortality, and costs of definitive treatment; and reviews of screening study biases. DATA EXTRACTION: Potential treatment-related mortality and costs that could be incurred by screening were estimated using defined assumptions. RESULTS: Although screening for prostate cancer has the potential to save lives, because of possible overdiagnosis, screening and subsequent therapy could actually have a net unfavorable effect on mortality or quality of life or both. Given the performance characteristics of the test, widespread screening efforts would probably cost billions of dollars. CONCLUSIONS: The net benefit from widespread screening is unclear. A randomized prospective study of the effect of screening on prostate cancer mortality has therefore been initiated by the National Cancer Institute.

Aged↗
PubMed1993

Regulation of expression of the ligand for CD40 on T helper lymphocytes.

Activated Th cells deliver contact-dependent signals to resting B lymphocytes that initiate and drive B cell proliferation. Recently, a ligand for the B lymphocyte membrane protein, CD40, has been identified that delivers contact-dependent Th cell signals to B cells. A dimeric soluble form of CD40 was produced and used to further characterize the regulation of expression of the CD40 ligand. Expression of the CD40 ligand was rapidly induced after Th lymphocyte activation, and its stability depended upon whether Th cells were activated with soluble or plastic-bound stimuli. Th cells activated with soluble stimuli rapidly turned over cell-surface CD40 ligand whereas Th cells activated with plastic-bound stimuli exhibited more stable CD40 ligand expression for up to 48 h. Removal of activated Th cells from the plastic-bound stimulus resulted in a rapid turnover of CD40 ligand, suggesting that continuous stimulation could maintain CD40 ligand expression. Ligation by soluble CD40 could also stabilize expression of CD40 ligand on the Th cell surface. Both CD40 ligand and IL-2 were transiently synthesized from 1 to 12 h after Th cell activation and had similar kinetics of synthesis. In Con A-activated Th cells newly synthesized CD40 ligand exhibited an initial high turnover (1.5 h t1/2) and after 5 h of Th cell activation became more stable (10-h t1/2). In Th cells activated with plastic-bound anti-CD3, CD40 ligand exhibited a similar biphasic turnover except that the rapid turnover phase began significantly later. This delay could allow more time for newly synthesized CD40 ligand to assemble or associate with other molecules and thus become stabilized on the cell surface. Newly synthesized CD40 ligand in Con A-activated Th cells appeared to not be efficient in delivering Th cell-dependent contact signals to resting B cells, implying the need for assembly or accessory proteins. Regulation of CD40 ligand expression was consistent with all the characteristics of Th cell-delivered contact signals to B cells and may contribute to the high degree of specificity in B cell responses.

Animals↗
PubMed1993

Cost-effectiveness of breast cancer screening: preliminary results of a systematic review of the literature.

There is now considerable concern that universal access to health care within realistic resource constraints requires some sort of cost-effectiveness analysis of given medical procedures and interventions. One such intervention is routine mammographic screening for breast cancer. Here, we report preliminary results from an ongoing project to conduct a systematic and comprehensive review and comparison of the published cost-effectiveness analyses of screening for the early detection of breast cancer. We examine 16 such studies, and compare two studies in detail to explain how differences in assumptions and in consideration of down-stream effects have caused the published results for apparently comparable breast cancer screening programs to span a broad range.

Breast Neoplasms↗
PubMed1993

Olestra, a nondigestible, nonabsorbable fat. Effects on gastrointestinal and colonic transit.

Olestra, the name proposed for the mixture of hexa-, hepta- and octaesters of sucrose and long-chain fatty acids, is a nondigestible, nonabsorbable lipid with physical properties and taste that are similar to those of natural triglycerides. Our aim was to determine whether substitution with up to 30 g of olestra in a 45-g fat meal would alter gastric, small bowel, and colonic transit. Five groups, each of six healthy volunteers, ingested 800-kcal, 22-g protein meals containing a total of 45 g of lipid (N = 24) or 15 g of lipid (N = 6). Among those receiving the 45-g fat meal, 0, 7.5, 15 and 30 g of lipid were substituted with olestra (N = 6 per group). The 15-g fat meal consisted entirely of natural triglyceride. A dual gamma camera scintigraphic method was used to estimate gastric and small bowel transit (99mTc pellets in the meal) and colonic transit (111In pellets). The latter was achieved by the delayed release of 111In pellets from a capsule coated with a pH-sensitive polymer, methacrylate, that disintegrated in the terminal ileum. There were no differences in the gastric, small bowel, or colonic transits of any of the five equicaloric meals. Some individuals had a significantly greater 48-hr stool weight after ingesting 15 g of olestra, but stool weights of subjects consuming 7.5 g or 30 g of olestra did not differ from controls. We conclude that substitution with olestra of up to 30 g in a 45-g fat meal does not significantly alter gastrointestinal transit in healthy subjects.

Adult↗
PubMed1993

Intra- and interobserver variability in interpretation of DMSA scans using a set of standardized criteria.

A set of criteria was developed to standardize assessment of DMSA renal scintigraphy which were performed to evaluate children for acute pyelonephritis and renal scarring. This study was undertaken to assess intra- and interobserver variability in the interpretation of DMSA renal scintigraphy using these criteria. Renal contours and parenchyma were assessed in three zones. Contours were assessed as normal or abnormal and parenchymal defects were evaluated in terms of character, shape and degree in three regions (upper and lower pole and midzone). Two nuclear medicine physicians blindly reviewed 57 DMSA scintigraphy on two occasions each. Disagreement of each observer's evaluation of the same scintigraphy on two different occasions was described as intraobserver variability, and the comparison between readings by each of the two observers was described as interobserver variability. High levels of intra- (95.9% and 90.6% respectively, p < 0.05) and interobserver agreement (84.4%, p < 0.05) were demonstrated. There were minor differences in inconsistencies between the two kidneys or different kidney zones. We conclude that standardization of criteria resulted in higher intra- and interobserver consistency in interpretation of DMSA scintigraphy.

Acute Disease↗
PubMed1993

Effect of menstrual cycle on esophageal emptying of liquid and solid boluses.

The effect of the menstrual cycle on esophageal emptying is unknown. We investigated the influence of the menstrual cycle on esophageal transit of liquid and solid boluses in 30 healthy, normally menstruating women who were 20 to 46 years of age. Each subject was studied during the follicular (days 8 through 10) and the luteal (days 18 through 20) phase of the menstrual cycle. Subjects swallowed a 10-ml bolus of water and two solid boluses, each radiolabeled with 100 microCi of 99mTc sulfur colloid. Esophageal scintigraphy was used to assess esophageal emptying of the liquid and solid boluses. Our results showed no significant differences in esophageal transit of either liquid or solid material between follicular and luteal phases. We conclude that esophageal emptying is unaffected by the phases of the menstrual cycle.

Adult↗
PubMed1993

Evaluation of 99Tcm nonspecific polyclonal IgG in the detection of rejection in a single lung transplant canine model.

Acute rejection is an important cause of graft failure in single lung transplantation, however, current noninvasive tests are neither sensitive nor specific for this diagnosis. The aim of this study was to determine whether 99Tcm-labelled human nonspecific polyclonal IgG (99Tcm-IgG) may serve as a marker for acute pulmonary rejection following allotransplantation in a dog model. Seventeen mongrel dogs were studied, including four controls and thirteen dogs which underwent surgery [right autotransplant recipient (n = 4), right unmodified allotransplant recipient (n = 5), and right immunosuppressed allotransplant recipient (n = 4)]. At 6 days following surgery, all dogs received 67Ga-citrate and 99Tcm-IgG. Two days later all dogs were sacrificed. Post-mortem examination revealed acute lung rejection in nine animals. No significant difference was found in the percentage uptake of both 99Tcm-IgG and 67Ga-citrate per gram of tissue between rejecting and nonrejecting transplanted lungs. In cases of moderate to severe rejection (n = 5), only 67Ga-citrate showed a significant difference (P = 0.03) in uptake between rejecting and contralateral native lungs, respectively. We conclude that 99Tcm-IgG does not accurately identify acute lung rejection in the early postoperative period.

Animals↗
PubMed1993

Cell Density and Growth Phase as Factors in the Resistance of a Biofilm of Pseudomonas aeruginosa (ATCC 27853) to Iodine.

Previous studies have shown that biofilms exhibit enhanced resistance to iodine. Investigations were conducted to determine the relative importance of growth phase versus cell density on biofilm resistance of Pseudomonas aeruginosa (ATCC 27853) to iodine. Cell density is a contributing factor to resistance, whereas growth to the stationary phase is not sufficient to achieve resistance.

Journal Article↗
PubMed1993

Evaluation of a radiolabeled somatostatin analog (I-123 octreotide) in the detection and localization of carcinoid and islet cell tumors.

The purpose of this study was to evaluate the usefulness of a radiolabeled analog of somatostatin (iodine-123 octreotide) in the detection and localization of known carcinoid and islet cell tumors and to correlate tumor uptake with the presence or absence of somatostatin receptors. I-123 octreotide studies were performed in 28 patients. Whole-body and tomographic studies were performed over a 2-day period after injection. Twenty-two of the 28 patients underwent tumor biopsy, and samples were analyzed for the presence of somatostatin receptors. Tumors were best seen on scans obtained 1-4 hours after injection. Of the 28 patients, 22 had positive scans with uptake in tumors, three showed photon-deficient uptake in regions of known tumor, and three had negative scans. Seventeen patients in whom results of tumor biopsy were positive for somatostatin receptors had positive scans, and one patient in whom results of biopsy were negative for somatostatin receptors had a negative scan. Previously unsuspected lesions were detected on the I-123 octreotide scans in four of the 28 patients. I-123 octreotide appears to be a useful tracer for the localization of neuroendocrine tumors and, most likely, other soft-tissue tumors as well.

Adenoma, Islet Cell↗
PubMed1993

Effect of elevated glucose on cyclic GMP and eicosanoids produced by porcine aortic endothelium.

The short-term effects of elevated glucose on cyclic GMP (cGMP) and eicosanoid production in pig aortic endothelial cell monolayers was determined by incubating cells in 5.5 mM or 44 mM glucose for 6 hours. Bradykinin- or A23187-stimulated cGMP production was significantly reduced in cells incubated in 44 mM glucose compared with 5.5 mM glucose. Stimulation of cGMP levels with exogenously added nitric oxide (NO) was also decreased to a similar extent in cells exposed to 44 mM glucose. These data suggest that NO production stimulated by bradykinin or A23187 was unchanged by elevated glucose. Assayed eicosanoids, including 6-ketoprostaglandin (PG) F1 alpha, PGE2 alpha, and 15(S)-hydroxy-(5Z, 8Z, 11Z, 13E)-eicosatetraenoic acid, stimulated by bradykinin or A23187, were increased in cells exposed to 44 mM glucose. These eicosanoid products formed from exogenously added arachidonic acid did not differ between cells incubated in 5.5 mM or 44 mM glucose. Hyperosmolar concentrations of mannose or sucrose had no effect on cGMP levels but did mimic the effect of elevated glucose on eicosanoid production. These data suggest that hyperglycemia in diabetes may interfere with NO-induced guanylate cyclase activation but not NO production in the endothelium and that increased phospholipase activity, secondary to hyperosmolarity, may account for elevated eicosanoid levels.

Animals↗
PubMed1993

Bone scintigraphy: Part 2. Orthopedic bone scanning.

Bone scanning provides a functional assessment of skeletal pathology not available with conventional radiography or special radiographic techniques such as CT and MRI. Bone scanning detects osteoblastic activity associated with many forms of orthopedic skeletal disease. Several of the more common orthopedic applications of bone scanning have been described above, while equally important topics such as prothesis loosening, avascular necrosis, and the reflex sympathetic dystrophy syndrome were not considered. Thus, for a great range of benign skeletal pathology, bone scanning can provide the orthopedic surgeon with practical information concerning the cause of the patient's pain, the true significance of otherwise questionable radiographic findings, the extent of disease and the results of orthopedic surgical treatment.

Arthrodesis↗
PubMed1993

Technical aspects of bone scintigraphy.

Optimal bone scintigraphy is obtained by using a current generation gamma camera with a high-resolution collimator, minimizing the patient-to-collimator distance, using scatter reduction techniques where possible, and obtaining a 500,000 to 1 million count image for 40-cm field of view camera. Hard copy images from an analog or digital formatter should be optimized to display all intensities either on the same images or, when necessary, to display the low count information on one image and the high count information on another. Additional images using different collimators, such as converging or pinhole collimators, and oblique and lateral views should be obtained when necessary to demonstrate or define the pathologic area. To optimize SPECT imaging, the following parameters should be used: a high-resolution collimator, a 128 x 128 acquisition matrix, and minimum separation between the patient and the collimator, which may require the use of an elliptic orbit. Between 64 and 128 views should be obtained, and depending on preference, the planar data should be prefiltered with a Butterworth, order 8-12 and a cutoff at 0.5 Nyquist. The data should then be reconstructed using a simple ramp filter. This method provides a good technique when one is first beginning to perform bone SPECT. Attenuation correction is not generally beneficial for SPECT bone studies, although sometimes weighted backprojection may improve image contrast and resolution. Finally, the use of volume rendering may help clarify the location of suspect lesions.

Bone and Bones↗
PubMed1993

Bone scintigraphy in benign and malignant tumors.

Bone scintigraphy is frequently performed in most radiology departments and is an excellent technique for evaluating both oncologic and benign disease processes. Careful attention to the technical aspects of bone scintigraphy as described in this article results in images of excellent quality.

Bone Diseases↗
PubMed1992

Elevated glucose alters A23187-induced release of arachidonic acid from porcine aortic endothelial cells by enhancing reacylation.

Cultured porcine aortic endothelial cells were conditioned in normal (5.2 mM) and elevated (15.6 mM) glucose, prelabeled with [14C]arachidonic acid and stimulated with ionophore A23187. Elevated glucose cultures released less radiolabeled products and less [14C]arachidonic acid. Analysis of cellular lipids revealed that elevated glucose reduced net loss of radiolabel from diacylphosphatidylethanolamine, did not affect early phosphatidylinositol hydrolysis, and increased net loss from diacylphosphatidylcholine and alkenylacylphosphatidylethanolamine. Uptake of radiolabel upon stimulation was examined to measure the role of reacylation on the diminished net release of radiolabel in elevated glucose cultures. Enhanced acylation of [3H]arachidonic acid into cellular lipids, especially PI, was observed in stimulated and resting cultures with elevated glucose. Further, pretreatment of the cultures with an acyltransferase inhibitor, thimerosal, prior to A23187 stimulation in radiolabeled cultures, abolished the effects of glucose on eicosanoid and arachidonic acid release. Differences in the ionophore-induced net loss of radiolabel from diacylphosphatidylethanolamine and phosphatidylinositol of the two glucose treatments were diminished by thimerosal exposure, while net loss of radiolabel from diacylphosphatidylcholine and alkenylacylphosphatidylethanolamine were unaffected. The data indicate that elevated glucose alters deacylation and enhances reacylation of arachidonic acid into endothelial cells and particularly into phosphatidylinositol. Enhanced reacylation may explain some of the altered lipid pathways that have been observed in experiments that elevate glucose concentrations or involve diabetes.

Acylation↗
PubMed1992

Specialized role for a murine class I-b MHC molecule in prokaryotic host defenses.

Although nonclassical (class I-b) gene products represent the majority of murine major histocompatibility complex (MHC) genes, the role of these relatively nonpolymorphic molecules remains uncertain. Recently, one such protein, H-2M3 (formerly designated Hmt), was shown to bind and specifically present N-formylated peptides to cytotoxic T lymphocytes. Because N-formylation is characteristic of prokaryotic proteins, this MHC molecule may be especially adapted for a role in the mammalian defense against bacterial attack. The current studies demonstrate that an MHC molecule, indistinguishable from H-2M3, presents antigens derived from the intracellular pathogen Listeria monocytogenes to Listeria-specific CD8+ cells.

Animals↗