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Biomedical subjects

R Lee

Publications and source records attributed to R Lee.

At least 91 records · Page 5Linked to original sources

Application of finite difference time domain method for the design of birdcage RF head coils using multi-port excitations.

A three-dimensional finite difference time domain model was developed where the high pass birdcage coil and the imaged object are analysed as a single unit. A study was performed comparing linear, conventional quadrature, and four-port excitation at 64 MHz and 200 MHz for different coil loadings, namely muscle phantoms and an anatomically detailed human head model. A phase array concept was utilized to excite the birdcage coil in four ports. Two phase conditions were analyzed, the simple fixed phase and the variable phase. At 200 MHz, compared to the conventional quadrature drive, the four-port drive reduces the effects of the tissue-coil interactions leading to more uniform currents on the coil legs and consequently to a better B(1) field homogeneity. Also at 200 MHz, driving the coil in four ports provides an SAR distribution with peak values that are significantly less than those with linear or quadrature excitations.

Head↗

Computational analysis of the high pass birdcage resonator: finite difference time domain simulations for high-field MRI.

In this work, a finite difference time domain (FDTD) algorithm is validated at 1.5 tesla using the standard GE Signa quadrature head coil and a muscle phantom. The electrical characteristics of the birdcage head coil are then calculated for the linear and quadrature cases. Unlike previous computational analysis which assume idealized currents on the end rings and the struts of the resonator, a complete computational analysis is provided. This treatment considers the coupling between the resonator and the sample and includes a real coil excitation, a complete current derivation, and a thorough description of both B(1) fields and RF radiation. With this improvement, electromagnetic phenomena such as radiation, standing wave currents on the wires, and field inhomogeneities due to interactions between the coil and the load inside the coil are observed. At 200 MHz, it is demonstrated that this particular coil does not work well due to radiation and non-uniformities on the struts of the device. Also, at this frequency magnetic field inhomogeneities become large when the coil is loaded with a phantom.

Computer Simulation↗

Restoration of low resolution metabolic images with a priori anatomic information: 23Na MRI in myocardial infarction.

A new iterative extrapolation image reconstruction algorithm is presented, which enhances low resolution metabolic magnetic resonance images (MRI) with information about the bounds of signal sources obtained from a priori anatomic proton ((1)H) MRI. The algorithm ameliorates partial volume and ringing artefacts, leaving unchanged local metabolic heterogeneity that is present in the original dataset but not evident at (1)H MRI. Therefore, it is ideally suited to metabolic studies of ischemia, infarction and other diseases where the extent of the abnormality at (1)H MRI is uncertain. The performance of the algorithm is assessed by simulations, MRI of phantoms, and by surface coil 23Na MRI studies of canine myocardial infarction on a clinical scanner where the injury was not evident at (1)H MRI. The algorithm includes corrections for transverse field inhomogeneity, and for the leakage of intense signals into regions of interest such as 23Na MRI signals from ventricular blood ringing into the myocardium. The simulations showed that the algorithm reduced ringing artefacts by 15%, was stable at low SNR ( approximately 7), but is sensitive to the positioning of the (1)H MRI boundaries. The 23Na MRI showed hyperenhancement of regions identified as infarcted at post-mortem histological staining. The areas of hyperenhancement were measured by five independent observers in four 23Na images of infarction reconstructed with and without the algorithm. The infarct areas were correlated with areas determined by post-mortem histological staining with coefficient 0.85 for the enhanced images, compared to 0.58 with the conventional images. The scatter in the amplitude and in the area measurements of ischemia-associated hyper-enhancement in 23Na MRI was reduced by the algorithm by 1.6-fold and by at least 3-fold, respectively, demonstrating its ability to substantially improve quantification of the extent and intensity of metabolic changes in injured tissue that is not evident by (1)H MRI.

Algorithms↗

Circulating T-cell response to Helicobacter pylori infection in chronic gastritis.

BACKGROUND: Helicobacter pylori elicits a specific humoral and cellular immune response. There is increasing evidence that the type of T-cell response contributes to clinical outcome in H. pylori infection. MATERIALS AND METHODS: The host response to H. pylori infection in 34 subjects with chronic gastritis was examined in terms of T-cell proliferation and cytokine production in whole-blood cultures stimulated or unstimulated with H. pylori acid-glycine extract antigens (AGE). RESULTS: The proliferative response in whole-blood cultures was similar for both H. pylori-positive and -negative subjects stimulated with H. pylori AGE. While an increase in interferon-gamma (IFN-gamma) production was observed from both H. pylori-positive and -negative subjects with gastritis, significantly higher levels of IFN-gamma were detected in the former when stimulated with H. pylori AGE. In contrast, interleukin 4 (IL-4) was undetectable regardless of antigen stimulation. However, if an in situ IL-4 antibody capture assay was used, antigen-independent production of IL-4 was detected, but there was no difference between H. pylori-positive and -negative subjects with gastritis. After eradication of H. pylori, antigen-induced production of IL-4 was increased, with no decrease in the levels of secretion of IFN-gamma. IL-4 production was dependent on CD4+ T cells, as addition of anti-CD4 but not anti-CD8 mouse monoclonal antibody or matched IgG isotype to the whole-blood culture inhibited the production of IL-4. CONCLUSION: The results suggest that a shift toward a balanced Th1-Th2 response due to an increase in antigen-induced IL-4 production from CD4+ T cells follows eradication. We suggest that the downregulation of mucosal inflammation consequent on reduction in antigen levels or removal of downregulation after eradication of H. pylori contributes to this shift in cytokine balance.

Adult↗

Validation of a high-performance liquid chromatography method for the assay of and determination of related organic impurities in nevirapine drug substance.

Nevirapine (Viramune), a dipyridiodiazepinone, is a potent and highly specific nonnucleoside inhibitor of HIV-1 reverse transcriptase. This paper describes the validation of a specific, sensitive, and stability-indicating high-performance liquid chromatography method for the assay and determination of related organic impurities in nevirapine drug substance. This method uses a Supelcosil LC-ABZ column, a mobile phase of 20:80 (v/v) acetonitrile-25mM NH4H2PO4 (pH 5.0), and ultraviolet detection at a wavelength of 220 nm. This method was validated for specificity, linearity, accuracy, repeatability, detection limit, quantitation limit, stability of analyte solutions, robustness, and intermediate precision. Nevirapine is completely separated from all impurities. The method is shown to be linear with coefficients of determination r2 greater than 0.999. Average accuracy is 100.4% with a relative standard deviation of 0.7% for the assay. Accuracy ranges from 100.1 to 102.6% for related organic impurities. Repeatability is good, with relative standard deviations not more than 1.4%. The detection limit and the quantitation limit are determined to be 0.001 and 0.003%, respectively. Relative response factors of known organic impurities are determined, permitting the use of nevirapine at the 0.1% level as an external standard for the quantitation of these impurities. Analyte solutions are shown to be stable for at least 2 days at ambient temperature. The method is validated as robust, and intermediate precision is high. A system suitability test is developed and validated, and requirements are set.

Chromatography, High Pressure Liquid↗

Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer in vivo.

PURPOSE: Cyclooxygenase (COX)-2, an inducible enzyme which catalyzes the formation of prostaglandins from arachidonic acid, is expressed in prostate cancer specimens and cell lines. To evaluate the in vivo efficacy of a COX-2 inhibitor in prostate cancer, NS398 was administered to mice inoculated with the PC-3 human prostate cancer cell line. MATERIALS AND METHODS: A total of 28 male nude mice were inoculated subcutaneously with 1 million PC-3 cells. Tumors were palpable in all 28 animals 1 week after inoculation and mice were randomized to receive either vehicle (control) or NS398, 3 mg./kg. body weight, intraperitoneally three times weekly for 9 weeks. Tumors were measured at weekly intervals. After a 10-week experimental period, mice were euthanized and tumors were immuno- histochemically assayed for proliferation (PCNA), apoptosis (TUNEL) and microvessel density (MVD) (Factor-VIII-related antigen). Tumor VEGF content was assayed by Western blotting. RESULTS: NS398 induced a sustained inhibition of PC-3 tumor cell growth and a regression of existing tumors. Average tumor surface area from control mice was 285 mm.2 as compared with 22 mm.2 from treated mice (93% inhibition, p <0.001). Immunohistochemical analysis revealed that NS398 had no effect on proliferation (PCNA), but induced apoptosis (TUNEL) and decreased MVD (angiogenesis). VEGF expression was also significantly down regulated in the NS398-treated tumors. CONCLUSIONS: These results demonstrate that a selective COX-2 inhibitor suppresses PC-3 cell tumor growth in vivo. Tumor growth suppression is achieved by a combination of direct induction of tumor cell apoptosis and down regulation of tumor VEGF with decreased angiogenesis

Animals↗

Theoretical model for an MRI radio frequency resonator.

A theoretical model is described for a magnetic resonance imaging (MRI) radio-frequency resonator (an MRI "coil") that is useful at ultrahigh frequencies. The device is a "TEM resonator," which is based on a concept originally proposed by Röschmann (1988). The coil comprises a circular cavity-like structure containing several coaxial transmission lines operating in a transverse electromagnetic (TEM) mode. The model developed herein treats the empty coil and is based on multiconductor transmission line theory. This work generalizes and extends similar analyses of the device by Röschmann (1995) and Chingas and Zhang (1996). The model employs explicit calculation of per-unit-length parameters for TEM lines having arbitrary geometries. Calculations of the resonator's frequency response are found to compare well with measurements. Fields produced by linear (single-point) and quadrature drive are also computed and compared to images of low-permittivity phantoms.

Electromagnetic Fields↗

Skeletal growth estimation using radiographic image processing and analysis.

An automated knowledge-based vision system for skeletal growth estimation in children is reported in this paper. Images were obtained from hand radiographs of 32 male and 25 female children of age 1-16 yr. Phalanx bones were automatically localized and segmented using hierarchical inferences and active shape models, respectively. A number of shape descriptors were obtained from the segmented bone contour to quantify skeletal growth. From these descriptors, a feature vector was selected for a regression model and a Bayesian estimator. The estimation accuracy was 84% for females and 82% for males. This level of accuracy is comparable to that of expert pediatric radiologists, which suggests that the proposed approach has a potential application in pediatric medicine.

Adolescent↗

Paternal versus maternal transmission of a stimulatory G-protein alpha subunit knockout produces opposite effects on energy metabolism.

Heterozygous disruption of Gnas, the gene encoding the stimulatory G-protein alpha subunit (G(s)alpha), leads to distinct phenotypes depending on whether the maternal (m-/+) or paternal (+/p-) allele is disrupted. G(s)alpha is imprinted, with the maternal allele preferentially expressed in adipose tissue. Hence, expression is decreased in m-/+ mice but normal in +/p- mice. M-/+ mice become obese, with increased lipid per cell in white and brown adipose tissue, whereas +/p- mice are thin, with decreased lipid in adipose tissue. These effects are not due to abnormalities in thyroid hormone status, food intake, or leptin secretion. +/p- mice are hypermetabolic at both ambient temperature (21 degrees C) and thermoneutrality (30 degrees C). In contrast, m-/+ mice are hypometabolic at ambient temperature and eumetabolic at thermoneutrality M-/+ and wild-type mice have similar dose-response curves for metabolic response to a beta(3)-adrenergic agonist, CL316243, indicating normal sensitivity of adipose tissue to sympathetic stimulation. Measurement of urinary catecholamines suggests that +/p- and m-/+ mice have increased and decreased activation of the sympathetic nervous system, respectively. This is to our knowledge the first animal model in which a single genetic defect leads to opposite effects on energy metabolism depending on parental inheritance. This probably results from deficiency of maternal- and paternal-specific Gnas gene products, respectively.

Adrenergic beta-Agonists↗

Fixed, dilated pupils in the ICU: another recoverable cause.

A 41-year-old woman presented unconscious with fixed dilated pupils following a massive overdose of carbamazepine and an unknown quantity of venlafaxine prescribed for the management of bipolar affective disorder. Her course in the intensive care unit was marked by a number of complications related to the overdose including prolonged coma, seizures and cardiac arrest. The patient eventually recovered to leave hospital.

Adult↗

The cAMP signaling pathway as a therapeutic target in lymphoid malignancies.

Certain subsets of lymphoid cells, such as thymocytes or peripheral B cells, undergo apoptosis after treatment with agents which elevate intracellular 3',5' cyclic adenosine monophosphate (cAMP). Investigators have also noted induction of apoptosis of chronic lymphocytic leukemia (CLL) cells following treatment with methylxanthines, a phenomenon that may, at least in part, be due to the activity of these drugs as non-specific phosphodiesterase (PDE) inhibitors. We discuss three general strategies for altering cAMP-mediated signal transduction in lymphoid cells. After a review of what is known about the expression and regulation of PDE families in human lymphoid cells, we focus on the use of isoform-specific PDE inhibitors as potential therapeutic agents in CLL. Our work has suggested that despite the presence of PDE1, PDE3B, PDE4 and PDE7 enzymes in CLL, inhibition of PDE4 results in uniquely potent induction of apoptosis in CLL cells. This effect is relatively specific as comparable treatment of human peripheral blood T cells does not induce apoptosis. Clinical trials utilizing PDE4 inhibitors are indicated in the therapy of CLL patients resistant to standard therapy.

3',5'-Cyclic-AMP Phosphodiesterases↗

Baseline blink rates and the effect of visual task difficulty and position of gaze.

PURPOSE: To compare the baseline blink rates (BBR) measured under different (baseline) conditions, and to compare the blink rates measured when performing two visual tasks of different levels of difficulty at two positions of gaze. METHODS: In the first single masked experiment, BBR were measured under three different conditions - (i) conversation with the subjects (ii) taking the visual acuity and (iii) keeping the subjects waiting in an empty examination room. In the second single masked experiment, the subjects were required to perform an easy task (reading normal English words) and a difficult task (reading mirror-image English words) at primary gaze and down gaze. The orders of the tasks performed were randomly allocated. RESULTS: BBR taken under the three different conditions were significantly different from each other. No significant difference was found between the blink rates measured when performing the two reading tasks if they were performed at the same position of gaze. The mean blink rates were significantly lower when performing the tasks at down gaze than when performing the tasks at primary gaze. No significant differences were found between BBR-waiting and blink rate measured when the subject was doing the easy task at primary gaze, and between BBR-VA and blink rate measured when the subject was performing the difficult task at primary gaze. CONCLUSIONS: BBR measured under different (baseline) conditions produced different results so it is important for investigators to describe the baseline condition very clearly in studies where BBR are measured. Our results also indicated that mean blink rate was affected by the position of gaze and not the level of task difficulty.

Adult↗

Perforation of jejunal diverticulum: case report and review of literature.

We report the case of a 90-year-old woman, previously diagnosed with jejunal and colonic diverticula, who presented with left lower quadrant abdominal pain suggesting either colonic diverticulitis or ischemic colitis. A computed tomography scan revealed a perforated jejunal diverticulum with abscess formation. The patient promptly was treated surgically without complications. A review of the literature indicates the rarity of perforation of jejunal diverticula and the difficulty of early diagnosis. We discuss the etiology, pathogenesis, diagnosis, and management of this rare entity. It is important for primary care physicians to be familiar with this disease. Delay in work-up often results in catastrophic consequences.

Abdominal Pain↗

Metabolic acidosis and composite nutritional index (CNI) in CAPD patients.

BACKGROUND: Metabolic acidosis (MA) has been recognized as an important stimulus for net protein catabolism. Continuous ambulatory peritoneal dialysis (CAPD) is regarded to have advantage in normalizing the acid-base homeostasis over hemodialysis due to continuous supply of buffer. However, many CAPD patients still remain acidotic and the clinical impact of this MA is uncertain. Recent studies revealed no specific correlation between a certain degree of MA and protein nutritional status while others showed that mild alkalosis is nutritionally beneficial to CAPD patients. A cross-sectional study evaluating acid-base and nutritional status was performed to examine the relationship between acid-base status and overall nutritional status assessed by composite nutritional index (CNI) and to get a basic information about the optimal pH/HCO3 in CAPD patients. PATIENTS AND METHODS: Total 198 clinically stable patients maintained on CAPD more than 6 months were evaluated. Each of 10 nutritional parameters of CNI consisting of clinical (subjective global assessment), biochemical (total lymphocyte count, albumin, prealbumin, insulin-like growth factor-1, transferrin) and anthropometric parameters (body mass index, % lean body mass, triceps skinfold thickness, midarm muscle circumference) was graded from 0 to 3 point (0; normal, 1; mildly decreased, 2; moderately decreased, 3; severely decreased). RESULTS: Mean CNI score was 8.2 +/- 5.2 with a range of 0 to 25. CNI was positively correlated with age, duration of peritoneal dialysis, incidence of peritonitis, C-reactive protein (CRP), HCO3 and dialytic protein loss whereas it was inversely correlated with hemoglobin and nPNA. In patients with MA (n = 25, mean arterial HCO3 19.5 +/- 1.9 mM/l), CNI score was significantly lower (6.3 +/- 3.5) compared to patients with normal acid-base status (n = 63, 9.5 +/- 5.9, p < 0.01) or metabolic alkalosis (n = 47, 10.1 +/- 4.6, p < 0.001). Multiple regression analysis revealed that the incidence of peritonitis, duration of dialysis, CRP and dialytic protein loss were the independent predictors of CNI. CONCLUSIONS: CAPD patients with mild to moderate degree of MA appear to be associated with more favorable overall nutritional status expressed as CNI. Prospective studies evaluating changes in the nutritional parameters with the correction of acid-base abnormality are needed to understand the real impact of acid-base status on nutritional status and to know the optimal pH/HCO3 in CAPD patients.

Acidosis↗

The experience of nausea during sustained hyper-gravity flight with negligible angular velocity.

BACKGROUND: The purpose of this study was to investigate nausea and vomiting during hyper-gravity flight at a slow rate of turn. During head-movements under these conditions, the semi-circular canals of the vestibular system function normally whereas the otoliths experience a G-excess effect, displacing further and moving faster than in a 1 G field. HYPOTHESIS: Nausea and vomiting are greater during hyper-gravity flight compared with historical data collected in a 1 G field at a similar rate of turn. METHODS: There were 27 subjects who were exposed to 1.8 G (hyper-G) during a slow rate turn on three NASA KC-135 flights. Subjects participated in one of three experimental periods, each period consisting of two 5.5-min hyper-G runs: 1) rest, with only incidental head movements; 2) active roll and pitch head movements; or 3) passive roll head movements. Subjective symptom data were collected pre-flight, following each experimental period and post-flight using a standardized nausea questionnaire. Electrogastrograms were obtained from eight subjects. RESULTS: Seven subjects (26%) vomited during the flight. Nausea initially increased but was then stable throughout the flight. Nausea appeared highest during active head movements. In subjects who vomited, greater gastrointestinal distress and somatic distress were reported. CONCLUSIONS: The levels of nausea and vomiting observed during hyper-G cannot be explained by Coriolis cross coupling and are likely due to the G-excess effect on the otoliths. The nausea profiles observed in individuals who vomit during hyper-G appear similar to those previously observed during nausea produced by an optokinetic drum stimulus in a 1-G field.

Adult↗

CADMIUM II: acquisition and representation of radiological knowledge for computerized decision support in mammography.

CADMIUM II is a system for the interpretation of mammograms. A novel aspect of the system is that it combines symbolic reasoning with image processing, in contrast with most other approaches, which use only image processing and rely on artificial neural networks (ANNs) to classify mammograms. A problem of ANNs is that the advice they give cannot be traced back to communicable diagnostic inferences. Our approach is to provide advice based on explicit knowledge about the diagnostic process. To this end, we have conducted a knowledge elicitation study which looked at the descriptors used by expert radiologists when making diagnostic decisions about mammograms. The analysis of the radiologists' reports yielded a set of salient diagnostic features. These were used to inform the advice provided by the symbolic decision making component of CADMIUM II.

Breast Diseases↗