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Biomedical subjects

G Pang

Publications and source records attributed to G Pang.

At least 19 recordsLinked to original sources

Efficacy and safety of rifabutin-containing 'rescue therapy' for resistant Helicobacter pylori infection.

BACKGROUND: Current 'rescue' therapies provide inadequate Helicobacter pylori eradication rates because of antibiotic resistance. AIM: To test the efficacy of a modified triple regimen combining rifabutin, pantoprazole and amoxicillin as rescue therapy for patients in whom eradication of H. pylori had failed standard clarithromycin-based triple therapy. METHODS: One hundred and thirty patients (mean age 51.7 +/- 14.8 years) who had failed one or more eradication attempts with omeprazole, clarithromycin and amoxicillin were treated for 12 days with rifabutin 150 mg daily, amoxicillin 1 g or 1.5 g t.d.s, and pantoprazole 80 mg t.d.s. RESULTS: The intention-to-treat and per-protocol eradication rates were 90.8/90.8%. Metronidazole or/and clarithromycin resistance had no significant impact on H. pylori eradication rates. A higher overall eradication rate of 96.6% (95% CI: 92.1-101%) was obtained in patients treated with a regimen containing 1.5 g amoxicillin t.d.s compared with 90.7% (95% CI: 82-98.6%) using a regimen with 1 g amoxicillin t.d.s but the difference was not significant. Side-effects reported in 40% of patients were mild. CONCLUSION: A 12-day course of low dose of rifabutin with an increased dose of amoxicillin and pantoprazole is well-tolerated and highly effective against dual-resistant H. pylori infection after failure of triple therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Chronic Chlamydia pneumoniae infection may promote coronary artery disease in humans through enhancing secretion of interleukin-4.

Atherosclerosis is an inflammatory response, probably to a range of initiating causes. Chronic infection with Chlamydia pneumoniae (C.pn) has been suggested as one cause, but the nature of the association is controversial, in large part due to lack of an identified mechanism to link infection with the atherosclerotic process in man. This study examined 139 consecutive subjects with stable chest pain, with the aim of correlating the serological status of C.pn infection with the pattern of secretion of cytokines from CD4(+) T lymphocytes. C.pn seropositive subjects secreted significantly more interleukin (IL)-4 than did those who were C.pn seronegative (P = 0.02). No significant difference was noted for secreted interferon (IFN)-gamma. The amount of secreted IL-4, but not of secreted IFN-gamma, correlated positively with the extent of coronary artery disease (P = 0.006). A similar correlation with secreted IL-4 was not identified with Helicobacter pylori infection. These results support the hypothesis that C.pn infection contributes to the inflammatory process responsible for coronary artery atherosclerosis. The method used to detect cytokine secretion involves ligation of CD40L on blood CD4(+) T cells, which may have relevance to tissue events.

Aged↗

Electronic portal imaging based on cerenkov radiation: a new approach and its feasibility.

Most electronic portal imaging devices (EPIDs) developed so far use a Cu plate/phosphor screen to absorb x rays and convert their energies into light, and the light image is then read out. The main problem with this approach is that the Cu plate/phosphor screen must be thin (approximately 2 mm thick) in order to obtain a high spatial resolution, resulting in a low x-ray absorption or low quantum efficiency for megavoltage x rays (typically 2-4%). In addition, the phosphor screen contains high atomic number (high-Z) materials, resulting in an over-response of the detector to low-energy x rays in dosimetric verification. In this paper, we propose a new approach that uses Cerenkov radiation to convert x-ray energy absorbed by the detector into light for portal imaging applications. With our approach, a thick (approximately 10-30 cm) energy conversion layer made of a low-Z dielectric medium, such as a large-area, thick fiber-optic taper consisting of a matrix of optical fibers aligned with the incident x rays, is used to replace the thin Cu plate/phosphor screen. The feasibility of this approach has been investigated using a single optical fiber embedded in a solid material. The spatial resolution expressed by the modulation transfer function (MTF) and the sensitivity of the detector at low doses (approximately one Linac pulse) have been measured. It is predicted that, using this approach, a detective quantum efficiency of an order of magnitude higher at zero frequency can be obtained while maintaining a reasonable MTF, as compared to current EPIDs.

Equipment Design↗

Reversal in fatigued athletes of a defect in interferon gamma secretion after administration of Lactobacillus acidophilus.

BACKGROUND: Fatigue and impaired performance in athletes is well recognised and has been loosely linked to "overtraining". Reduced concentration of IgA in the saliva and increased shedding of Epstein Barr virus (EBV) have been associated with intense training in elite athletes. OBJECTIVE: To determine whether athletes presenting with fatigue and impaired performance had an immune defect relevant to defective containment of EBV infection, and whether a probiotic preparation (Lactobacillus acidophilus) shown to enhance mucosal immunity in animal models could reverse any detected abnormality. RESULTS: The fatigued athletes had clinical characteristics consistent with re-activation of EBV infection and significantly (p = 0.02) less secretion of interferon (IFN) gamma from blood CD4 positive T cells. After one month of daily capsules containing 2 x 10(10) colony forming units of L acidophilus, secretion of IFNgamma from T cells had increased significantly (p = 0.01) to levels found in healthy control athletes. A significant (p = 0.03) increase in salivary IFNgamma concentrations in healthy control athletes after the one month course of L acidophilus demonstrated in man the capacity for this probiotic to enhance the mucosal IFNgamma concentration. CONCLUSION: This is the first evidence of a T cell defect in fatigued athletes, and of its reversal following probiotic therapy.

Adolescent↗

Just-in-time tomography (JiTT): a new concept for image-guided radiation therapy.

Soft-tissue target motion is one of the main concerns in high-precision radiation therapy. Cone beam computed tomography (CBCT) has been developed recently to image soft-tissue targets in the treatment room and guide the radiation therapy treatment. However, due to its relatively long image acquisition time the CBCT approach cannot provide images of the target at the instant of the treatment and thus it is not adequate for imaging targets with intrafraction motion. In this note, a new approach for image-guided radiation therapy-just-in-time tomography (JiTT)-is proposed. Differing from CBCT, JiTT takes much less time to generate the needed tomographical, beam's-eye-view images of the treatment target at the right moment to guide the radiation therapy treatment.

Algorithms↗

Evaluation of anti-Helicobacter pylori IgG2 antibody for the diagnosis of Helicobacter pylori infection in western and Chinese populations.

BACKGROUND: The performance of commercial Helicobacter pylori diagnostic kits developed for particular geographic regions has often been found to be of poor diagnostic value when applied to other regions, possibly because of infections being caused by different H. pylori strains in different regions. AIM: To evaluate the performance of an IgG2 anti-H. pylori enzyme-linked immunoassay test (Helirad Alert) for detection of H. pylori infection in both Australian and Hong Kong (Chinese) subjects. METHODS: Serum samples were tested for H. pylori specific IgG2 and IgG antibodies by enzyme-linked immunoassay kits using identical antigen preparation in 168 Australian and 160 Hong Kong (Chinese) subjects diagnosed with dyspepsia. RESULTS: Using a cut-off value determined by analysis of H. pylori-negative Australian samples, the sensitivity, specificity and accuracy of the IgG2 assay were 77.8, 97.4 and 91.1%, respectively, for the Australian samples and 96.3, 83.8 and 90% for Hong Kong samples. For the IgG assay, sensitivity, specificity and accuracy were 87.0, 99.1 and 95.2% for Australian samples and 97.5, 75 and 86.3% for Hong Kong samples respectively. Receiver-operating characteristic analysis showed better discrimination of H. pylori status when the IgG2 assay was applied to Hong Kong samples, while the IgG assay was better in the Australian samples. CONCLUSION: These data demonstrate that the Helirad Alert enzyme-linked immunoassay could provide a reliable method for screening H. pylori infection in both western and Chinese populations.

Adult↗

Enhanced clearance of Candida albicans from the oral cavities of mice following oral administration of Lactobacillus acidophilus.

Orally administered live Lactobacillus acidophilus was assessed for its capacity to enhance clearance from the oral cavity of DBA/2 mice shown previously to be 'infection prone'. L. acidophilus fed to DBA/2 mice significantly shortened the duration of colonization of the oral cavity compared to controls. Enhanced clearance of Candida albicans correlated with both early mRNA gene expression for interleukin (IL)-4 and interferon (IFN)-gamma and expression of their secreted products in cultures of cervical lymph nodes stimulated with Candida antigen. In addition rapid clearance correlated with higher levels of IFN-gamma and nitric oxide in saliva. Delayed clearance, less pronounced levels of the cytokine response, saliva IFN-gamma and nitric oxide, and later mRNA expression for IL-4 and IFN-gamma relative to feeding with the L. acidophilus isolate were noted in mice fed a different Lactobacillus isolate (L. fermentum). These observations indicate significant variations in individual isolates to activate the common mucosal system.

Administration, Oral↗

Development of high quantum efficiency, flat panel, thick detectors for megavoltage x-ray imaging: an experimental study of a single-pixel prototype.

Our overall goal is to develop a new generation of electronic portal imaging devices (EPIDs) with a quantum efficiency (QE) more than an order of magnitude higher and a spatial resolution equivalent to that of EPIDs currently used for portal imaging. A novel design of such a high QE flat-panel based EPID was introduced recently and its feasibility was investigated theoretically [see Pang and Rowlands, Med. Phys. 31, 3004 (2004)]. In this work, we constructed a prototype single-pixel detector based on the novel design. Some fundamental imaging properties including the QE, spatial resolution, and sensitivity of the prototype detector were measured with a 6 MV beam. It has been shown that the experimental results agree well with theoretical predictions and further development based on the novel design including the construction of a prototype area detector is warranted.

Calibration↗

Development of high quantum efficiency, flat panel, thick detectors for megavoltage x-ray imaging: a novel direct-conversion design and its feasibility.

Most electronic portal imaging devices (EPIDs) developed to date, including recently developed flat panel systems, have low x-ray absorption, i.e., low quantum efficiency (QE) of 2%-4% as compared to the theoretical limit of 100%. A significant increase of QE is desirable for applications such as a megavoltage cone-beam computed tomography (MVCT) and megavoltage fluoroscopy. However, the spatial resolution of an imaging system usually decreases significantly with an increase of QE. The key to the success in the design of a high QE detector is therefore to maintain the spatial resolution. Recently, we demonstrated theoretically that it is possible to design a portal imaging detector with both high QE and high resolution [see Pang and Rowlands, Med. Phys. 29, 2274 (2002)]. In this paper, we introduce such a novel design consisting of a large number of microstructured plates (made by, e.g., photolithographic patterning of evaporated or electroplated layers) packed together and aligned with the incident x rays. On each plate, microstrip charge collectors are focused toward the x-ray source to collect charges generated in the ionization medium (e.g., air or gas) surrounded by high-density materials that act as x-ray converters. The collected charges represent the x-ray image and can be read out by various means, including a two-dimensional (2-D) active readout matrix. The QE, spatial resolution, and sensitivity of the detector have been calculated. It has been shown that the new design will have a QE of more than an order of magnitude higher and a spatial resolution equivalent to that of flat panel systems currently used for portal imaging. The new design is also quantum noise limited down to very low doses (approximately 1-2 radiation pulses of the linear accelerator).

Equipment Design↗

Imaging of 1.0-mm-diameter radiopaque markers with megavoltage X-rays: an improved online imaging system.

PURPOSE: To improve an online portal imaging system such that implanted cylindrical gold markers of small diameter (no more than 1.0 mm) can be visualized. These small markers would make the implantation procedure much less traumatic for the patient than the large markers (1.6 mm in diameter), which are usually used today to monitor prostate interfraction motion during radiation therapy. METHODS AND MATERIALS: Several changes have been made to a mirror-video based online imaging system to improve image quality. First, the conventional camera tube was replaced by an avalanche-multiplication-based video tube. This new camera tube has very high gain at the target such that the camera noise, which is one of the main causes of image degradation of online portal imaging systems, was overcome and effectively eliminated. Second, the conventional linear-accelerator (linac) target was replaced with a low atomic number (low-Z) target such that more diagnostic X-rays are present in the megavoltage X-ray beam. Third, the copper plate buildup layer for the phosphor screen was replaced by a thin plastic layer for detection of the diagnostic X-ray components in the beam generated by the low-Z target. RESULTS: Radiopaque fiducial gold markers of different sizes, i.e., 1.0 mm (diameter) x 5 mm (length) and 0.8 mm (diameter) x 3 mm (length), embedded in an Alderson Rando phantom, can be clearly seen on the images acquired with our improved system. These markers could not be seen on images obtained with any commercial system available in our clinic. CONCLUSION: This work demonstrates the visibility of small-diameter radiopaque markers with an improved online portal imaging system. These markers can be easily implanted into the prostate and used to monitor the interfraction motion of the prostate.

Equipment Design↗

Development of high quantum efficiency flat panel detectors for portal imaging: intrinsic spatial resolution.

Recently developed flat panel detectors have been proven to have a much better image quality than conventional electronic portal imaging devices (EPIDs). They are, however, not yet the ideal systems for portal imaging application due to the low x-ray absorption, i.e., low quantum efficiency (QE), which is typically on the order of 2-4% as compared to the theoretical limit of 100%. The QE of current flat panel systems can be improved by significantly increasing the thickness of the energy conversion layer (i.e., amorphous selenium or phosphor screen). This, however, will be at the expense of a decrease in spatial resolution mainly due to x-ray scatter in the conversion layer (and also the spread of optical photons in the case of phosphor screen). In this paper, we investigate theoretically the intrinsic spatial resolution of a high QE flat panel detector with a new energy conversion layer that is much denser and thicker than that of current flat panel systems. The modulation transfer function (MTF) of the system is calculated based on a theoretical model using a novel approach, which uses an analytical expression for absorbed dose. It is found that if appropriate materials are used for the conversion layer, then the intrinsic MTF of the high QE flat panel is better than that of current EPIDs, and in addition they have a high QE (e.g., approximately 60%). Some general rules for the design of the conversion layer to achieve both high QE and high resolution as well as high DQE are also discussed.

Computer Simulation↗

Primary role for CD4(+) T lymphocytes in recovery from oropharyngeal candidiasis.

Oropharyngeal candidiasis is associated with defects in cell-mediated immunity and is commonly seen in human immunodeficiency virus positive individuals and AIDS patients. A model for oral candidiasis in T-cell-deficient BALB/c and CBA/CaH nu/nu mice was established. After inoculation with 10(8) Candida albicans yeasts, these mice displayed increased levels of oral colonization compared to euthymic control mice and developed a chronic oropharyngeal infection. Histopathological examination of nu/nu oral tissues revealed extensive hyphae penetrating the epithelium, with polymorphonuclear leukocyte microabscess formation. Adoptive transfer of either naive or immune lymphocytes into immunodeficient mice resulted in the recovery of these animals from the oral infection. Reconstitution of immunodeficient mice with naive CD4(+) but not CD8(+) T cells significantly decreased oral colonization compared to controls. Interleukin-12 and gamma interferon were detected in the draining lymph nodes of immunodeficient mice following reconstitution with naive lymphocytes. This study demonstrates the direct requirement for T lymphocytes in recovery from oral candidiasis and suggests that this is associated with the production of cytokines by CD4(+) T helper cells.

Adoptive Transfer↗

A therapeutic vaccine for mucosal candidiasis.

Persistent and recurrent infection of mucosal surfaces with Candida albicans is common, ranging from a nuisance to a life threatening clinical problem. No effective prophylactic or therapeutic vaccine has been developed. We have studied a mouse model of oral candida infection to identify regulatory and effector molecules of T cell activation as parameters of induced immunity, and here describe the use of this model to determine an optimal immunisation strategy. Oral immunisation with the blastospore yeast form (but not subcutaneous immunisation) induced clinical immunity, with a shift in parameters of cytokine response characterised by an early and sustained production of both IFN-gamma and IL-4 from antigen-stimulated cervical node T lymphocytes.

Animals↗

Irradiation-induced oral candidiasis in an experimental murine model.

The aim of this experiment was to establish a mouse model of irradiation-induced oral candidiasis and to explore the cellular populations and mechanisms by which the infection is cleared from the oral mucosa. BALB/c mice received irradiation to the head and neck equivalent to 800 Rad using a Cobalt 60 gamma source. Both irradiated and non-irradiated mice were infected orally with 1 x 10(8) Candida albicans yeasts. Compared with untreated controls, irradiated animals developed a more severe infection of longer duration, with hyphae penetrating the oral mucosa. Monoclonal antibody depletion of CD4+ but not CD8+ T cells from the systemic circulation prolonged the infection in irradiated mice, but not in controls. Supernatants of submandibular and superficial cervical lymph node cultures from irradiated animals demonstrated significantly higher titers of interleukin-12, but similar levels of interferon-gamma compared with controls. Screening for cytokine production by an RNase protection assay detected only macrophage migration inhibition factor in irradiated and non-irradiated oral tissues from day 8 onwards. The results of this study demonstrate a requirement for CD4+ T cells in the recovery from oral candidiasis induced by head and neck irradiation in mice, and are consistent with a role for Th1-type cytokines in host resistance.

Analysis of Variance↗

Nitric oxide-enhanced resistance to oral candidiasis.

A murine model of oral candidiasis was used to show that nitric oxide (NO) is involved in host resistance to infection with Candida albicans in infection-'resistant' BALB/c and infection-'prone' DBA/2 mice. Following infection, increased NO production was detected in saliva. Postinfection samples of saliva inhibited the growth of yeast in vitro. Treatment with NG-monomethyl-L-arginine (MMLA), an inhibitor of NO synthesis, led to reduced NO production, which correlated with an increase in C. albicans growth. Reduction in NO production following MMLA treatment correlated with an abrogation of interleukin-4 (IL-4), but not interferon-gamma (IFN-gamma), mRNA gene expression in regional lymph node cells. Down-regulation of IL-4 production was accompanied with an increase in IFN-gamma production in infection-'prone' DBA/2 mice. There was a functional relationship between IL-4 and NO production in that mice treated with anti-IL-4 monoclonal antibody showed a marked inhibition of NO production in saliva and in culture of cervical lymph node cells stimulated with C. albicans antigen. The results support previous conclusions that IL-4 is associated with resistance to oral candidiasis and suggest that NO is involved in controlling colonization of the oral mucosal surface with C. albicans.

Animals↗

Shift of the gastric T-cell response in gastric carcinoma.

BACKGROUND AND AIMS: The etiology and pathophysiology of stomach carcinoma is complex, and the mechanism whereby H. pylori directly or indirectly induces carcinoma remains unclear. In this study, interleukin (IL)-8, IL-4 and interferon (IFN)-gamma were measured in the tissue culture supernatant of gastric organ cultures from subjects with chronic gastritis with or without H. pylori infection, and with or without gastric cancer and gastric dysplasia. RESULTS: Interleukin-8 levels were higher in cancer- and H. pylori-infected gastritis subjects than in H. pylori-negative subjects (12.95 +/- 3.16, 10.48 +/- 1.55 and 4.49 +/- 1.28 ng/mL, respectively). Elevated levels of IFN-gamma were detected in both H. pylori-infected and non-infected subjects with uncomplicated gastritis (72.23 +/- 19.0 and 34.61 +/- 5.30 pg/mL) and in non-infected dysplasia subjects (88 +/- 20.5 pg/mL). Background levels of IL-4 (< or = 9.4 pg/mL) in uncomplicated gastritis subjects and relatively high levels of IL-4 in dysplasia subjects (25.8 +/- 7.3 pg/mL) were detected. In contrast, trace amounts of IFN-gamma (16.01 +/- 0.35 pg/mL) and high levels of IL-4 (42.81 +/- 8.49 pg/mL) in gastric biopsy culture supernatants were found in cancer subjects. Mucosal IL-4 levels (but not IL-8 levels) correlated with infection and mucosal anti-H. pylori immunoglobulin G antibody. CONCLUSIONS: The significant differences between gastritis with and without cancer and dysplasia indicated a shift from a Th1 to a Th2 helper cell pattern of cytokine secretion. This study has identified a local mucosal defect in gastric cancer. The near absence of IFN-gamma production from the mucosa at the margins of the tumor may be a critical factor in promoting growth of neoplastic cells.

Adenocarcinoma↗

Is there another chapter in the Helicobacter pylori/peptic ulcer disease story?

The role of Helicobacter pylori in the production of mucosal damage has largely been considered within a simple infection paradigm, because to date eradication has appeared to be a predictable outcome of antibiotic therapy. Changes in the epidemiology and management of peptic ulcer disease, however, require a more comprehensive framework to understand these shifting clinical patterns. The present review examines mucosal damage as an outcome of a complicated host-parasite relationship, with alterations in both parasite physiology and host defence mechanisms being keys to understanding disease patterns.

Anti-Bacterial Agents↗

Investigation of a direct conversion flat panel imager for portal imaging.

Flat-panel based x-ray imaging is an emerging new technology that could be used to significantly improve the quality of on-line portal imagers. There are two types of flat panel imagers: direct and indirect conversion. Previous experimental work on flat panel detectors for portal imaging application used indirect-conversion imagers. In this paper, a direct-conversion amorphous-selenium flat panel imager is investigated for application in portal imaging. The imager has an active imaging area of 14 in. X 17 in., i.e., 3072 X 2560 pixels each with dimensions 139 microm X 139 microm. The spatial frequency dependent detective quantum efficiency of the imager has been measured for a 6 MV beam and found to be amongst the best area detectors investigated for on-line portal imaging. Effects of changing pixel size, as well as possible improvements to both the image quality and convenience of operation are discussed. Comparison with an indirect conversion flat panel imager is also included.

Diagnostic Imaging↗