Biomedical subjects

T Cheung

Publications and source records attributed to T Cheung.

At least 37 records · Page 2Linked to original sources

PubMed2000

Chemotherapy consisting of doxorubicin, bleomycin, vinblastine, and dacarbazine with granulocyte-colony-stimulating factor in HIV-infected patients with newly diagnosed Hodgkin's disease: a prospective, multi-institutional AIDS clinical trials group study (ACTG 149).

To ascertain the results of standard ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) in HIV-infected patients with newly diagnosed Hodgkin's disease (HD), a nonrandomized, prospective, multiinstitutional clinical trial was conducted by the AIDS Clinical Trials Group (ACTG), in HIV-infected patients with Hodgkin's disease. All patients received the standard ABVD regimen, with granulocyte-colony-stimulating factor (G-CSF). Antiretroviral therapy was not used. Between May, 1992 and August, 1996, 21 patients were added to the study and treated. The median CD4 count was 113 cells/mm3, and 29% had a history of a clinical AIDS-defining condition before diagnosis of HD. Systemic "B" symptoms were present in 90% at diagnosis. Stage IV HD was present in 67%, with bone marrow involvement in 12 (57%). Nodular sclerosis HD was present in 38%, with mixed cellular disease in 31%. Among all patients entered and treated, complete remission (CR) was attained in 9 (43%; 90% confidence interval [CI], 24%-63%), whereas partial response occurred in 4 (19%), leading to an overall objective response rate of 62% (90% CI, 42%-79%). Despite routine use of G-CSF, 10 patients (47.6%) experienced life-threatening neutropenia, with absolute neutrophil counts <500 cells/mm3. In all, nine opportunistic infections occurred in 6 patients (29%) during the study or shortly thereafter. Median survival was 1.5 years. Results of this study suggest that alternative treatment strategies should be explored, including use of chemotherapy together with antiretroviral therapy.

Adult↗

PubMed2000

Assessment of large single-fraction, low-energy X-ray dose with radiochromic film.

PURPOSE: To investigate the accuracy of in vivo dosimetry using radiochromic film for large single-fraction, low-energy irradiations. METHODS AND MATERIALS: Gafchromic MD-55-2 radiochromic film and LiF thermoluminescent dosimeters (TLDs) were placed in vivo on 25 patients to ascertain their effectiveness for assessment of dose. All patients received 10 Gy single fractions at energies ranging from 100 kVp (half-value layer [HVL] = 3.5 mm Al) up to 250 kVp (HVL = 2.3 mm Cu). Effects of small air gaps were also investigated using LiF TLDs and radiochromic film. RESULTS: Radiochromic film adequately measured applied dose for 25 patients in vivo with a standard deviation of 5.5% from prescribed dose. LiF TLDs recorded a standard deviation of 4.1% from measured to applied dose. Small air gaps which can be created under the film or TLDs during in vivo dosimetry were shown to have a measurable but minimal effect on results for gaps less than 5 mm. CONCLUSIONS: Gafchromic film has adequately measured applied dose in vivo at low energy for large 10 Gy single-fraction irradiation.

Fluorides↗

PubMed2000

Light weight concrete: 226Ra, 232Th, 40K contents and dose reduction assessment

Four types of light weight concrete (LWC) commonly used in Hong Kong, namely, autoclave aerated concrete (plus lime), autoclave aerated concrete (plus Pulverized Fuel Ash or PFA), concrete with synthetic aggregate 'Leca' and concrete with polystyrene bean as aggregate were measured for their 226Ra, 232Th and 40K contents using high-resolution gamma spectrometry. All the radionuclide contents except those for the PFA autoclave aerated concrete were below the world averages of building materials. The Ra-equivalents for these four LWC were 49.6, 249, 122 and 44.2 Bq kg(-1), respectively, and were much smaller than a recommended limit of 370 Bq kg(-1) for construction materials for dwellings. The gamma-dose rate for an indoor environment with partition walls built with LWC was estimated to be about 20 x 10(-8) Gy h(-1), which corresponded to a reduction in the effective dose of about 0.25 mSv y(-1) when compared to that obtained for an indoor environment built with normal concrete (NC) only. The Rn exhalation rates from the three lowest Ra-equivalent LWC were calculated as 0.509, 1.28, and 0.335 mBq m(-2) s(-1), respectively, which corresponded to a reduction in the indoor Rn concentration of around 14 Bq m(-3) and reduction in the tracheobronchial dose reaching 1 mSv y(-1) by using the James lung-dosimetry model, when compared to the case of NC.

Journal Article↗

PubMed2000

Blood irradiation with accelerator produced electron beams.

Blood and blood products are irradiated with gamma rays to reduce the risk of graft versus host disease (GVHD). A simple technique using electron beams produced by a medical linear accelerator has been studied to evaluate irradiation of blood and blood products. Variations in applied doses for a single field 20 MeV electron beam are measured in a phantom study. Doses have been verified with ionization chambers and commercial diode detectors. Results show that the blood product volume can be given a relatively homogeneous dose to within 6% using 20 MeV electrons without the need to rotate the blood bags or the beam entry point. The irradiation process takes approximately 6.5 minutes for 30 Gy applied dose to complete as opposed to 12 minutes for a dual field x-ray field irradiation at our centre. Electron beams can be used to satisfactorily irradiate blood and blood products in a minimal amount of time.

Blood↗

PubMed2000

Verification of lung dose in an anthropomorphic phantom calculated by the collapsed cone convolution method.

Verification of calculated lung dose in an anthropomorphic phantom is performed using two dosimetry media. Dosimetry is complicated by factors such as variations in density at slice interfaces and appropriate position on CT scanning slice to accommodate these factors. Dose in lung for a 6 MV and 10 MV anterior-posterior field was calculated with a collapsed cone convolution method using an ADAC Pinnacle, 3D planning system. Up to 5% variations between doses calculated at the centre and near the edge of the 2 cm phantom slice positioned at the beam central axis were seen, due to the composition of each phantom slice. Validation of dose was performed with LiF thermoluminescent dosimeters (TLDs) and X-Omat V radiographic film. Both dosimetry media produced dose results which agreed closely with calculated results nearest their physical positioning in the phantom. The collapsed cone convolution method accurately calculates dose within inhomogeneous lung regions at 6 MV and 10 MV x-ray energy.

Algorithms↗

PubMed2000

Ultraviolet radiation dosimetry with radiochromic film.

Radiochromic film is tested for its broad-band response to ultraviolet (UV) B (290-320 nm) and A (320 nm400 nm), visible and infrared radiation produced by a solar simulator and examined for dosimetry in ultraviolet radiation. Results show that MD-55-2 radiochromic film in solar and fluorescent light sources responds almost exclusively to broad-band UVA radiation with negligible colouration from UVB, visible and low level infrared radiation. A second order polynomial function approximates the change in optical density at 660 nm wavelength for film colouration with exposure to UVA from white light fluorescent and solar UV with exposures measured with a dedicated UVA dosimeter. Using a double exposure technique as used in radiation dosimetry where the film is firstly irradiated to a known UV dose, radiochromic film can be used as a quantitative measure of UVA exposure.

Calibration↗

PubMed1999

Dosimetry of blood irradiation with radiochromic film.

It has been shown that radiochromic film is an ideal dosimeter for assessment and verification of delivered dose to irradiated blood products. Using a parallel opposing two-field technique on a medical linear accelerator, blood is irradiated to diminish the risk of transfusion-associated graft vs. host disease (TA-GVHD). The blood products are irradiated in a Perspex blood box to an applied dose of 29.5-31.7 Gy. Verification of applied dose has been performed with thimble ionization chambers and radiochromic film. Radiochromic film results have matched absorbed dose measurements from ionization chambers at all sites within the 'active' treatment volume within +/-6% for a 95% confidence limit. Using a sample of 100 in-vitro measurements, radiochromic film has measured the average applied dose to blood products to be 30.95+/-2.6 Gy for two standard deviations. Like currently available 'irradiated' film labels, the radiochromic film also serves as a visible reminder that the blood products have been irradiated.

Blood↗

PubMed1998

Evidence for multiclonality in multicentric Kaposi's sarcoma.

Kaposi's sarcoma (KS) develops in a variety of clinical states and is the most common tumor seen in patients with HIV-1 infection. KS develops as a multifocal mucocutaneous disease with subsequent spread to visceral organs, and it has been argued to be a benign proliferation caused by its multifocality at initial presentation, lack of aneuploidy, and spontaneous regression upon withdrawal of immunosuppressive agents in iatrogenically induced disease. We wished to determine whether KS lesions are clonal, indicative of a true neoplasm. Also, we tested whether multifocal KS lesions are clonally related, derived from a common progenitor cell or of independent cellular origin. We studied the X-chromosome inactivation pattern of the human androgen receptor gene in tumor biopsies of women with KS. This procedure tests for the clonality of a tissue specimen, a hallmark of neoplasia. Each specimen was microdissected to minimize normal cell contamination. Of 12 evaluable cases, 10 were HIV-seropositive and 2 were HIV-seronegative. Twenty-four biopsies from the 12 patients were examined. Five cases were consistent with individual KS lesions being clonal. In two cases, multiple KS specimens derived from the individual patients had different androgen receptor alleles inactivated, proving unequivocally that these KS lesions arose independently from distinct transformed cells. In seven cases, only a polyclonal pattern of inactivation was observed, whereas two others had tumor areas of both clonal and polyclonal inactivation patterns. These findings suggest that KS can be a clonal neoplasm, and in some of the cases multiple KS lesions in a given patient can arise from independent cellular origins and acquire clonal characteristics. The polyclonal inactivation pattern observed in other KS lesions may represent a premalignant stage or false negative results.

Adult↗

PubMed1998

Effect of antiviral drugs and hematopoietic growth factors on in vitro erythropoiesis.

BACKGROUND: The purpose of these studies was to improve our understanding of nucleoside analog, antiviral, drug-induced anemia in HIV infection. METHODS: Peripheral blood erythroid progenitor cells (BFU-E) from HIV-positive (HIV+) patients and normal donors were compared in methylcellulose cultures with erythropoietin, with and without antiviral drugs, and with and without the hematopoietic growth factors, stem cell factor (SCF), hemin, and interleukin-3 (IL-3). RESULTS: Normal numbers of BFU-E-derived colonies were observed in cultures from HIV+ patients (mean +/- 1 SD BFU-E/10(5) cells plated: normal = 14.1 +/- 7.9, HIV+ = 17.2 +/- 14.2, p = 0.39). The antiviral drugs zidovudine (AZT), dideoxyinosine (ddI), and didehydrodideoxythymidine (d4T) all inhibited erythroid colonies in HIV+ and normal cultures. AZT was the most erythropoietically inhibitory drug (AZT ID50, mean +/- 1 SD for normal cultures = 2.64 +/- 4.15 microM, for HIV+ cultures = 6.28 +/- 10.79 microM, p = 0.24). Hematologic toxicity was less with ddI and d4T. However, doses of ddI and d4T < or = 10 microM inhibited colony growth in 9/14 and 8/12 cultures, respectively, from HIV+ patients. CONCLUSIONS: Stem cell factor (SCF), hemin, and interleukin-3 (IL-3) increased colony growth in HIV+ and normal cultures. In control cultures, hematopoietic growth factors added singly increased growth 1.3- to 8-fold. Hematopoietic growth factors increased growth even in cultures containing antiviral drugs. In some instances growth factors restored growth to control levels. SCF, hemin, and IL-3 were most effective when combined.

Adult↗

PubMed1997

Treatment of histoplasmosis with fluconazole in patients with acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Acquired Immunodeficiency Syndrome Clinical Trials Group and Mycoses Study Group.

PURPOSE: This study assesses the efficacy and safety of fluconazole therapy in patients with acquired immunodeficiency syndrome (AIDS) and mild to moderately severe manifestations of disseminated histoplasmosis. PATIENTS AND METHODS: This was a multicenter, open-label, nonrandomized prospective trial. All patients had AIDS and disseminated histoplasmosis. Patients were treated with 1,200 mg of fluconazole given by mouth once on the first day, then 600 mg once daily for 8 weeks, and those patients who improved clinically were then assigned fluconazole maintenance therapy 200 mg once daily for at least 1 year. Interim analysis revealed a high failure rate (10 of 20, 50%), causing revision of the protocol to increase the fluconazole dose to 1,600 mg given once on the first day, then 800 mg once daily, and the duration to 12 weeks for induction therapy and then 400 mg daily for 1 year for maintenance therapy. MEASUREMENTS AND MAIN RESULTS: Thirty-six of 49 patients (74%; 95% confidence interval [CI]: 59% to 85%) with mild to moderately severe clinical manifestations who entered into the revised study responded to 800 mg of fluconazole daily for 12 weeks as induction therapy. Of the seven patients who failed induction therapy because of progression of histoplasmosis, one died of the infection. Of 36 patients who entered into the maintenance phase of the study receiving 400 mg of fluconazole daily for 1 year, 11 (30.5%) relapsed, including one who died (2.8%). Two of the 49 patients (4.1%) were removed because of grade 4 adverse events, alkaline phosphatase elevation for one and aspartate aminotransferase elevation in the other. The relapse-free rate at 1 year was 53% (95% CI: 32% to 89%), prompting closure of the study. CONCLUSIONS: Fluconazole 800 mg daily is a safe and moderately effective induction therapy for mild or moderately severe disseminated histoplasmosis in patients with AIDS. On the basis of historic comparison, fluconazole 400 mg daily is less effective than itraconazole 200 to 400 mg daily or amphotericin B 50 mg given weekly as maintenance therapy to prevent relapse.

AIDS-Related Opportunistic Infections↗

PubMed1997

A randomized, double-blind, placebo-controlled trial of cidofovir gel for the treatment of acyclovir-unresponsive mucocutaneous herpes simplex virus infection in patients with AIDS.

The safety and efficacy of cidofovir gel for treatment of acyclovir-unresponsive herpes simplex virus infections in AIDS patients was evaluated in a randomized, double-blind, multicenter trial. Cidofovir (0.3% or 1%) or placebo gel was applied once daily for 5 days. Ten of 20 cidofovir-treated and none of 10 placebo-treated patients had complete healing or >50% decreased area (P = .008); 30% of cidofovir-treated patients versus 0 placebo recipients had complete healing (P = .031). Viral shedding ceased in 13 (87%) of 15 cidofovir-treated and 0 of 9 placebo-treated patients (P = .00004). For cidofovir-treated patients, median time to complete or good response was 21 days, and median time to negative viral culture was 2 days (P = .025, P = .0001, respectively). Median lesion area decreases were 58% for cidofovir-treated versus 0 for placebo-treated patients (P = .005), and mean pain score changes were -1.84 versus -0.34 (P = .042). Application site reactions occurred in 25% of cidofovir-treated and 20% of placebo-treated patients; none was dose-limiting. Cidofovir therapy provided significant benefits in lesion healing, virologic effect, and pain reduction.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 Study Group.

OBJECTIVE: To compare the tolerability and efficacy of three oral regimens for the treatment of patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia. DESIGN: A randomized, double-blind study. SETTING: 24 U.S. academic medical centers. PATIENTS: 181 patients with morphologically confirmed P. carinii pneumonia and alveolar-arterial oxygen differences (PAO2-PaO2) of 45 mm Hg or less. INTERVENTION: Patients were randomly assigned to receive trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for 21 days. Patients with a PAO2-PaO2 of 35 to 45 mm Hg at study entry also received prednisone. MEASUREMENTS: Serial clinical and laboratory evaluations for therapeutic response and toxicity. Therapeutic failure at day 21 was defined by any of the following: increase in PAO2-PaO2 of greater than 20 mm Hg; no remission of baseline signs and symptoms; and change in antipneumocystis therapy for reasons other than toxicity, intubation, or death. Dose-limiting toxicity was defined as discontinuation of therapy by the primary physician because of one or more adverse reactions. RESULTS: No statistically significant differences were seen among treatment groups in the proportions of patients who had dose-limiting toxicity (P=0.2), therapeutic failure (P>0.2), or a complete course of therapy (P>0.2). Survival during therapy or for 2 months thereafter did not differ among the three groups (P>.02). However, elevation of serum aminotransferase levels to more than five times the baseline levels was more frequent in the trimethoprim-sulfamethoxazole group (P=0.003), and one or more serious hematologic toxicities (neutropenia, anemia, thrombocytopenia, or methemoglobinemia) occurred more frequently in the clindamycin-primaquine group (P=0.01). CONCLUSIONS: The rates of dose-limiting toxicity, therapeutic failure, and survival did not differ among patients with AIDS who were receiving oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for mild to moderate P. carinii pneumonia. However, the limited sample size prevents the unequivocal demonstration of the equality of these three regimens. Differences in expected categories of toxicities associated with each regimen should guide the clinician in choosing first-line therapy, particularly for patients with baseline hepatic insufficiency or myelosuppression.

AIDS-Related Opportunistic Infections↗

PubMed1996

The bioconcentration of 131I in fresh water fish.

The dynamic characteristics of the radionuclide concentration process in fresh water fish have been studied. The experimental data for the tilapias were fitted using a simple compartment model to get characteristic parameters such as concentration factors, elimination rate constants, and initial concentration rates, which are 3.08 Bq kg-1/Bq L-1, 0.00573 h-1, and 12.42 Bq kg-1 h-1, respectively. The relative concentrations of 131I in different parts, i.e., head, gills, flesh, bone and internal organs, of the tilapias are also determined, which are found to be 10.8, 15.4, 26.1, 11.0, and 37.0%, respectively. The effects of different factors on the transfer of radionuclides in fresh water fishes are also discussed. Experiments on the tilapias and the common carp show that the variation of concentration factors for different species may be significant even for the same radionuclide and the same ecological system. On the other hand, the variation in the concentration factors for the flesh of the tilapias is not significant for a certain range of 131I concentrations in the water.

Animals↗

PubMed1993

Hypofibrinolysis in patients with hypercoagulability: the roles of urokinase and of plasminogen activator inhibitor.

The prevalence of abnormalities of fibrinolysis in patients with venous thromboembolism is as yet unknown. Defined abnormalities include congenital dysfunction and deficiency of plasminogen, and probably impaired plasminogen activation secondary to elevated levels of plasminogen activator inhibitor type 1 (PAI-1) or to impaired release of tissue plasminogen activator (tPA). In this preliminary study, we analyzed plasma samples from 21 patients for whom an investigation for possible thrombophilia was requested. Twenty of the patients had venous thromboembolism, and one had arterial thrombosis at an early age. Two patients had deficiency of protein C or protein S, but no other recognized biochemical disturbances related to thrombophilia were identified. Patient samples and plasma from 25 normal controls were assayed for tPA activity, PAI-1 activity, and urokinase (uPA) activity and antigen. tPA activity and antigen were not significantly different in patients than in controls. PAI-1 activity was significantly greater in patients (P < 0.0001). uPA activity was not different in the two groups. However, uPA antigen was significantly reduced in patients compared to controls (P = 0.001). These data suggest that hypofibrinolysis leading to a risk of thrombosis may be caused not only by elevated PAI-1 activity but also by reduced total uPA concentration.

Adult↗

PubMed1993

Characterization of radioimmunoassays for high- and low-molecular weight urokinases and estimation of different molecular forms of urokinase in urine and plasma.

Antibody populations against high- and low-molecular weight urokinases (HUK and LUK) were purified by passage of rabbit antiserum immunoglobulin fractions made against HUK and LUK through HUK- or LUK-bound Sepharose 4B (Pharmacia AB, Uppsala, Sweden) gels, respectively. Radioimmunoassays were then set up with these antibody populations. The characteristics of these radioimmunoassays were studied by competition of different antigens against radiolabeled HUK or LUK for these antibodies. We found that the anti-HUK antibody population recognizes epitopes on the light chain of HUK, most of which are situated outside of the urokinase-receptor binding sequence of amino acids. The anti-LUK antibody population probably recognizes a region on LUK distinct from its catalytic site. This region is also present in HUK but is altered in single-chain urokinase, suggesting that a conformation change takes place when single-chain urokinase is converted to HUK. The complexes of HUK and LUK with plasminogen activator inhibitor 1 or 2 could compete in either radioimmunoassay, with different and diminished efficiencies. Taking advantage of this result, we devised a procedure to measure the concentrations of various urokinase species in human urine. We found that freshly voided urine contained substantial amounts of free HUK, some HUK- and LUK-plasminogen activator inhibitor complexes, and a small amount of single-chain urokinase. By using a combination of radioimmunoassay and zymography, we found that human plasma contains mostly HUK-plasminogen activator inhibitor 1 complexes, a small amount of single-chain urokinase or HUK, and no LUK or LUK-inhibitor complexes.

Antibodies↗

PubMed1992

Alzheimer's disease and control brain contain soluble derivatives of the amyloid protein precursor that end within the beta amyloid protein region.

The 39-43 amino acid beta amyloid protein (A beta) that deposits as amyloid in the brains of patients with Alzheimer's disease (AD) is encoded as an internal sequence within a larger membrane-associated protein known as the amyloid protein precursor (APP). In cultured cells, the APP is normally cleaved within the A beta to generate a large secreted derivative and a small membrane-associated fragment. Neither of these derivatives can produce amyloid because neither contains the entire A beta. Our study was designed to determine whether the soluble APP derivatives in human brain end within the A beta as described in cell culture or whether AD brain produces potentially amyloidogenic soluble derivatives that contain the entire A beta. We find that both AD and control brain contain nonamyloidogenic soluble derivatives that end at position 15 of the A beta. We have been unable to detect any soluble derivatives that contain the entire A beta in either the AD or control brain.

Alzheimer Disease↗

PubMed1988

Effect of nutritional zinc-deficiency on O6-alkylguanine-DNA-methyl-transferase activities in rat tissues.

The effect of nutritional zinc-deficiency on the activities of O6-alkylguanine:DNA methyltransferase (AGT) in 9 rat tissues including liver, lung, kidney, spleen, brain, esophagus, forestomach, gastric-stomach and small intestine has been examined. Individual tissue extracts prepared from zinc-deficient and pair-fed, zinc-sufficient rats were incubated with N-[3H]methylnitrosourea-methylated calf thymus DNA for 1 h. The activities of AGT in these tissues were measured by two methods: (a) the transfer of the methyl group from O6-methylguanine in substrate DNA to AGT protein, and (b) the determination of the ratio of O6-methylguanine:7-methylguanine remaining in substrate DNA following incubation. AGT activities (expressed as fmol protein methylated/h per mg protein) were significantly reduced in the esophagus, spleen and lungs of zinc-deficient rats as compared to those in their corresponding zinc-sufficient counterparts. The ratio of O6-methylguanine:7-methylguanine was also reduced in the esophagus of the zinc-deficient rat. These results were consistent with our earlier findings that dietary zinc-deficiency enhances nitrosamine-induced esophageal carcinogenesis in rats.

Animals↗

PubMed1987

Non-cytocidal natural variants of human immunodeficiency virus isolated from AIDS patients with neurological disorders.

To understand the mechanism of HIV-mediated neuropathology five viral isolates were obtained from four AIDS cases with central nervous system manifestations as the primary involvement. The isolates were identified as HIVs by antigenic cross-reactivity and nucleic acid hybridizations to HIV-specific antibodies and DNA probes. The replication and cytopathic properties of these isolates were studied and compared with lymphadenopathy-associated virus (HIVLAV). All isolates had replication competence equivalent to LAV, but four isolates did not kill T4 (CD-4) cells. This isolation of non-cytocidal natural variants of HIV raises the possibility that in some AIDS cases the neurological disorders might be due to HIV variants that are non-cytocidal to T4 cells. The results also indicate that virus replication and cytotoxicity are not always concordant functions in HIV.

Acquired Immunodeficiency Syndrome↗