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Leeta Alison Green Khoi Nguyen Bijan Berenji Meera Iyer Eileen Bauer Jorge R Barrio Mohammad Namavari Nagichettiar Satyamurthy Sanjiv S Gambhir 《Journal of nuclear medicine》2004,45(9):1560-1570
Reporter probe 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine (18F-FHBG) and reporter gene mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) have been used for imaging reporter gene expression with PET. Current methods for quantitating the images using the percentage injected dose per gram of tissue do not distinguish between the effects of probe transport and subsequent phosphorylation. We therefore investigated tracer kinetic models for 18F-FHBG dynamic microPET data and noninvasive methods for determining blood time-activity curves in an adenoviral gene delivery model in mice. METHODS: 18F-FHBG (approximately 7.4 MBq [approximately 200 microCi]) was injected into 4 mice; 18F-FHBG concentrations in plasma and whole blood were measured from mouse heart left ventricle (LV) direct sampling. Replication-incompetent adenovirus (0-2 x 10(9) plaque-forming units) with the E1 region deleted (n = 8) or replaced by HSV1-sr39tk (n = 18) was tail-vein injected into mice. Mice were dynamically scanned using microPET (approximately 7.4 MBq [approximately 200 microCi] 18F-FHBG) over 1 h; regions of interest were drawn on images of the heart and liver. Serial whole blood 18F-FHBG concentrations were measured in 6 of the mice by LV sampling, and 1 least-squares ratio of the heart image to the LV time-activity curve was calculated for all 6 mice. For 2 control mice and 9 mice expressing HSV1-sr39tk, heart image (input function) and liver image time-activity curves (tissue curves) were fit to 2- and 3-compartment models using Levenberg-Marquardt nonlinear regression. The models were compared using an F statistic. HSV1-sr39TK enzyme activity was determined from liver samples and compared with model parameter estimates. For another 3 control mice and 6 HSV1-sr39TK-positive mice, the model-predicted relative percentage of metabolites was compared with high-performance liquid chromatography analysis. RESULTS: The ratio of 18F-FHBG in plasma to whole blood was 0.84 +/- 0.05 (mean +/- SE) by 30 s after injection. The least-squares ratio of the heart image time-activity curve to the LV time-activity curve was 0.83 +/- 0.02, consistent with the recovery coefficient for the partial-volume effect (0.81) based on independent measures of heart geometry. A 3-compartment model best described 18F-FHBG kinetics in mice expressing HSV1-sr39tk in the liver; a 2-compartment model best described the kinetics in control mice. The 3-compartment model parameter, k3, correlated well with the HSV1-sr39TK enzyme activity (r2 = 0.88). CONCLUSION: 18F-FHBG equilibrates rapidly between plasma and whole blood in mice. Heart image time-activity curves corrected for partial-volume effects well approximate LV time-activity curves and can be used as input functions for 2- and 3-compartment models. The model parameter k3 from the 3-compartment model can be used as a noninvasive estimate for HSV1-sr39TK reporter protein activity and can predict the relative percentage of metabolites. 相似文献
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Margaret V Ragni Bijan Eghtesad Kimberly W Schlesinger Igor Dvorchik John J Fung 《Liver transplantation》2005,11(11):1425-1430
Despite improved survival after liver transplantation (OLTX) in HIV-positive individuals treated with highly active antiretroviral therapy (HAART), some transplant candidates do not survive to OLTX. To determine if pretransplant outcome is related to severity of liver disease and/or HIV infection, we prospectively evaluated 58 consecutive HIV-positive candidates seen at a single center from 1997-2002. Of the 58, 15 (25.9%) were transplanted, whereas 21 (36.2%) died before OLTX, a median one month of evaluation, with more than half of those (12 of 21, 57.1%) dying from infection. By contrast, of 1,359 HIV-negative candidates, 860 (63.3%) were transplanted, whereas 211 (15.5%) died before OLTX (P < 0.001). The cumulative survival following initial evaluation was significantly shorter among HIV-positive than HIV-negative candidates (880 vs. 1,427 days, P = 0.035, Breslow) but was not related to the initial pretransplant MELD score (16 vs. 15), INR (1.5 vs. 1.5), creatinine (1.3 vs. 1.3 mg/dL), or total bilirubin (6.6 vs. 5.7 mg/dL), respectively, all P > 0.05. Among untransplanted HIV-positive candidates, the 21 who died did not differ from the 22 surviving in initial MELD (15 vs. 13), CD4 (230 vs. 327/microL), HIV load (both < 400 copies/mL), HAART intolerance (10/21, 47.6% vs. 10/22, 45.4%), or HCV infection (16/21, 76.2% vs. 16/22, 72.3%), all P > 0.05. Further, the 21 did not differ from the 15 transplanted in pre-OLTX CD4, HIV load, or MELD score, all P > 0.05. In conclusion, pretransplant survival appears shorter in HIV-positive OLTX candidates and is unrelated to severity of liver or HIV disease. Further study is warranted to determine risk factors for poorer pretransplant outcomes. 相似文献
4.
John Fung Dympna Kelly Zakiyah Kadry Kusum Patel-Tom Bijan Eghtesad 《Liver transplantation》2005,11(3):267-280
Although calcineurin inhibitors (CNIs) remain the mainstay of immunosuppression in liver transplantation (LTX), their long-term toxicity significantly contributes to morbidity and mortality. The elucidation of mechanisms of alloimmunity and leukocyte migration have provided novel targets for immunosuppression development. The toxicities of these agents differ from that of the CNI and act additively or synergistically. CNI avoidance protocols in LTX have not been achieved routinely; however, pilot trials have begun to delineate the limitations and promises of such approaches. CNI-sparing protocols appear to be much more promising in balancing the early need for minimizing rejection while tapering doses and minimizing long-term toxicity. 相似文献
5.
M. Jahangiri M. J. Osborne A. P. Jayatunga J. W. Bradley P. Mitchenere 《Annals of the Royal College of Surgeons of England》1993,75(1):34-37
A retrospective analysis in the form of an audit into the management of infantile hypertrophic pyloric stenosis in a district general hospital has revealed that the results are equivalent to that of published data from specialised units. It is stressed in this study that close co-operation has to be maintained between paediatricians and surgeons in the care of these infants. The diagnosis can be made on clinical grounds in the majority of cases. The operation has to be carried out by experienced surgeons and anaesthetists. The morbidity can be minimised under these circumstances and pyloromyotomy can be performed safely in a district general hospital. 相似文献
6.
Metes D Logar A Rudert WA Zeevi A Woodward J Demetris AJ Abu-Elmagd K Eghtesad B Shapiro R Fung JJ Trucco M Starzl TE Murase N 《Human immunology》2003,64(8):787-795
Passenger leukocytes have been demonstrated to play significant roles in initiating and also regulating immune reactions after organ transplantation. Reliable techniques to detect donor leukocytes in recipients after organ transplantation are essential to analyze the role, function, and behavior of these leukocytes. In this report we describe a simple, reliable method to detect donor cells with low frequencies using peripheral blood samples. Detection of small numbers of major histocompatibility complex (MHC) mismatched cells was first studied using four-color flow cytometry in artificially created cell mixtures. By selecting the CD45(+) population and simultaneous staining with several leukocyte lineage markers (CD3, CD4, CD8, CD56, and CD19), MHC-mismatched leukocytes were consistently detected in cell suspensions prepared from directly stained whole blood samples with a threshold sensitivity as low as 0.1%-0.2%. When the fresh peripheral blood mononuclear cells were separated by conventional Ficoll gradient purification, similar, but slightly lower levels of donor cells were detected. Blood samples obtained 1-5 months after liver, kidney, and intestine transplants revealed that the kind of organ allograft influenced levels and lineage pattern of the circulating donor cells. This procedure provided a simple and reliable method in determining early chimerism in transplant recipients. However, the detection of MHC-mismatched leukocytes of all lineages was much lower when frozen peripheral blood mononuclear cells were used. 相似文献
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Hashaam Akhtar Maham Afridi Samar Akhtar Hamaad Ahmad Sabahat Ali Sundas Khalid Sajid Mahmood Awan Shahzaib Jahangiri Yousef Saleh Khader 《JMIR Public Health and Surveillance》2021,7(5)
The COVID-19 outbreak started as pneumonia in December 2019 in Wuhan, China. The subsequent pandemic was declared as the sixth public health emergency of international concern on January 30, 2020, by the World Health Organization. Pakistan could be a potential hotspot for COVID-19 owing to its high population of 204.65 million and its struggling health care and economic systems. Pakistan was able to tackle the challenge with relatively mild repercussions. The present analysis has been conducted to highlight the situation of the disease in Pakistan in 2020 and the measures taken by various stakeholders coupled with support from the community to abate the risk of catastrophic spread of the virus. 相似文献
9.
Soheila Siroosbakht Sadra Rezakhaniha Farshad Namdari Bijan Rezakhaniha 《Andrologia》2021,53(10):e14200
There are conflicting results about uric acid (UA) effect on the prostate. We investigated the relationship between UA and PSA, free PSA, prostate volume and international prostate symptoms score (IPSS) in benign prostate hyperplasia (BPH). This study was conducted in BPH men without cancer who were referred for annual health workup (N = 910) from 2017 to 2020. The mean ages were 67.28 ± 9.2 years. UA was positively related to IPSS and PSA (r = 0.210, p = .023 and r = 0.156, p = .041 respectively) and also negatively related to free/total PSA ratio (r = −0.332, p = .01) but not related to prostate volume (r = 0.036, p = .696). After adjustment for age, BMI and prostate volume, there were significant relationships between hyperuricaemia and PSA, free/total PSA ratio, and IPSS (95% CI: 0.254–1.645, OR = 0.647, p = .039; 95% CI: 0.076–0.899, OR = 0.270, p = .033 and 95% CI: 1.011–3.386, OR = 1.851, p = .038 respectively). These results should be considered during the general assessment of the patients with BPH. The findings raise the possible hypothesis of relationship between serum UA with IPSS and PSA which should be investigated by future studies. 相似文献
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