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Biomedical subjects

Timothy C Lee

Publications and source records attributed to Timothy C Lee.

25 records · Page 2Linked to original sources
PubMed2004

Asymptomatic small bowel intussusception associated with post-transplant lymphoproliferative disease.

A 2-yr-old boy who had undergone orthotopic liver transplantation for biliary atresia 6 months prior presented with generalized lymphadenopathy. Physical exam revealed lymphadenopathy only; the patient had no gastrointestinal signs or symptoms. CT was used to evaluate the patient's lymphadenopathy. The findings were consistent with PTLD, and an incidental intussusception causing small bowel obstruction was found. The intussusception was successfully managed expectantly, and the patient's PTLD responded to administration of rituximab. The etiology, diagnosis and management of intussusception is discussed.

Antibodies, Monoclonal↗
PubMed2004

Lack of cytomegalovirus transmission after pancreatic islet transplantation.

In spite of antiviral prophylaxis, the transmission rate of cytomegalovirus (CMV) after solid organ transplantation remains high. In contrast, CMV transmission has never been reported following pancreatic islet transplantation (PIT). Eleven (seven CMV seronegative, four CMV seropositive) recipients underwent a total of 26 PITs. Following PIT recipients were monitored clinically and tested monthly for CMV antigenemia. Valganciclovir was given to all patients for 100 days after each PIT. Follow-up ranged from 6 to 24 months (median 14.5 months). Pancreatic islet grafts were procured from 18 CMV seropositive and 8 seronegative donors (69% and 31% of donors, respectively). In total there were 6 R+D+, 3 R+D-, 12 R-D+, and 5 R-D-PITs. No patient developed CMV antigenemia or symptoms consistent with CMV infection at any time following PIT. Routine posttransplant testing of PIT recipients demonstrated that neither CMV transmission nor CMV infection occurred after PIT.

Adult↗
PubMed2003

The prevalence and severity of coronary artery calcification on coronary artery computed tomography in black and white subjects.

OBJECTIVES: We studied the relationship between coronary artery calcium (CAC) and race in asymptomatic, active-duty personnel in the Prospective Army Coronary Calcium (PACC) project. BACKGROUND: Valid cardiovascular risk assessments in black Americans using coronary artery computed tomography (coronary CT) require the generalizability of population-based CAC score distributions derived from primarily white patient populations. METHODS: Among 1,000 consecutive participants (mean age, 42 +/- 2 years; range, 40 to 45 years), 999 participants underwent coronary CT and indicated a specific racial affiliation. This included white, non-Hispanic in 699 (69.9%) participants and black, non-Hispanic in 194 (19.4%) participants. Univariate associations between race and cardiovascular risk variables were entered into a logistic regression model for CAC that also controlled for socioeconomic status and education. RESULTS: Coronary artery calcium was nearly twice as prevalent in white (19.2%) than in black participants (10.3%) (p = 0.004). Black individuals had a threefold greater prevalence of hypertension, left ventricular hypertrophy, ST-T-wave abnormalities, and current cigarette smoking. Black subjects also had significantly greater blood pressure, high-density lipoprotein cholesterol, glycosylated hemoglobin, lipoprotein(a) and fibrinogen levels, and lower triglyceride levels and waist girth than white subjects. After adjustment for these differences, and socioeconomic adjusters, black individuals were 39% as likely to have any CAC present (odds ratio, 0.39; 95% confidence interval, 0.20 to 0.78; p = 0.007). CONCLUSIONS: Despite a worse cardiovascular risk profile, black Americans have significantly less CAC than white Americans. The use of coronary CT as an accurate risk prediction tool in black Americans will require ethnic-specific data on the presence and severity of CAC.

Adult↗
PubMed2003

Activation of somatostatin receptor subtype 2 inhibits insulin secretion in the isolated perfused human pancreas.

OBJECTIVES: Five distinct somatostatin receptors (SSTRs) have been cloned, characterized, and designated SSTRs 1-5. The role of these receptors in B-cell signaling has not been well characterized. METHODS: In the current study, the isolated perfused human pancreas model was used to determine the specific effect of 4 different somatostatin receptor agonists on insulin secretion. CONCLUSION: We demonstrated that the SSTR 2 agonist and octreotide significantly suppressed insulin secretion. Furthermore, even during the immunoneutralization of endogenous intrapancreatic somatostatin, the SSTR 2 agonist was able to reverse the effect of somatostatin immunoneutralization by suppressing insulin secretion. These results demonstrate that activation of SSTR 2 suppresses insulin secretion in the isolated perfused human pancreas.

Adolescent↗
PubMedDate not supplied

Use of cytokine polymorphisms and Epstein-Barr virus viral load to predict development of post-transplant lymphoproliferative disorder in paediatric liver transplant recipients.

OBJECTIVE: Currently there are no tests to accurately identify paediatric liver transplant patients at risk for post-transplant lymphoproliferative disorder (PTLD). Herein we describe the use of cytokine polymorphisms and real-time quantitative polymerase chain reaction (qPCR) Epstein-Barr virus (EBV) viral load to identify patients at risk for PTLD development. METHODS: Between 2001 and 2004, approximately 1047 patient samples were collected for qPCR for EBV in 59 patients. EBV viral load was reported in three groups: low EBV (<4,000 copies/microg DNA), high EBV/no PTLD (>4000 copies/microg DNA) and biopsy-proven PTLD. All 59 patients also had cytokine polymorphism genotyping performed for six cytokine polymorphisms (transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha, interleukins (IL)-6, IL-10, IL-2, and interferon (IFN)-gamma) from DNA isolated from peripheral blood mononuclear cells. Positive predictive value (PPV) and negative predictive value (NPV) were calculated using qPCR and cytokine polymorphism results. Data are reported as a mean +/- standard error of the mean. RESULTS: There were 35 males and 24 females with a mean follow-up of 34.9 months. EBV viral load had a PPV and NPV of 29 and 95%, respectively. The low IFN-gamma (A/A) polymorphism was found to be present in 4/6 PTLD patients (67%) and only 17/53 (33%) non-PTLD patients. When the low A/A IFN-gamma polymorphism was combined with EBV viral load for prediction of PTLD, PPV and NPV were 57 and 93%, respectively. DISCUSSION: Use of cytokine genotyping in conjunction with qPCR for EBV viral load can significantly improve the predictive value of diagnostic tests for identification of patients at high risk for PTLD.

Adolescent↗
PubMedDate not supplied

Quantification of a low cellular immune response to aid in identification of pediatric liver transplant recipients at high-risk for EBV infection.

OBJECTIVE: Uncontrolled EBV infection leading to lymphoproliferative disease is a significant cause of morbidity in pediatric orthotopic liver transplant (OLT) recipients. Herein, we describe the use of a novel immune assay, which quantifies the lymphocyte immune response and correlates the value to risk for EBV infection. METHODS: All patient data were prospectively collected between 2003 and 2005. The study included 18 pediatric liver transplant recipients, seven males and 11 females with a mean follow-up of 47 months post-OLT. Patient EBV load was monitored using real-time quantitative PCR (qPCR). The ATP release (ng/mL) of CD3+ lymphocytes after mitogenic stimulation with phytohemagluttinin (PHA; Cylex Corporation) was used to quantitate patient immune response. Patients were stratified by EBV load: low (<1000 copies/microg DNA), medium (1000-4000 copies/microg DNA), and high (>4000 copies/microg DNA). RESULTS: Patients with low EBV loads had a significantly (p < 0.04) stronger immune response to PHA than patients with EBV load >1000 copies/microg DNA. Further analysis demonstrated that patients with ATP level <125 ng/mL had 100% probability of an EBV titer >4000 copies/microg DNA, when compared with 22% if the ATP level was between 125 and 400 ng/mL or only 15% if >400 ng/mL (p < 0.05). When immunosuppression was reduced, we observed an increase of the ATP release that correlated with a decrease of the EBV viral load. CONCLUSION: In conclusion, this study investigates the use of a lymphocyte activation assay to closely measure the immunosuppression status of pediatric liver transplant recipients. Because measurement of EBV DNA load as a single parameter has a poor positive predictive value for development of PTLD, the association of these assays may be of help in the identification of patients at risk for PTLD.

Adenosine Triphosphate↗