Patients with head and neck cancer are at high risk of developing additional second primary tumors in the aerodigestive tract as a result of the field cancerization phenomenon. In this context, the appearance of a new neoplasm often poses a problem in differential diagnosis between recurrence and new primary tumor. Twelve patients with nasopharyngeal carcinoma (NPC) who received radiation therapy for the primary tumor and developed a second epithelial malignancy in the nasal cavity or nasopharynx during the follow-up period are presented in this report. The differentiation between the 2 entities based on the spatiotemporal relations, histological features, and the status of Epstein-Barr virus in tumor lesions are also presented. Our study showed that the epithelial malignancy after NPC having late-onset or prolonged interval (range, 5 to 18 years), different histological patterns (keratinizing squamous cell carcinoma, neuroendocrine carcinoma, or small cell carcinoma) distinct from the primary NPC (differentiated or undifferentiated nonkeratinizing carcinoma), and absence of Epstein-Barr virus, indicate a newly developed tumor rather than recurrent NPC. Our observations showed for the first time that second primary epithelial malignancy developed in the nasal cavity or nasopharynx years after curative therapy for NPC with a prevalence of 0.4% (12/2,794). Wild-type p53 protein was expressed more often in the original NPC (9 of 12) than in the second tumors (4 of 10), but the significance was not statistically significant (P = .2048). Genomic analysis for p53 mutation and in situ hybridization for human papillomavirus showed negative results, indicating that both important molecular events in NPC or head and neck cancer play a small role in this particular type of newly developed second malignant tumor. More studies are warranted for further clarification for the development of second epithelial malignancies in treated NPC patients.

Adult↗

PubMed2000

Segment inertial properties of Chinese adults determined from magnetic resonance imaging.

OBJECTIVE: To improve the simulation of the task of manual materials handling for Chinese laborers, this study estimated the inertial properties of Chinese adults by using magnetic resonance imaging. DESIGN: Magnetic resonance imaging was used as a means of estimating inertial property. Following the estimation of inertial properties for the Chinese subjects, comparison between estimates for Chinese and Caucasian populations was made. BACKGROUND: Estimates of segment inertial properties are frequently based on data and procedures developed from human cadaver studies in which inertial properties have been measured directly. The errors might be derived from the utilization of the Caucasian data were questioned in our previous study on the spinal force prediction of the Chinese subjects during manual lifting. METHODS: Magnetic resonance images were scanned at a 20 mm interval from eight males aged 26 (S.D., 4) years. Tissues were differentiated and verified using adequate intensity thresholds on each slice, and the segmental volume and mass were integrated by slices. The moments of inertia for each segment were then determined about the anatomical axes using the parallel axis theorem.Results. Results showed that our estimates were close to the data derived by Dempster with a slight deviation. Larger percentages of mass were found in the upper arm (4.0%) and thigh (13.6%) than in previous studies. On the other hand, smaller moments of inertia about three axes were noted in the shank. CONCLUSION: Biomechanical modeling of the human body requires accurate prediction of body segment parameters that include measures of volume, mass, center of mass, and moments of inertia. This study suggests the need to estimate the inertial properties of segments from the Chinese population. Application of the data may improve the simulation of the task of manual materials handling for Chinese laborers in the future studies. RELEVANCE: Biomechanical modeling of the human body requires accurate prediction of body segment parameters that include measures of volume, mass, center of mass, and moments of inertia. To obtain the basic data of segment parameters for the Chinese adults, this study was proceeded with the magnetic resonance imaging technique.

Adult↗

PubMed2000

The acute and subchronic toxicity of BRB-I-28, a novel class Ib antiarrhythmic agent, in CD-1 mice.

The acute and subchronic toxic effects of BRB-I-28 (7-benzyl-3-thia-7-azabicyclo[3.3.1]nonane HCl), a novel class Ib antiarrhythmic agent, were investigated in male and female mice. The estimated oral LD(50) for BRB-I-28 was 128 mg/kg (male mice) and 131 mg/kg (female mice). In subchronic oral studies, four groups of mice (15/sex/group/dose) were fed daily with diets containing BRB-I-28 for 90 consecutive days. The equivalent daily doses were approximately 0, 16, 32, 76 (male) and 0, 18, 37, 89 mg/kg (female). All mice survived. Food consumption per day was decreased, but water consumption per day was increased (in a non-dose-dependent manner). However, both mean body weight and mean body weight gain were not significantly changed as were true for hematological and clinical chemistry profiles, except for serum Na(+) concentration (male) and serum K(+) concentration in male and female mice (high dose levels). Hepatocellular necrosis occurred in male and female mice (in a dose-dependent fashion). Renal cortical vacuoles and myocardial necrosis with low numbers of lymphocytic infiltrations were present in female mice (middle and high doses). Lesions in the liver, kidney and heart were mild with (very small) changes in serum biochemical values. These data suggest that BRB-I-28 has limited toxic potential, and coupled with low proarrhythmic and other desirable cardiovascular effects, makes BRB-I-28 worthy of further development.

Animals↗

PubMed2000

Clusterin may be involved in rat liver allograft tolerance.

Little is known about the possible role of complement inhibitors on tolerance induced by liver allografts. Clusterin, which is a plasma glycoprotein, inhibits cytolytic membrane attack complex (MAC) of complement by binding to soluble C5b-7 complex. The role of clusterin in relation to the naturally achieved tolerance in a rat orthotopic liver transplantation (OLT) has not been investigated before. Here we determined the kinetics of clusterin expression at different post-transplantation time points in a tolerogenic model (DA-PVG) where rejection was naturally overcome without any immunosuppressive drugs in comparison with the syngenic OLT model (DA-DA). Peripheral blood and liver tissues were taken from OLT at various post-operative time points. A strong expression of soluble clusterin was observed on post-transplantation day 7, which occurred at the peak of the rejection in this tolerogenic OLT model. The expression of clusterin remained strong even after tolerance was achieved. The intensity of clusterin expression was much stronger when compared with the syngenic OLT (DA-DA) model after OLT. A strong expression of clusterin mRNA was also observed in the tolerogenic model on post-OLT day (POD) 7 and the expression persisted when compared with the syngenic model on post-OLT day 60. Our data have shown that the strongest levels of clusterin during the reaction phase in tolerogenic OLT may be involved in tolerance induction.

Animals↗

PubMed2000

Identification of the indoleamine 2,3-dioxygenase nucleotide sequence in a rat liver transplant model.

A tryptophan catabolizer, indoleamine 2,3-dioxygenase (IDO) is highly expressed in the placenta and plays an essential role in maternal tolerance. Recent data have shown that the administration of an IDO inhibitor blocked not only maternal tolerance but also liver allograft tolerance. However, little is known about the induction of IDO in liver allografts, although a gene specific for tryptophan 2,3-dioxygenase (TDO) is believed to be expressed in the liver. In the present study, we investigated whether IDO is induced in liver allografts. Synthetic oligonucleotide primers based on the mouse IDO cDNA sequence were used to amplify RNA derived from livers of donor, syngeneic or allogeneic OLT rats. RNA encoding IDO was induced in the rat allogeneic liver after orthotopic liver transplantation (OLT), but not in syngeneic OLT. The rat nucleotide sequence of the RT-PCR products obtained from OLT livers revealed identities of 89% homology to the mouse IDO and of 68% to the human IDO. This study demonstrated the presence of RNA encoding IDO in allogeneic OLT livers, which may be involved in the immune response after liver transplantation.

Amino Acid Sequence↗

PubMed2000

Low-dose aspirin for infertile women with thin endometrium receiving intrauterine insemination: a prospective, randomized study.

PURPOSE: The objective was to evaluate the effect of aspirin on infertile women with thin endometrium. METHODS: Patients who had thin endometrium (< or = 8 mm) and intrauterine insemination were divided into the aspirin and nonaspirin groups. Endometrial pattern (trilaminar and nontrilaminar) and thickness, the pulsatility index (PI) and resistance index (RI) of the uterine artery, spiral artery, and ovarian dominant follicles, and pregnancy rates of both groups were measured. RESULTS: A total of 114 and 122 women were included in the aspirin and nonaspirin groups, respectively. There were significantly higher percentages of trilaminar endometrium (46.5% vs. 26.2%) and pregnancy rate (18.4% vs. 9.0%) after aspirin therapy. There was nonsignificant difference in the endometrial thickness, and PI/RI values of the uterine artery, spiral artery, and ovarian dominant follicle between both groups. CONCLUSIONS: Higher pregnancy rate and better endometrial pattern were achieved in patients with thin endometrium after aspirin administration. Aspirin therapy could not significantly increase the endometrial thickness and the resistance of uterine and ovarian flow.

Adult↗

PubMed2000

International sharing of split liver grafts in Asia: initial experience.

The donor shortage problem is particularly serious in Asia and has markedly limited progress in liver transplantation. The increasing demand has, in fact, made it necessary to resort to living donor liver transplantation in both pediatric and adult recipients. Nevertheless, expanding the use of split liver allografts is yet another option to increase the supply. This has a wide potential application on a regional level because most liver transplant programs are still small and may have limited resources in terms of being able to do two transplants in one sitting. The first experience of overseas sharing of split liver grafts in Asia took place in January 1999. The graft was from a 35-yr-old donor from Kaohsiung, Taiwan, who sustained irreversible brain damage in a vehicular accident and had optimal conditions for multiorgan donation. The liver was split ex vivo and the left lateral segment was given to a 3-yr-old girl with biliary atresia at the Chang Gung Memorial Hospital. The extended right lobe split graft was transported to Hong Kong and transplanted into a 51-yr-old male patient with end-stage hepatitis C cirrhosis who was then in a state of acute failure with hepatorenal syndrome. Graft function was excellent in both recipients and the patient from Taiwan was discharged without any complications. Unfortunately, the Hong Kong recipient developed a cerebrovascular accident and required a reoperation for bile leakage from the cut surface of the liver in the early postoperative period. He has made a steady recovery since then; graft function has remained good and his kidneys have recovered. Both patients are currently alive and well 11 months post-transplant. This initial experience of overseas sharing of split liver grafts in Asia demonstrates its feasibility. It has a potentially wide applicability and could lead to the establishment of a formal organ-sharing network in the region. Established competence and mutual trust among the participating liver transplant teams would be essential in perpetuating such a graft-multiplying strategy on an organized basis.

Adult↗

PubMed2000

Telomerase activity in peripheral blood for diagnosis of hepatoma.

BACKGROUND: Telomerase activity may be used as a molecular marker for the detection of circulating hepatoma cells in blood of patients with hepatoma. METHODS: Telomerase activity in peripheral blood from hepatocellular carcinoma (HCC) patients was assessed by using a highly sensitive and non-radioisotope telomerase polymerase chain reaction (PCR) ELISA. Initially, tissue telomerase activity was measured in the hepatoma and non-tumour portions by using PCR ELISA within the same specimen, to compare its sensitivity with the conventional telomeric repeat amplification protocol (TRAP) method. Second, telomerase activity was measured in the peripheral blood obtained from patients with HCC, patients with chronic liver disease and in healthy controls. RESULTS: Of the 17 HCC patients, telomerase activity was found to be positive in 14 (82%) by using TRAP and 15 (88%) by using PCR ELISA, indicating that PCR ELISA is a reliable tool for the measurement of telomerase activity. By using the Telomerase PCR ELISA assay, telomerase activities in the peripheral blood of 20 HCC patients was 1.65 +/- 0.78 units. This was significantly greater than the results obtained for 20 chronic liver disease patients (0.43 +/- 0.36 units) and 20 healthy controls (0.39 +/- 0.14 units; P < 0.0001).When the arbitrary cut-off level was set at 0.7 units (maximum value of healthy controls + 0.1), the positive frequency of telomerase activity was 25% for chronic liver disease and 80% for HCC patients (sensitivity 80%, specificity 75%). Among the HCC patients, high telomerase activity in the peripheral blood was shown at stage III HCC with vascular invasion (2.10 +/- 0.62 units, n = 9). This was significantly higher than patients at stage II of HCC (1.28 +/- 0.72 units, n = 11, without vascular invasion; P = 0.012). CONCLUSION: These results suggest that peripheral blood telomerase activity, which may reflect haematogenous micrometastasis, is potentially a practical diagnostic/predictive marker of HCC.

Biomarkers, Tumor↗