Analysis of synthetic electron cyclotron emission from the high field side of HL-2M tokamak plasmas.

A synthetic electron cyclotron emission (ECE) diagnostic is used to interpret ECE signals from preset plasma equilibrium profiles, including magnetic field, electron density, and electron temperature. According to the simulation results, the electron temperature (Te) profile covering the harmonic overlap region can be obtained by receiving ECE signals at the high field side (HFS) of the HL-2M plasma. The third harmonic ECE at the low field side (LFS) cannot pass through the second harmonic resonance layer at the HFS unless the optical thickness (τ) of the second harmonic becomes gray (τ ≤ 2). In addition, the impact of the relativistic frequency down-shift has been evaluated and corrected. The measurable range of the HFS ECE has been calculated by scanning different parameters (electron density, temperature, and magnetic field). Higher plasma parameters allow a wider radial range of electron temperature measurements. The minimum inner measurable position can reach R = 120 cm (r/a = -0.89) when the product of core temperature (Te0) and density (ne0) is greater than 35 × 1019 keV m-3, which is extended by more than 30 cm inward compared with that of the LFS measurement. The HFS ECE will greatly improve the diagnostic ability of ECE systems on the HL-2M tokamak.

Fate and removal of antimony in response to stringent control activities after a mine tailing spill.

When tailing spill accidents occur, the risk of contamination by antimony (Sb) tailings into adjacent rivers, sediments, aquifers and soil environments is high. The Sb concentrations in water and sediment under different stringent control activities were investigated for 60 days in the Jialing River basin after a tailing spill accident. Both reservoir regulation and the construction of a temporary dam with coagulation dosing remarkably reduced the Sb levels in the river water. The increase in dissolved Sb caused by the spill was reduced from ~400 µg/L in the inflow to ~200 µg/L in the outflow by reservoir regulation. Moreover, reservoir regulation led to a high concentration of Sb in the reservoir sediment, which was difficult to remove and may cause subsequent unpredictable long-term ecological and health risks. In contrast, the Sb-enriched deposition inside the temporary dam was convenient to remove. Notably, temperature alternations between day and night in winter resulted in a large fluctuation in coagulation efficiency, which may cause the failure of stringent control projects. The results of this study suggest potential improvements to stringent control activities after mine tailing accidents to mitigate environmental impacts and prevent secondary risks.

Saurogobio punctatus sp. nov., a new cyprinid gudgeon (Teleostei: Cypriniformes) from the Yangtze River, based on both morphological and molecular data.

A new cyprinid gudgeon, Saurogobio punctatus sp. nov., is described based on specimens collected from the Yangtze River, China. The new species can be distinguished from its congeners by differences in both morphology and the cytochrome b (cytb) gene sequence. Numerous minute blackish spots are scattered on dorsal and caudal fins in S. punctatus sp. nov. v. absent in the other seven valid Saurogobio species. The new species can be further distinguished from its congeners by the following unique combination of characters: a dorsal fin with eight branched rays; absence of scales in chest area before pectoral origin; upper and lower lips thick, covered with papillae; and a papillose mental pad approximately triangular. Morphologically, the new species most resembles the Chinese lizard gudgeon Saurogobio dabryi, but the new species lays yellowish adhesive eggs v. white pelagic eggs in S. dabryi. A phylogenetic analysis of all Saurogobio species based on cytb gene sequences indicated that S. punctatus sp. nov was distinctly separated from its congeners, with mean sequence divergence ranging from 12·6 to 21·0%. Therefore, molecular data further supported the distinctiveness of the new species.

[Early diagnosis and early treatment for liver cancer in Qidong: survival of patients and effectiveness of screening].

Objective: To evaluate the patients' survival and effectiveness of the live cancer screening for population at high risk for liver cancer in Qidong. Methods: According to the Expert Scheme proposed the Expert Committee of Early Detection and Early Treatment, China Cancer Foundation, diagnostical screening by using combined methods of alpha-fetoprotein and B ultrasound monitoring were carried out biannually in individuals with positive HBsAg who were screened from Qidong area. The evaluation indices of the effectiveness are task completion rate of screening, detection rate of liver cancer, early diagnosis rate, and treatment rate. The deadline of the follow-up for the surviving outcome was March 31, 2016. The life-table method was used to calculate the observed survival, and to make comparison and significant tests between survival rates in Group A (those found via repeated periodic screening) and Group B (those diagnosed without periodic screening). Results: Since 2007, 38 016 target population have been screened, and 3 703(9.74%) individuals with positive HBsAg were found. Except for 29 patients with liver cancer at the initial screening, 3 674 persons in the cohort were followed up; 268 patients with liver cancer were detected from the 33 199 person-times screening, with an annual detection rate of 1.61%. Of them, 186 patients were found in Group A(1.12%), in which 149 patients were the early cases, with an early detection rate of 80.11%; 167 out of 186(89.78%) patients received treatment after diagnosis. The incidence of liver cancer in this HBsAg (+ ) cohort of 25 452 person-years was 1 052.96 per 100 000 annually, 187 cases in males(1 488.45/100 000)and 81 cases in females(628.46/100 000). The 1-, 3-, 5-, and 8-year survival of all patients with liver cancer were 64.55%, 40.50%, 32.54%, and 19.65%, respectively. The 1-, 3-, 5-, and 8-year survival rates were 77.16%, 49.04%, 38.53%, and 24.25% in Group A, and were 36.25%, 21.21%, 21.21%, and 0% in Group B, respectively, with significant differences between two groups (P<0.05). Conclusion: The findings show that screening of individuals at high-risk of development of liver cancer, with semiannual AFP and B ultrasound, according to the Expert Scheme, is effective not only in increasing detection rate but also in detecting liver cancer at early stage, and in improving patients' survival as well.

Molecular cloning and expression vector construction of bovine TRIM28.

The bovine TRIM28 gene was amplified from ovary tissue by using RT-PCR. The TRIM28 gene was inserted into the eukaryotic expression vector pIRES2-EGFP and transfected into bovine fetal fibroblasts by using Lipofectamine 3000. TRIM28 mRNA and protein were detected by fluorescence microscope and western blotting. The results showed that the full length of TRIM28 was cloned and pIRES2-EGFP-TRIM28 was constructed successfully. EGFP expression was observed, and the pIRES2-EGFP-TRIM28 transfected group expressed more TRIM28 protein than that by the pIRES2-EGFP group. The TIMR28 gene has been successfully transferred into bovine fetal fibroblasts.

Renal Transplantation With Final Allocation Based on the Virtual Crossmatch.

Solid phase immunoassays (SPI) are now routinely used to detect HLA antibodies. However, the flow cytometric crossmatch (FCXM) remains the established method for assessing final donor-recipient compatibility. Since 2005 we have followed a protocol whereby the final allocation decision for renal transplantation is based on SPI (not the FCXM). Here we report long-term graft outcomes for 508 consecutive kidney transplants using this protocol. All recipients were negative for donor-specific antibody by SPI. Primary outcomes are graft survival and incidence of acute rejection within 1 year (AR <1 year) for FCXM+ (n = 54) and FCXM- (n = 454) recipients. Median follow-up is 7.1 years. FCXM+ recipients were significantly different from FCXM- recipients for the following risk factors: living donor (24% vs. 39%, p = 0.03), duration of dialysis (31.0 months vs. 13.5 months, p = 0.008), retransplants (17% vs. 7.3%, p = 0.04), % sensitized (63% vs. 19%, p = 0.001), and PRA >80% (20% vs. 4.8%, p = 0.001). Despite these differences, 5-year actual graft survival rates are 87% and 84%, respectively. AR <1 year occurred in 13% FCXM+ and 12% FCXM- recipients. Crossmatch status was not associated with graft outcomes in any univariate or multivariate model. Renal transplantation can be performed successfully, using SPI as the definitive test for donor-recipient compatibility.

Spatial distribution and temporal onset of NF-kB activation and inducible nitric oxide synthase within pancreatic islets in the pre-diabetic stage of genetic, diabetic-prone BB rats: attenuation by drug intervention decreases inflammatory cell infiltration and incidence of diabetes.

OBJECTIVE AND DESIGN: To document in vivo immunolocalization and activation of nuclear factor-kappaB (NF-kappaB) and inducible nitric oxide synthase (iNOS) expression in prediabetic stages of diabetes mellitus. MATERIAL OR SUBJECTS: Genetic, diabetic-prone or diabetic-resistant BB rats (total = 189). TREATMENT: Various doses of an oral dithiocarbamate derivative, NOX-700, or cyclosporine (2.5 mg/kg) starting at 30 or 60 days of age. METHODS: Immunohistochemistry, electrophoretic mobility shift assays, plasma glucose. RESULTS: NF-kappaB and iNOS was increased in pancreas of hyperglycemic, diabetic-prone rats but not normoglycemic, diabetic-resistant rats. Immunostaining for NF-kappaB and iNOS was largely confined to islets and occurred in diabetic-prone rats prior to overt hyperglycemia. NOX-700 decreased cell infiltration, delayed the onset of disease and decreased the incidence of hyperglycemia to levels achieved by immunosuppressant therapy. NOX-700 also decreased the intensity of immunoreactive NF-kappaB and iNOS within pancreatic islets. CONCLUSIONS: These studies support a role of NF-kB and iNOS in diabetogenesis in vivo.

Screening for liver cancer: results of a randomised controlled trial in Qidong, China.

OBJECTIVES: To investigate the effectiveness of screening for liver cancer in reducing mortality from the disease in a high-risk population in China. SETTING: A randomised controlled trial was carried out among men aged 30-69 who were chronic carriers of hepatitis-B virus (HBsAg positive) during the period 1989-1995 in Qidong county, Jiangsu Province, China. METHODS: 5581 HBsAg carriers were identified by population screening and randomly assigned to a screening group (group A, 3712 men), and controls (group B, 1869 men). Screening was planned to be six monthly alpha-fetoprotein (AFP) assays, with follow-up of subjects having an abnormal (>/=20 micrograms/l) test. All subjects were followed up for liver cancer and/or death until 31 December 1995. RESULTS: The overall sensitivity and specificity of the programme was 55.3% and 86.5%, respectively; in subjects who complied with all scheduled screening tests, the values were 80.0% and 80.9%. Three hundred and seventy-four primary liver cancer (PLC) cases were diagnosed. The percentage of cases in stage I was significantly higher in group A (29.6%) than in group B (6.0%). The one-, three-, and five-year relative survival rates were 23.7%, 7.0%, and 4.0% in group A, and 9.7%, 4.0%, and 4.1% in group B respectively, with no difference in five-year survival between the groups. The mortality rate in the screened group (1138 per 100,000 person-years) was not significantly different from that in the controls (1114 per 100,000). A Poisson regression model showed that the probability of death (rate ratio) in the screening group was 0.83 (95% CI 0.68-1.03) relative to the control group. CONCLUSIONS: Screening with AFP resulted in earlier diagnosis of liver cancer, but the gain in lead time did not result in any overall reduction in mortality, because therapy for the patients found by screening was ineffective. Further studies using improved methods of screening, diagnosis and treatment are indicated.

Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer.

Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part from consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semisynthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models by blocking carcinogen bioavailability. In a randomized, double-blind, placebo-controlled chemoprevention trial, we tested whether chlorophyllin could alter the disposition of aflatoxin. One hundred and eighty healthy adults from Qidong were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times a day for 4 months. The primary endpoint was modulation of levels of aflatoxin-N(7)-guanine adducts in urine samples collected 3 months into the intervention measured by using sequential immunoaffinity chromatography and liquid chromatography-electrospray mass spectrometry. This aflatoxin-DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated levels are associated with increased risk of liver cancer. Adherence to the study protocol was outstanding, and no adverse events were reported. Aflatoxin-N(7)-guanine could be detected in 105 of 169 available samples. Chlorophyllin consumption at each meal led to an overall 55% reduction (P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo. Thus, prophylactic interventions with chlorophyllin or supplementation of diets with foods rich in chlorophylls may represent practical means to prevent the development of hepatocellular carcinoma or other environmentally induced cancers.

Oltipraz chemoprevention trial in Qidong, People's Republic of China: results of urine genotoxicity assays as related to smoking habits.

A Phase II chemoprevention trial was carried out in Qidong, Jiangsu Province, People's Republic of China. The recruited subjects, all of whom were positive for serum aflatoxin-albumin adducts, were divided into three treatment arms: placebo; oltipraz ([5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione]) given daily at 125 mg p.o.; and oltipraz given once per week at 500 mg p.o. Besides biomarkers related to aflatoxin B(1) exposure, the genotoxicity of blind-coded urine XAD-2 concentrates was evaluated in 201 subjects on the fifth and seventh week of intervention. Genotoxicity was assessed both in the Ames reversion test in strain YG1024 of Salmonella typhimurium, in the presence of an exogenous metabolic system (S9 mix), with or without beta-glucuronidase, and in a DNA repair test in Escherichia coli. Heating of concentrated urine samples or of cigarette smoke condensates was discovered to result in a significant enhancement of their mutagenicity. It was also found that the mutagenicity of condensates from the most extensively used brands of cigarettes in Qidong was much lower than that of Western cigarette brands. Urine mutagenicity was unrelated to treatment with oltipraz, intervention time, gender, and supplement of S9 mix with beta-glucuronidase. Mutagenicity was significantly but variably higher in cigarette smokers than in nonsmokers, which suggests that the urinary excretion of mutagens in the examined population was not exclusively attributable to smoking. Nevertheless, within smokers (28% of the recruited subjects; 67% of all males), the mutagenic potency was significantly correlated with the self-reported number of cigarettes smoked per day and, even more sharply, with the cotinine concentrations in urines. In conclusion, this study demonstrated the validity of urine mutagenicity assays as a biomarker of tobacco smoke exposure that can be investigated on a relatively large scale in chemoprevention trials and provided evidence that oltipraz treatment had no influence on this parameter in the examined population.

Subtotal parathyroidectomy in renal failure: still needed after all these years.

There are scant data on the frequency of parathyroidectomy (PTX) for end-stage renal disease (ESRD). Medical therapy for ESRD and secondary hyperparathyroidism has evolved to include better dialytic urea removal and the use of calcitriol. The aim of this study was to determine whether medical therapy has changed the frequency or indications for PTX in the management of renal failure. Hospital and clinic records were analyzed to gather information on all patients undergoing PTX for secondary hyperparathyroidism (2HPT) (n = 48) and tertiary hyperparathyroidism (3HPT) (n = 26) from 1986 through 1998 at our institution. Prospective computer databases were queried for information concerning both chronic dialysis and renal transplant patients at our center. The patients were divided based on date of operation before or after 1991, a divider that separated the patients into groups before or after the widespread adoption of intravenous calcitriol treatment during hemodialysis at our institution. Over the 12 year period, the proportion of our chronic dialysis patients undergoing PTX did not change significantly, ranging from 0% to 2.5% per year. Comparing all patients undergoing PTX for 2HPT during 1986-1991 versus 1992-1998, there was no significant difference in time on dialysis [7.0 +/- 4.2 (n = 11) vs. 7.5 +/- 4.6 (n = 36) years, mean +/- SD]. The later group had higher intact parathyroid hormone (iPTH) levels [765 +/- 415 (n = 6) vs. 1377 +/- 636 (n = 28) pg/ml; p = 0.03], lower serum calcium [11.2 +/- 1.0 (n = 12) vs. 9.9 +/- 1.5 (n = 34) mg/dl; p = 0.006], and higher serum phosphate [5.7 +/- 1.6 (n = 12) vs. 7.2 +/- 2.3 (n = 31) mg/dl; p = 0.042]. Among the population of patients with transplants undergoing PTX for 3HPT, the average percent per year undergoing PTX ranged from 0% to 4.2% and did not change during the study period. Comparing the 1986-1991 group to the 1992-1998 group, the time from transplantation to PTX did not change during the study period (3.3 +/- 2.3 vs. 2.9 +/- 3.0 years; p = 0.391), and there were no significant differences between preoperative calcium levels or iPTH levels. Despite advances in dialysis technique and pharmacologic therapy, there has been no change in the proportion of dialysis patients requiring PTX for 2HPT or 3HPT. There was also no change in the time on dialysis for patients with 2HPT or the time from transplant to PTX for patients with 3HPT. Analysis of preoperative biochemical markers as evidence of disease severity suggests there was no change in indications for PTX during our study. From this information we conclude that parathyroid pathophysiology is incompletely understood and medical therapy is not optimal, resulting in a continuing need for PTX in some patients.

Specific p53 mutations detected in plasma and tumors of hepatocellular carcinoma patients by electrospray ionization mass spectrometry.

Hepatocellular carcinoma (HCC), a common cause of cancer deaths worldwide, has several major etiological risk factors, including infection with the hepatitis viruses and exposure to aflatoxin B1. A specific missense mutation resulting from a guanine to thymine transversion at the third position of codon 249 in the p53 tumor suppressor gene has been reported in 10-70% of HCCs from areas of high dietary exposure to aflatoxin B1. Short oligonucleotide mass analysis was compared with DNA sequencing in 25 HCC samples for specific p53 mutations. Mutations were detected in 10 samples by short oligonucleotide mass analysis in agreement with DNA sequencing. Analysis of another 20 plasma and tumor pairs showed 11 tumors containing the specific mutation, and this change was detected in six of the paired plasma samples. Four of the plasma samples had detectable levels of the mutation; however, the tumors were negative, suggesting possible multiple independent HCCs. Ten plasma samples from healthy individuals were all negative. This molecular diagnostic technique has implications for prevention trials and for the early diagnosis of HCC.

Effects of intestinal transplantation on postprandial motility and regulation of intestinal transit.

BACKGROUND: The effects of intestinal transplantation on gut motility have not been completely defined. In this study we examine the effects of ileal transplantation on ileal smooth muscle contractility, together with gastroduodenal emptying, intestinal flow, and transit rates in a canine model of short-gut syndrome. METHODS: Animals (n = 22) were instrumented with strain gauge transducers, collection cannulae, and infusion catheters to assess motility, intestinal flow and transit rates, and gastroduodenal emptying. Ten animals served to define normal parameters. Six animals underwent a 70% resection of the proximal small intestine to serve as short-gut controls. Six animals underwent removal of a 100-cm segment of the ileum, with cold storage, and autotransplantation the following day combined with a 70% resection of proximal bowel. RESULTS: Transplant animals exhibited delayed gastroduodenal emptying, reduced intestinal flow rates, and postprandial phasic contractions that were similar to short-gut controls. However, transplant animals experienced rapid intestinal transit compared with short-gut controls (4.8 +/- 0.4 cm/min vs 2.0 +/- 0.3 cm/min; mean +/- SEM; P <.05). CONCLUSIONS: The transplanted intestine, even with 18 hours of cold storage, exhibits a relatively normal postprandial motor response. However, adaptive responses of the transplanted intestine, such as regulation of intestine transit, may be impaired by neuromuscular injury associated with denervation or ischemia.

p21WAF1 expression is associated with improved survival after adjuvant chemoradiation for pancreatic cancer.

BACKGROUND: Cell cycle arrest after DNA damage is partly mediated through the transcriptional activation of p21(WAF1) by the p53 tumor suppressor gene. p21(WAF1) and p53 are both critical in maintaining cell cycle control in response to DNA damage from radiation or chemotherapy. Therefore, we examined the role of p21(WAF1) and p53 in the determination of outcome for patients who receive radiation and/or chemotherapy for pancreatic cancer. METHODS: p21(WAF1) and p53 protein expression were determined (with the use of immunohistochemistry) in specimens from 90 patients with pancreatic cancer. Forty-four patients underwent surgical resection, and 46 patients had either locally unresectable tumors (n = 9 patients) or distant metastases (n = 37 patients). Seventy-three percent of the patients who underwent resection and 63% of the patients who did not undergo resection received radiation and/or chemotherapy. RESULTS: p21(WAF1) expression was present in 48 of 86 tumors (56%) and was significantly (P<.05) associated with advanced tumor stage. Median survival among patients with resected pancreatic cancer who received adjuvant chemoradiation with p21(WAF1)-positive tumors was significantly longer than in patients with no p21(WAF1) staining (25 vs. 11 months; P = .01). Fifty of 89 tumors (56%) stained positive for p53 protein. p53 overexpression was associated with decreased survival in patients who did not undergo resection. CONCLUSIONS: Normal p21(WAF1) expression may be necessary for a beneficial response to current adjuvant chemoradiation protocols for pancreatic cancer. Alternate strategies for adjuvant therapy should be explored for patients with pancreatic cancer who lack functional p21(WAF1).

Elevated HPRT mutation frequencies in aflatoxin-exposed residents of daxin, Qidong county, People's Republic of China.

Molecular biomarkers are becoming increasingly important tools to identify people who are at highest risk of developing cancer. For many years we have been studying residents of Qidong County, People's Republic of China, to examine the combined impact of aflatoxin exposure with other risk factors as contributors to the high liver cancer incidence rates in this region. This study was conducted to determine the effects of aflatoxin exposure, as measured by serum aflatoxin-albumin adduct levels, on somatic mutation frequency in the human hypoxanthine guanine phosphoribosyl transferase gene (HPRT). Subjects were assigned as low or high according to a dichotomization around the population mean of aflatoxin-albumin adducts. HPRT mutant frequency was determined in individuals by a T cell clonal assay and the samples were categorized as low or high according to mean values. Separate analyses were also conducted for the small set of hepatitis B virus surface antigen (HBsAg)-positive and the larger set of HBsAg-negative individuals, known risk factors for liver cancer. An odds ratio of 19.3 (95% confidence interval 2.0, 183) was demonstrated for a high HPRT mutation frequency in individuals with high aflatoxin exposure compared with those with low aflatoxin exposure. This association indicates that aflatoxin-induced DNA damage in T lymphocytes, assessed using the validated surrogate albumin adduct markers, leads to increased mutations reflected as elevated HPRT gene mutations. This cross-sectional study suggests the potential use of mutation frequency of the HPRT gene as a long-term biomarker of aflatoxin exposure in high risk populations.

Predicting metastasis of pheochromocytomas using DNA flow cytometry and immunohistochemical markers of cell proliferation: A positive correlation between MIB-1 staining and malignant tumor behavior.

BACKGROUND: In the absence of metastases, there are no reliable microscopic features that distinguish malignant from benign pheochromocytomas. Because a common feature of malignancy is the loss of cell cycle regulation and normal growth arrest, the authors hypothesized that analysis of the cell cycle could be used to aid in the diagnosis of malignant pheochromocytoma. METHODS: Cell cycle analysis of archival samples of 51 pheochromocytomas (40 sporadic, 11 familial) from 45 patients, including 6 malignant and 45 benign tumors, was conducted. Flow cytometry data and immunohistochemistry for markers of cell proliferation (proliferating cell nuclear antigen [PCNA] and MIB-1 [Ki-67]) were correlated with the authors' clinical data base records, with a mean follow-up of 66 months. RESULTS: No correlation of DNA ploidy, S-phase fraction by flow cytometry, or PCNA with malignancy was observed. Staining for the MIB-1 nuclear proliferation marker was positive in 3 of 6 (50%) of the malignant pheochromocytomas and negative in all 45 benign tumors (P< 0.01). CONCLUSIONS: Contrary to some previous reports, a diploid DNA pattern does not necessarily predict benign behavior of pheochromocytoma. In this study, cell cycle analysis and, in particular, assessment of the MIB-1 nuclear proliferation marker was useful in the histologic evaluation of pheochromocytoma, as MIB-1 was expressed only in malignant tumors.

Protective alterations in phase 1 and 2 metabolism of aflatoxin B1 by oltipraz in residents of Qidong, People's Republic of China.

BACKGROUND: Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part due to consumption of foods contaminated with aflatoxins, which require metabolic activation to become carcinogenic. In a randomized, placebo-controlled, double-blind phase IIa chemoprevention trial, we tested oltipraz, an antischistosomal drug that has been shown to be a potent and effective inhibitor of aflatoxin-induced hepatocarcinogenesis in animal models. METHODS: In 1995, 234 adults from Qidong were enrolled. Healthy eligible individuals were randomly assigned to receive by mouth 125 mg oltipraz daily, 500 mg oltipraz weekly, or a placebo. Sequential immunoaffinity chromatography and liquid chromatography coupled to mass spectrometry or to fluorescence detection were used to identify and quantify phase 1 and phase 2 metabolites of aflatoxin B1 in the urine of study participants. Reported P values are two-sided. RESULTS: One month of weekly administration of 500 mg oltipraz led to a 51% decrease in median levels of the phase 1 metabolite aflatoxin M1 excreted in urine compared with administration of a placebo (P = .030), but it had no effect on levels of a phase 2 metabolite, aflatoxin-mercapturic acid (P = .871). By contrast, daily intervention with 125 mg oltipraz led to a 2.6-fold increase in median aflatoxin-mercapturic acid excretion (P = .017) but had no effect on excreted aflatoxin M1 levels (P = .682). CONCLUSIONS: Intermittent, high-dose oltipraz inhibited phase 1 activation of aflatoxins, and sustained low-dose oltipraz increased phase 2 conjugation of aflatoxin, yielding higher levels of aflatoxin-mercapturic acid. While both mechanisms can contribute to protection, this study highlights the feasibility of inducing phase 2 enzymes as a chemopreventive strategy in humans.

Molecular metastases in stage I pancreatic cancer: improved survival with adjuvant chemoradiation.

BACKGROUND: Reports of improved survival rates for patients with resected adenocarcinoma of the pancreas coincide with the adoption of adjuvant chemoradiation protocols. The impact of nodal micrometastases demonstrated by molecular assays and adjuvant therapy on survival of patients with stage I pancreatic cancer has not been adequately assessed. METHODS: A retrospective analysis of postoperative chemoradiation on survival in 61 patients undergoing resection of pancreatic adenocarcinomas from 1984 to 1997 was performed. Archival tumors and regional nodes from 25 patients with stage I cancers were tested for a Kiras oncogene mutation using polymerase chain reaction and analysis for restriction fragment length polymorphisms (PCR/RFLP). RESULTS: Adjuvant chemoradiation was associated with improved survival for stage I (P < .01), but not stage III, disease. Seventeen (68%) of 25 patients with stage I disease tested had evidence of mutant Kiras in one or more regional nodes. Survival did not differ for patients with molecular micrometastases. Six of 17 (35%) patients with micrometastases received adjuvant chemoradiation and had improved survival (P < .05). CONCLUSIONS: The majority of patients with stage I pancreatic cancer have PCR/RFLP evidence of lymph node micrometastases. Adjuvant chemoradiation improves survival in these patients by treating micrometastases not detected by histology. Adjuvant chemoradiation should be used for patients with stage I pancreatic cancers.

Prognostic value of intraoperative blood flow measurements in vascular access surgery.

BACKGROUND: The purpose of this study was to correlate intraoperative blood flow measurements with outcome in vascular access surgery. METHODS: In 303 patients, 389 vascular access operations were performed. Intraoperative blood flow measurements were made immediately following construction of 227 autogenous and 162 prosthetic arteriovenous fistulas (AVFs) using a handheld flowprobe. Blood flow measurements were stratified by demographic variables such as age, race, sex, and presence of diabetes and were correlated with primary and secondary (assisted) patency. Statistical methods included life-table analysis and Cox proportional hazards model. RESULTS: Blood flow increased progressively from distal to proximal access sites and was not significantly affected by age, race, sex, or presence of diabetes. Autogenous AVFs with flow rates at or below 320 mL/min and polytetrafluoroethylene (PTFE) grafts with flow rates at or below 400 mL/min had significantly worse primary and secondary patency rates compared to their higher flow counterparts at all sites. Using hazard analysis flow rate was the single most important determinant of primary and secondary patency. PTFE grafts with flow rates at or below 400 mL/min also required more interventions (1.58 per patient-year) and failed sooner (median time, 0.5 +/- 4.7 months) than grafts with flow rates above 400 mL/min (1.08 interventions per patient-year; P = .03; median time, 1.6 +/- 5.0 months; P = .003). CONCLUSIONS: Intraoperative measurements of access blood flow provide objective, reliable data that correlate with outcome. Routine use of this technology might lead to more efficient management of patients undergoing hemodialysis access surgery.

Oltipraz chemoprevention trial in Qidong, People's Republic of China: modulation of serum aflatoxin albumin adduct biomarkers.

In 1995, 234 adults from Qidong, People's Republic of China, were enrolled and followed in a Phase IIa 4-methyl-5-(N-2-pyrazinyl)-1,2-dithiole-3-thione (oltipraz) chemoprevention trial. Residents of this area are at high risk for development of hepatocellular carcinoma, in part due to consumption of aflatoxin-contaminated foods. The intervention was a randomized, placebo-controlled, double-blind study. Elements of the study design and clinical outcomes have been recently published (Jacobson et al, Cancer Epidemiol. Biomark. Prev., 6: 257-265, 1997). The primary objective was to conduct a preliminary assessment of the ability of oltipraz to modulate levels of a validated biomarker of aflatoxin exposure and of the risk of hepatocellular carcinoma by determining levels of aflatoxin-albumin adducts in sera. Healthy eligible individuals were randomized into three arms to receive p.o. 125 mg of oltipraz daily, 500 mg of oltipraz weekly, or placebo for 8 weeks. There were no consistent changes in biomarker levels in the placebo arm over the 16-week observation period, nor was any apparent effect observed in the arm receiving 125 mg of oltipraz each day. However, individuals receiving 500 mg of oltipraz once a week for 8 weeks showed a triphasic response to oltipraz. No effect was observed during the 1st month of the intervention, whereas a significant (P = 0.001) diminution in adduct levels was observed during the 2nd month of active intervention and during the lst month of follow-up. A partial rebound in adduct levels toward baseline values was observed during the 2nd month postintervention. Linear regression models up to week 13 confirmed a significant (P = 0.008) weekly decline of biomarker levels in the group receiving 500 mg of oltipraz once a week. However, despite these effects relative to baseline values within the 500-mg weekly arm, there were no statistically significant differences in biomarker trajectories between treatment arms. The genotype for glutathione S-transferase M1, an oltipraz-inducible isoform involved in the detoxification of aflatoxin B1, did not appear to affect either baseline levels or rates of decline in the biomarker. A follow-up Phase IIb trial with a longer intervention period will be necessary to determine the full extent to which aflatoxin biomarker burden can be reduced and whether diminution of biomarkers can be sustained over the long term.