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Background/aims: Local ablation methods are an effective treatment for hepatocellular carcinoma (HCC). The rate of recurrence or development of intra-hepatic metastases may be lowered by antitumoral immune responses. Since HCCs are in general only weakly immunogenic, cell injury induced by local tumor ablation (PEI/RFTA) may increase HCC immunogenicity and may release endogenous adjuvants that activate dendritic cells (DC). The aim of the study, therefore, was the analysis whether PEI or RFTA induced injury results in an adjuvant effect for immune responses to HCCs., Methods: Eight HCC patients were treated with PEI or RFTA and serially analyzed for 4 weeks. Plasmocytoid (PDC) and myeloid dendritic cells (MDC) were analyzed directly ex vivo and in vitro using FACS and proliferation assays., Results: HCC ablation induced a functional transient activation of MDC but not of PDC associated with increased serum levels of TNF-alpha and IL-1beta., Conclusions: These findings suggest that the combination of PEI or RFTA and active antigen specific immunotherapeutic approaches using DCs is a promising approach for the induction of sustained antitumoral immune responses aiming at the reduction of tumor recurrence and metastases in HCC patients.

Background/aims: Novel immunotherapeutic and other strategies are being explored for the treatment of hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) may be a target antigen for immunotherapy. Little is known, however, about the immunobiology of AFP. Therefore, the impact of AFP on dendritic cells (DC), CD4+ and CD8+ T cells was studied in detail., Methods: Immune cells from peripheral blood of 27 HCC patients were studied using FACS, ELISPOT, and proliferation assays., Results: The in vitro generation, maturation, and T cell stimulatory capacity of DCs were not altered by AFP up to concentrations of 20 microg/ml. Higher AFP concentrations (> 20 microg/ml) resulted in phenotypic changes on DCs without impairing their capacity to stimulate CD4+ T cells. Frequencies and function of DCs and AFP specific T cells were not reduced in HCC patients independent on serum AFP levels. Finally, T lymphocytic infiltrations in the liver were not dependent on AFP serum levels., Conclusions: These studies clearly demonstrate that (i) DC-based immunotherapeutic approaches are a promising approach for HCC treatment and (ii) AFP-reactive T cell clones have not been deleted from the human T cell repertoire establishing AFP as a potential target for T cell based immunotherapy of HCC.

Purpose: To identify and quantify the risk of developing sarcoidosis associated with specific rural exposures previously recognized as potential risk factors for this disease., Methods: A matched case-control design was carried out with a 2-to-1 ratio of controls to cases. Case exposure histories were determine from a detailed questionnaire collecting self-reported information covering the period from birth through disease development and comparing that to exposure histories for the corresponding period in age-, race-, and gender-matched controls identified using Random Digit Dial survey methodology. Conditional logistic regression was used to analyze the matched data while controlling for several baseline variables., Results: A number of exposures were found to be univariately associated with the development of sarcoidosis including: the use of wood stoves, the use of fireplaces, the use of nonpublic water supplies, and living or working on a farm. A dose-response gradient was detected from exposure to wood stoves and fireplaces continued to be significantly associated with sarcoidosis in multivariable models., Conclusions: The results of this study provide further support for the hypothesis that behaviors associated with rural living play some role in the development of sarcoidosis. This study further suggests that exposures involving the handling or burning of wood such as using wood stoves or fireplaces for home heating may, in part, explain this rural association.

PURPOSE: The purpose of this study is to assess the patterns of geographic variation of the following pulmonary diseases: tuberculosis (TB), lung cancer (LC), berylliosis (BR), sarcoidosis (SR), and asthma (AS).METHODS: Hospitalization rates for the five diseases were calculated for the 46 South Carolina (SC) counties from 1985-1995. Variation in rates was assessed by county, region, and urban/rural status using analysis of variance. SC was divided into 4 regions, according to proximity to the coastline and to physiographic characteristics. Region 1 comprised counties in the western-most part of the state, and region 4 comprised the counties closest to the coastline. SC was also divided into 5 population density settings: extreme rural (<15,000), rural (15,000-30,000), middle-size (30,000-50,000), middle-urban (50,000-100,000) and urban (>100,000). Statistical analyses were performed with SAS Version 8.RESULTS:Table 1The rates of SR, TB, and BR were significantly higher in the coastal region. In contrast, no coastal pattern was detected by population density.CONCLUSIONS: The consistent association of SR, TB, and BR with geographical region, as opposed to the inconsistent association with population density, suggests that environmental factors may be involved in these pulmonary diseases. These results demonstrate the need for further analysis of the relationship between socio-economic, behavioral, and environmental factors and the development of these diseases.

PURPOSE: Fetal and early life events have been associated with diseases that develop later in life. Low birth weight and the adult onset of hypertension, coronary heart disease, cerebrovascular disease, and non-insulin dependent diabetes have been identified. As well, associations with breast, ovarian, and prostate cancer to high birth weight have been found. An assessment of birth weight and cancer incidence was conducted in a cohort of black and white residents under the age of 46 years.METHODS: Cases were obtained from the Savannah River Region Health Information System cancer registry incident cases (1991-1995) and were limited to South Carolinians born in 1950 and later. Controls were obtained from birth certificate records by choosing the next two records after a cancer case record that matched on year of birth, race, and sex. Results were obtained for 117 cancer cases and 238 controls.RESULTS: After examining the birth distribution, the births were split into two groups based on mean birth weight among controls (3215 grams). Conditional logistic regression (CLR) showed that individuals with higher birth weights (> = 3215 g) were 1.65 (95% CI = 1.03-2.64) times more likely to be cancer cases than those with lower birth weights. When weights were categorized into 500 g increments, a CLR Score statistic showed there was a significant trend (p = 0.0006) of increasing proportion of cancer cases with increasing birth weight. Eight out of the eight cases of lymphoma had birth weights greater than 3579 g.CONCLUSIONS: The results of this preliminary study suggest that cancer incidence among the young may be associated with higher birth weights. One possible reason for this finding, which requires further investigation, might be that larger infants are exposed to higher levels of hormones and/or growth factor than smaller infants in utero that might increase the risk of certain cancers later in life. This may be suggestive of possible environmental factors affecting early growth. These findings support the need for additional study of this association.

PURPOSE: Airline pilots are exposed to magnetic fields generated by the aircraft's electrical and electronic systems. The purpose of this study was to directly measure the flight deck magnetic fields to which commercial airline pilots are exposed when flying on different aircraft types over a 75-hour flight-duty month.METHODS: Magentic field measurements were taken using personal dosimeters capable of measuring magnetic fields in the 40-800 Hz frequency range. Dosimeters were carried by either the Captain or the First Officer on Boeing 737/200, Boeing 747/400, Boeing 767/300ER, and Airbus 320 aircraft. The data were analyzed by aircraft type, with statistics based on block hours. Block hours begin when the aircraft departs the gate prior to take off and end when the aircraft returns to the gate after landing.RESULTS: Approximately 1008 block hours were recorded at a sampling rate of 3 seconds. Total block time exposure to the pilots ranged from a harmonic geometric mean of 6.7 milliGauss (mG) for the Boeing 767/300ER to 12.7 mG for the Boeing 737/200.CONCLUSIONS: Measured flight deck magnetic field levels were substantially above the 0.8 to 1 mG level typically found in the home or office and suggest the need for further study to evaluate potential health effects of long-term exposure.

PURPOSE: High mortality rates of cervical cancer among black women have been observed for several decades in the Southeast. The purpose of this study is to assess the factors associated with this geographic and racial enigma, and to see if incidence is consistent with mortality.METHODS: Using the Savannah River Regional Health Information System (SRRHIS), a 5-year cancer registry from 1991-1995, incidence rates were calculated and compared to rates from Surveillance, Epidemiology, and End Results (SEER). The rates per 100,000/year were analyzed by race, rural/nonrural, and age (<45 and >/=45).Rates are similar between SRRHIS and SEER except in the case of black women over the age of 45. These women in rural SRRHIS have 1.66 times the incidence rate compared to those in nonrural SRRHIS and 1.97 times the rate of rural SEER.RESULTS:Table 1CONCLUSIONS: The results of the study suggest that the incidence of cervical cancer in the region is consistent with the mortality rates. The age-group with the highest rates are black women over 45 in rural areas, suggesting the need to target this group to reduce the racial disparity in cervical cancer.

We developed a specific adenoviral gene delivery system with monoclonal antibody (mAb) AF-20 that binds to a 180 kDa antigen highly expressed on human hepatocellular carcinoma (HCC) cells. A bifunctional Fab-antibody conjugate (2Hx-2-AF-20) was generated through AF-20 mAb crosslinkage to an anti-hexon antibody Fab fragment. Uptake of adenoviral particles and gene expression was examined in FOCUS HCC and NIH 3T3 cells by immunofluorescence; beta-galactosidase expression levels were determined following competitive inhibition of adenoviral CAR receptor by excess fibre knob protein. The chimeric complex was rapidly internalized at 37 degrees C, and enhanced levels of reporter gene expression was observed in AF-20 antigen positive HCC cells, but not in AF-20 antigen negative NIH 3T3 control cells. Targeting of recombinant adenoviral vectors to a tumor associated antigen by a bifunctional Fab-antibody conjugate is a promising approach to enhance specificity and efficiency of gene delivery to HCC., (Copyright 2000 Academic Press.)

One hundred nine percutaneous catheterizations of synthetic vascular grafts in 89 patients who had angiographic procedures were reviewed to determine the risk of major complications. Ninety-six of the catheterizations were inserted into the inguinal portion of aortofemoral grafts. There were no instances of hematoma, graft infection, aneurysm formation, suture line disruption, or embolic events distal to the puncture site. One local thrombus developed within a vascular graft that was corrected by a simple thrombectomy performed with a surgical catheter. One puncture site required 2 hours of compression to maintain hemostasis. Because of the extremely low risk of complications from catheterization of synthetic vascular grafts, it is the preferred route for angiographic procedures when the native femoral arterial route is unavailable.