Occupational magnetic field exposure, cardiovascular disease mortality, and potential confounding by smoking

PURPOSE: To assess the relationship between occupational magnetic field (MF) exposure and cardiovascular disease (CVD) mortality and to determine whether smoking could confound this relationship. METHODS: Death certificate and proxy respondent information from the US 1986 and 1993 National Mortality Followback Surveys (NMFS) were used to determine whether job titles with potential occupational MF exposure were risk factors for CVD mortality and whether smoking behavior may confound the observed relationship. A qualitative MF exposure matrix was developed based on job titles and published exposure measurements. In a case-control analysis, logistic regression models, adjusting for age, sex, race, working status, level of education, and survey year, were used to examine the associations between estimated MF exposure and death from CVD. To assess the effect of adjustment for smoking, we conducted our analyses with and without including smoking-related variables in the models, and evaluated the change in CVD risk estimates. RESULTS: There was no consistent dose-response relationship between occupational MF exposure estimates and CVD mortality. Adjustment for smoking behavior did not appreciably change the observed MF exposure-CVD mortality relationship. CONCLUSIONS: Although limited by self-reported information on exposure and smoking, our results suggest that CVD mortality was not associated with MF exposure in this study, and smoking behavior was not an apparent confounder of the MF-CVD association.     

Inpatient admissions for interventional radiology: philosophy of patient management

As an alternative to performing interventional radiology on inpatients under the care of internists and surgeons, the authors have established a cardiovascular radiology admitting service for well-screened, elective patients. The patients are admitted under the care of a cardiovascular radiology fellow and a staff physician. From April 1982 to December 1983, 133 patients were admitted to the service. Patients are cared for in a surgical ward or in an intermediate unit, as determined by the clinical situation. Advantages of this approach include a broader patient referral base, improved rapport with clinical colleagues and patients, improved follow-up data, and rapid evaluation and treatment, resulting in short hospital stays. The major disadvantages involve the commitment of time and staff necessary to provide quality care. The concept of the interventional radiologist in the role of admitting physician has important implications in terms of negotiations for additional financial compensation, commensurate with the skill and time required for performing these procedures and caring for the patient.     

Differential regulation of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 expression in co-cultures of prostate cancer and stromal cells

Tumor-stromal interactions have been suggested to be a critical factor in both tumor invasion and tumor metastasis. Here, we examined the role of tumor-stromal interactions using co-cultures of prostate cancer (PC) cells derived from primary and metastatic tumors with primary or immortalized stromal (fibroblast and smooth muscle) cells and their effect on matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) expression. Co-cultures of PC and stromal cells showed enhanced levels of pro-MMP-9 and reduced levels of TIMP-1 and TIMP-2. Whereas enhanced expression of pro-MMP-9 occurred in PC cells, the TIMPs were down-regulated in stromal cells. Induction of pro-MMP-9 and reduction of TIMP expression did not require cell-cell contact and were mediated by a soluble factor(s) present in the conditioned medium of the effector cell. Collagen I is a potent inducer of pro-MMP-9 in PC cells. Consistently, preliminary characterization of the soluble factor in the fibroblast conditioned medium revealed m.w. of approximately 100 to 250 kDa, and its effect on pro-MMP-9 expression was partly inhibited by an anti-alpha2 integrin antibody, a major collagen I receptor. Expression of pro-MMP-9 protein and mRNA was also induced in metastatic PC-3 cells grown in human fetal bone implants in SCID mice. Together, these findings demonstrate the importance of tumor-stromal interactions in the regulation of MMP and TIMP expression and their potential role in PC progression.     

Stepwise genetic changes associated with progression of nontumorigenic HPV-18 immortalized human prostate cancer-derived cell line to a malignant phenotype

Cytogenetics, fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH) were used to identify genes that are involved in the development and progression of prostate cancer. For that purpose, we chose a cell line established in vitro from a prostatic adenocarcinoma which was nontumorigenic in nude mice and followed its progression to a tumorigenic cell line. Stepwise changes were observed in the cell line as it became tumorigenic. The composite karyotype at the nontumorigenic stage (CA-HPV-10) was 68 approximately 77,XXY,-(1, 9, 13, 14, 19, 22),+(4, 5, 11, 18, 20, 21),+(del(1) (q23q31)=M1 (two copies), +der(9)t(1;9)(q24 approximately q31;p23)=M5(two copies), der(14)t(14;?)(q10;?)=M17 in the majority of metaphases. These two derivative chromosomes were also observed a previous study. Our CGH analysis clearly showed that this deleted region in M1 is, in fact, translocated with derivative M5 and, in reality, is amplified. The cell line established from nodule (SCID 5019 p11), showed a number of new changes, as described; however, the most significant change was amplification of the 8q23 approximately qter region, harboring c-myc. This region was translocated with chromosomes 2, 4, and 16 as der(2)t(2;8)(q33;q23)=M12, der(4)t(4;8)(q34;q23)=M11, and der(16)t(8;16)(q24;q21)=M9. We deduce from our study that amplification of c-myc and other genes in the 8q23 approximately qter region were important in progression but did not lead to tumorigenicity. The population that became tumorigenic (SCID 5019 II) showed almost all of the same changes in the karyotype as observed in the nodular cell line; the only significant change was the appearance of der(11)t(4;11)(q32;q22)=M7 and the addition of another copy of t(3q;7p)=M2. These new changes lead to loss of chromosomes 3p, 4pter approximately q34, 6, 7q21 approximately qter, 11q22 approximately qter, and 18q, and gain of 3q, 7p, 8q23 approximately qter, and 11pter approximately q22, before the cell line became tumorigenic. The clonal selection of the population is proven by the presence of a number of the same derivative chromosomes in both the nodular and tumorigenic cell line. As it progressed to tumorigenicity, some of the same changes observed in the original study re-appear at different stages of malignancy, although it was absent in the nontumorigenic cell line. These are: der(16)t(8;16)(q24;q21)=M9 in the nodular cell line and der(11)t(4;11)(q32;q22)=M7 in the tumorigenic cell line. In our system, amplification of c-myc and other genes in der(2)t(2;8)(q33;q23)=M12,der(4) t(4;8)(q34;q23)=M11 together with the presence of der(16)t(8;16)(q24;q21)=M9 and der(11)t(4;11)(q32;q22)=M5 makes the cell line tumorigenic. It is either nontumorigenic, with the presence of a marker equivalent to der(16)=M9 and der(11)=M7 observed in the original study, and only nodular (SCID 5019 p11, present study), with the presence of number of markers with c-myc amplification (M9, M11, and M12). There is accumulation of all the above-mentioned changes in the same cell before it becomes tumorigenic.     

Prospects of immunotherapy for the treatment of prostate carcinoma--a review.

The treatment of prostate carcinoma is dependent on the stage of the disease. Patients who present with clinically localized cancer or locally advanced tumors can be potentially cured by radical prostatectomy, radiation, and hormonal therapy. However, disease progression can occur in 30-50% of patients diagnosed with clinically localized cancer. The bone is the predominant site of metastases. Metastatic prostate cancer is first treated by androgen blockade but within a few months becomes hormone refractory. Hormone refractory metastatic prostate cancer is not responsive to conventional treatments, and patients have an expected survival of less than a year. It is essential to develop new approaches for the treatment of hormone refractory metastatic disease. Immunotherapy, based on enhancement of the host immune response against the tumor, has been used as an alternative therapy for the treatment of metastatic cancers refractory to conventional therapy in particular for melanoma and renal cell carcinoma. In this review, we will summarize various immunotherapeutic approaches developed over the last 18 years, and we will address the potential of immunotherapy for the treatment of metastatic prostate carcinoma by reviewing preclinical studies and initial clinical trials performed in this field.     

基因芯片技术在脑损伤研究中的应用

基因芯片技术是最近发展起来的新兴分子生物学技术,它的并行处理特点使大规模研究脑损伤后的基因改变成为切实可能。本文综述了新近用基因芯片技术在脑损伤后基因表达时序性改变及基因表达谱分析等研究中的应用。     

Results of randomized controlled trials of low-versus high-osmolality contrast media

The authors reviewed 100 randomized controlled trials (RCTs) conducted in humans to compare safety or efficacy of new low-osmolality contrast media (LOM) with that of high-osmolality contrast media (HOM). Findings of the 43 RCTs judged to be of the highest quality suggest that the efficacy of LOM in imaging is equal or superior to that of HOM for all routes of administration. Heat sensation occurred less often with LOM for all routes and pain occurred less often with LOM for intraarterial routes. No differences were seen in nephrotoxicity or in frequency of nausea, vomiting, urticaria, bronchospasm, laboratory test abnormalities, or neurologic events. Greater cardiovascular changes were seen with HOM, including increased or decreased heart rate, increased left ventricular end-diastolic pressure, decreased systolic pressure, and QT prolongation, depending on route of administration. To demonstrate whether a reduction in clinically significant adverse outcomes truly occurs with LOM, trials will need to enlist larger numbers of patients and employ appropriate outcome measures. Future trials should stratify patients according to their risk of adverse reactions to provide better information about benefits of LOM in low- versus high-risk patients.     

Isthmic spondylolysis of the lumbar spine: MR imaging at 1.5 T

The appearance on magnetic resonance (MR) images of the normal pars interarticularis in 13 patients was reviewed and contrasted with that of the pars in eight patients with spondylolysis. The pars defect usually had an intermediate signal intensity with all pulse sequences; however, this intensity was somewhat variable depending on the exact ratio of cartilage, fat, and fluid within each bone defect. The pars defect was best seen with spin-echo 600/20 (repetition time msec/echo time msec) images. In three cases, out-of-phase images showed the spondylolysis best, because of extension of fat to the borders of the defect. The sagittal view allowed one to separate spondylolysis from the joint space of posterior facets since the orientation of the defects is perpendicular to the facets; thus, a common pitfall encountered with cross-sectional axial imaging techniques is avoided. MR imaging poorly delineated bone fragments around the defect, which may produce nerve root impingement, but revealed other numerous complications that occur with spondylolysis, including spondylolisthesis and herniation of the disk above.     

Transabdominal versus endovaginal pelvic sonography: prospective study

Transabdominal and endovaginal pelvic sonograms were obtained in 108 nonpregnant patients referred for pelvic sonography. The studies were independently obtained by two radiologists and interpreted on the basis of identical clinical information. The sonograms were then compared for anatomic detail and abnormalities. A determination was made about which examination, if either, was superior. Follow-up was performed through a review of the medical records and follow-up studies. Overall, the endovaginal study was judged superior in 65 cases (60.2%), equal in 39 (36.1%), and inferior in four (3.7%). The authors conclude that the endovaginal examination can effectively replace the transabdominal examination as the initial approach for routine pelvic sonography.