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PubMed1997

[The role of ionized radiation in prevention of restenosis after coronary angioplasty].

Restenosis occurs to be an Achilles heel of coronary interventions. Three overlapping processes: elastic recoil, neointimal proliferation and arterial remodelling are responsible for development of arterial renarrowing. The only method which proved efficient in reducing the restenosis rate is coronary stenting. Stents deployed using high pressure technique diminish restenosis rate by about one third. Stents eliminate elastic recoil and arterial remodelling but aggravate neointimal proliferation. A concept of radiation therapy was introduced to solve the problem of neointimal hyperplasia. Experiments on animal models of restenosis proved that both gamma as well as beta irradiation inhibited neointimal proliferation after arterial injury. Results of experimental investigations concerning both intraarterial irradiation during angioplasty as well as radioactive stent implantation are reviewed. Authors discuss also results of first clinical trials, the design and preliminary results of some larger studies like PARIS, SCRIPPS, GENEVA, BERT, IRIS, WRIST. Further investigational directions in intravascular radiation therapy are also presented.

Angioplasty, Balloon, Coronary↗
PubMed2003

Isolated postaxial polydactyly type B with mosaicism of a submicroscopic unbalanced translocation leading to an extended phenotype in offspring.

Postaxial polydactyly (PAP) is characterized by the presence of one or more extra ulnar or fibular digits or parts of it. PAP type B presents frequently as a skin tag on the hand(s). It is usually an isolated malformation, but in 6.6% it is associated with other congenital abnormalities, mostly well recognizable syndromes. We present a male with PAP-B only and his daughter with an extended phenotype including mental retardation and minor dysmorphisms. Both share a cytogenetically balanced t(4;7)(p15.2;q35), present in mosaicism in the father. We found microdeletions associated with the breakpoints. The chromosomal regions described here have not been previously associated with the PAP-B phenotype. We present the first case of an individual with isolated PAP-B and a submicroscopic chromosome abnormality.

Abnormalities, Multiple↗
PubMed2006

Treatment decision making in prostate cancer: patients' participation in complex decisions.

OBJECTIVE: (1) To explore to what degree prostate cancer (PC) patients felt they had participated in treatment decision making (TDM). (2) To determine whether perceived roles during TDM were associated with medical and sociodemographic variables. (3) To examine to what extent satisfaction with TDM was related to perceived role or medical and sociodemographic variables. METHODS: Patients (n=126) were recruited in hospitals and from the Dutch PC patient organization. The relationship between patients' role and stage of disease, treatment modality, age, social status and education was determined, as well as patients' satisfaction with TDM. RESULTS: Most patients felt they had participated in TDM (autonomous 18%, collaborative 60%). Older patients and those with advanced disease more frequently reported not having been involved in decision making. Satisfaction with TDM was related to age and role in TDM but not to stage of disease or treatment modality. Younger men were least content when they had not been involved in decision making. CONCLUSION: Patients' level of participation and satisfaction with TDM appears to be related to medical and sociodemographic variables. PRACTICE IMPLICATIONS: Satisfaction with TDM may be related to patients' age and assumed role. It is recommended to take this into account when planning treatment for prostate cancer patients.

Aged↗
PubMed2005

The impact on rural New Mexico of a family medicine residency.

PURPOSE: To determine the impact on rural New Mexico of the large, decentralized University of New Mexico (UNM) family medicine residency. METHOD: A cross-sectional study was conducted of all 317 residency's graduates from 1974 to 2004. Location of current practice was correlated with the residents' gender, ethnicity, medical school of origin, and whether most training took place in the urban program or one of three rural programs. The residency's impact on rural communities was assessed. RESULTS: There was no significant gender difference between graduates who went into urban or rural practice. Compared with non-minority graduates, a significantly greater percentage of ethnic minority graduates were in rural and urban New Mexico practices and fewer in out-of-state practices. A greater percentage of graduates who had been medical students in New Mexico practiced in both rural and urban New Mexico areas compared with graduates of out of state medical schools. Finally, a greater percentage of graduates from the three rural family medicine residencies remained in the state and practiced in rural areas compared with graduates from the urban program. The graduates' contributions to the school of medicine and to rural New Mexico are described. CONCLUSIONS: Graduates of UNM's family medicine residency have contributed significantly to the state's rural health workforce. Ethnic minority status, graduation from New Mexico's medical school, and training in one of the three rurally based residencies favored in-state and rural retention, while gender had no significant effect. The rural orientation of the residencies offered rural communities economic benefits.

Career Choice↗
PubMed2006

Health-related quality of life in Dutch men with prostate cancer.

Prostate cancer is the most prevalent solid malignancy in men in the Netherlands. With regard to treatment, the focus of attention has shifted in the last decade from pure survival rates to health-related quality of life. HRQOL is affected differently by different treatments. The objective of this study is to assess the HRQOL related to treatment regime and time since diagnosis in Dutch men with prostate cancer. We conducted a cross-sectional study among 238 men with prostate cancer in a heterogeneous sample who filled in a general health-related quality-of-life measure (EORTC-QLQ-C30) and a prostate cancer specific quality-of-life instrument (the EORTC-QLQ-PR25) and a Joy-of-Life questionnaire. Men on hormonal treatment are doing worse compared with other treatments with respect to physical functioning, role functioning, fatigue, pain and sexual functioning. No differences were found between radical prostatectomy and radiation therapy on any of the HRQOL dimensions nor for time since diagnosis. In hormonal therapy, men who are diagnosed longer than two years ago report a worse cognitive functioning and more burdens from urinary problems.

Adult↗
PubMed2002

Simplification of the diagnostic management of suspected deep vein thrombosis.

BACKGROUND: The standard diagnostic approach in patients with suspected deep vein thrombosis is to repeat the compression ultrasonography after 1 week in all patients with an initial normal result. We hypothesized that a normal finding of a D-dimer assay safely obviates the need for repeated ultrasonography. In addition, we evaluated the potential value of a pretest probability assessment for this purpose. METHODS: At presentation, consecutive outpatients with suspected thrombosis underwent independent assessment by means of ultrasonography of the proximal veins, a whole-blood D-dimer assay, and a pretest clinical model. Patients with normal ultrasonographic findings and an abnormal D-dimer assay result were scheduled for repeated ultrasonography. We evaluated the incidence of symptomatic venous thromboembolic complications during a 3-month follow-up, and the value of clinical pretest probability with ultrasonography or D-dimer assay in scenario analyses. RESULTS: We studied 1756 patients with prevalence of thrombosis of 22%. At entry, results of the D-dimer assay and ultrasonography were normal in 828 patients (47%). Of these, 6 returned with confirmed symptomatic venous thromboembolism (complication rate, 0.7%; 95% confidence interval [CI], 0.3%-1.6%). Repeated ultrasonography was avoided in 61% of the patients with an initial normal test result. Scenario analyses disclosed that the complication rate was 1.6% (95% CI, 0.8%-2.6%) in those with a low clinical pretest probability and a normal result of ultrasonography at referral, whereas this figure was 1.8% (95% CI, 0.9%-3.3%) in patients with a low clinical probability result and a normal result of the D-dimer assay at referral. CONCLUSIONS: It is safe to withhold repeated ultrasonography in patients with suspected deep vein thrombosis who have normal results of ultrasonograpy and the SimpliRED D-dimer assay at presentation. The combination of a low clinical pretest probability with a normal result of compression ultrasonography or the D-dimer assay appears to be equally safe in refuting the diagnosis of deep vein thrombosis.

Adolescent↗
PubMed2003

Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial.

BACKGROUND: Tea consumption has been associated with decreased cardiovascular risk, but potential mechanisms of benefit are ill-defined. While epidemiologic studies suggest that drinking multiple cups of tea per day lowers low-density lipoprotein cholesterol (LDL-C), previous trials of tea drinking and administration of green tea extract have failed to show any impact on lipids and lipoproteins in humans. Our objective was to study the impact of a theaflavin-enriched green tea extract on the lipids and lipoproteins of subjects with mild to moderate hypercholesterolemia. METHODS: Double-blind, randomized, placebo-controlled, parallel-group trial set in outpatient clinics in 6 urban hospitals in China. A total of 240 men and women 18 years or older on a low-fat diet with mild to moderate hypercholesterolemia were randomly assigned to receive a daily capsule containing theaflavin-enriched green tea extract (375 mg) or placebo for 12 weeks. Main outcome measures were mean percentage changes in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglyceride levels compared with baseline. RESULTS: After 12 weeks, the mean +/- SEM changes from baseline in total cholesterol, LDL-C, HDL-C, and triglyceride levels were -11.3% +/- 0.9% (P =.01), -16.4% +/- 1.1% (P =.01), 2.3% +/- 2.1% (P =.27), and 2.6% +/- 3.5% (P =.47), respectively, in the tea extract group. The mean levels of total cholesterol, LDL-C, HDL-C, and triglycerides did not change significantly in the placebo group. No significant adverse events were observed. CONCLUSION: The theaflavin-enriched green tea extract we studied is an effective adjunct to a low-saturated-fat diet to reduce LDL-C in hypercholesterolemic adults and is well tolerated.

Adult↗
PubMed2005

The ethics of research using biobanks: reason to question the importance attributed to informed consent.

BACKGROUND: During the past decade, the use of stored tissue has become an object of increased ethical query. A Swedish biobank and a biotech company have been praised for solving the ethical problems with explicit informed consent procedures, and we decided to investigate donors' perceptions of the system. METHODS: A questionnaire was sent to a randomized sample of 1200 donors who had donated blood and signed informed consent forms. RESULTS: The response rate was 80.9%. Of the respondents, 64.5% were aware that they had consented to donate a blood sample, 55.4% thought that they had consented to donate phenotypic information, and 31.6% believed that they could withdraw their consent. Among respondents, 3.9% considered informing donors about the research objective as the most important ethical issue in relation to biobanks, and 5.6% were unsatisfied with the information they had been given. There was 85.9% acceptance of surrogate decision making by regional research ethics committees. CONCLUSIONS: Considering that the donors in this study were not always aware of their donation but generally were not unsatisfied with the information they had received, and that they did not rate being informed about the research objective as an important issue, informed consent seems to be an inadequate measure of public acceptance of biobank-based research.

Biotechnology↗
PubMed2003

Combination nonviral interleukin 2 gene therapy and external-beam radiation therapy for head and neck cancer.

OBJECTIVES: To demonstrate that the combination of nonviral murine interleukin 2 (mIL-2) gene therapy and external-beam radiation therapy (XRT) have an enhanced therapeutic effect for the treatment of head and neck squamous cell carcinoma (HNSCC) in an orthotopic murine model and to elucidate the mechanism of action. METHODS: Randomized, controlled studies in the murine orthotopic model of HNSCC. Squamous cell carcinoma VII cells were injected into the floor of the mouth to establish tumors in immunocompetent mice. The intervention groups were treated with mIL-2, radiation therapy, empty plasmid, no treatment, combination mIL-2/XRT, and combination empty plasmid/XRT. Nonviral mIL-2 gene transfer was performed on days 5 and 9. The XRT was administered to the assigned groups 24 hours after first mIL-2 delivery. The mice were killed on day 13. Tumors and local lymph nodes were harvested and evaluated. Primary and secondary cytokine expression, cytotoxic T-lymphocyte activity, and apoptosis were assayed. RESULTS: The combination mIL-2/XRT demonstrated a significant increase in antitumor effects compared with single therapy or controls. Increased expression levels of primary and secondary cytokines were found in the group treated with mIL-2, and this effect was preserved when mIL-2 treatment was combined with XRT. Combination therapy significantly increased apoptosis compared with monotherapy. CONCLUSIONS: The present study demonstrates that combination mIL-2/XRT generates potent antitumor immune responses and significantly increases apoptosis in an orthotopic murine model of HNSCC. Further optimization of this strategy is warranted as well as consideration for human clinical trials.

Animals↗
PubMed2006

Microvascular reconstruction of cranial base defects: An evaluation of complication and survival rates to justify the use of this repair.

OBJECTIVES: To describe our experience, including selection criteria and complication rates, using microvascular free tissue transfer to repair large skull base defects and to determine if complication rate and posttreatment survival justify the use of this technique. DESIGN: Retrospective review of clinical cohort. SETTING: Tertiary care medical center. PATIENTS: A consecutive sample of patients undergoing ablative surgery with repair of cranial base defects with free tissue transfer from 1995 to 2004. All the patients' defects involved intracranial exposure. MAIN OUTCOME MEASURES: Rate of local and systemic complications, postoperative survival, and recurrence rate. RESULTS: The study population comprised 40 patients. Fifteen (38%) of the patients' defects were in the anterior cranial base, and 26 (65%) were in the middle cranial base. We used 5 types of free tissue flap, with a success rate of 95%. Our rate of perioperative mortality, meningitis, stroke, cerebrospinal fluid leak, epidural abscess, and osteomyelitis was 0%. We had 7 local complications and 4 systemic complications requiring increased length of hospital stay. Including microvascular problems, 12 patients had complications, for an overall complication rate of 30%. Follow-up ranged from 1 to 96 months, with a mean of 24 months. The tumor recurrence rate was 30%, and disease-specific survival was 81% at a mean 24-month follow-up. CONCLUSIONS: We did not experience any perioperative mortality or intracranial morbidity. Our low complication rate in combination with our tumor recurrence rate and rate of patient survival justify the use of free tissue transfer as an option in the closure of appropriate cranial base defects.

Adolescent↗
PubMed2004

Isolated limb perfusion for unresectable melanoma of the extremities.

HYPOTHESIS: In patients with truly unresectable melanoma of the extremities, results after isolated limb perfusion (ILP) are absent in the literature. Complete response rates are probably lower than the reported 54% for locoregional recurrent melanoma. In these patients, ILP with melphalan and tumor necrosis factor alpha (TNF-alpha) could be superior to ILP with melphalan alone. DESIGN: Retrospective analysis with a median follow-up period of 21 months (interquartile range, 9-40 months). SETTING: Two tertiary care cancer centers in the Netherlands. PATIENTS: We assessed all 130 consecutive patients who underwent ILP for unresectable melanoma of the extremities, performed between 1978 and 2001. Of these patients, 38% had stage IIIA melanoma and 45% had stage IIIAB melanoma according to criteria of the MD Anderson Cancer Center. Lesions were considered unresectable on the basis of their size, number, or localization. INTERVENTIONS: Forty ILPs were performed with melphalan, and 90 were done with TNF-alpha and melphalan. MAIN OUTCOME MEASURES: Response rate, disease-free survival, limb salvage rate, and overall survival. RESULTS: In 45% of the patients, a complete response was attained after ILP with melphalan (95% confidence interval, 29%-61%) compared with 59% after ILP with TNF-alpha and melphalan (95% confidence interval, 49%-69%; P = .14). The time to complete response was 3 months (interquartile range, 2-6 months) vs 2 months (interquartile range, 1-3 months; P = .01), respectively. The recurrence rate and median limb recurrence-free survival were not significantly different for both ILP types. The overall limb salvage rate was 96%. Overall 5-year survival was 29% (95% confidence interval, 20%-38%). The ILP type was not an independent prognostic factor for complete response, nor was limb recurrence-free survival, whereas stage IIIA was a favorable prognostic factor (P = .01 and P = .02, respectively). Favorable prognostic factors for improved survival were complete response (P<.001) and a tumor size of 3 cm or less (P = .01). CONCLUSIONS: In more than half of the patients with truly unresectable melanoma of the extremities, a complete response was obtained after ILP with melphalan with or without TNF-alpha. The ILP type was not an independent prognostic factor for complete response, limb recurrence-free survival, or overall survival.

Adult↗
PubMed1999

Occupational risk factors for prostate cancer mortality in British Columbia, Canada.

BACKGROUND: Although prostate cancer is the most common life-threatening cancer among males in North America, relatively little is known about its etiology. We have conducted a proportional mortality study to generate hypotheses concerning occupational risk factors for the disease. METHODS: Age standardized proportional mortality ratios (PMR) for prostate cancer were calculated for a total of 216 occupations and 88 industries. Separate calculations were done for all male deaths age 20 and up and for deaths that occurred during men's working lifetime (age 20-65). RESULTS: Elevated mortality from prostate cancer was seen among business owners and managers (PMR = 110; 95% CI = 101-118), brokers (PMR = 184; 95% CI = 122-266), farmers and farm managers (PMR = 112; 95% CI = 105-120), and school teachers (PMR = 133; 95% CI = 101-174). Evaluation by industry shows elevated prostate cancer mortality in agriculture (PMR = 110; 95% CI = 103-118), financial institutions (PMR = 138, 95% CI = 112-170), and transportation equipment manufacture (PMR = 136; 95% CI = 109-168). CONCLUSIONS: The findings suggest that workers in a number of occupations have elevated risks of prostate cancer including farmers and teachers. More detailed cohort and case-control studies, evaluating specific exposures are required before primary prevention programs in the workplace are feasible.

Adult↗
PubMed2000

Cervical spondylosis: contrast-enhanced magnetization transfer prepulsed 3D turbo field echo MR imaging.

Magnetic resonance (MR) imaging of the cervical spine with axial, low flip angle three-dimensional (3D) gradient-echo sequences is limited by long acquisition times and also by increased sensitivity to extrinsic and intrinsic magnetic field inhomogeneity, magnetic susceptibility differences, chemical shifts, and cerebrospinal fluid pulsatility. We attempted to assess the performance of gadolinium-enhanced, magnetization transfer (MT) prepulsed 3D fast gradient-echo sequences in demonstrating spondylotic changes of the cervical spine. Twenty patients with known cervical spine spondylosis were prospectively imaged in the axial plane using two gradient-echo-based MR techniques: 3D fast field echo (FFE) and gadolinium-enhanced, MT prepulsed, segmented turbo field echo (TFE). An average of 58 neural foramina on the 3D FFE images and 47 neural foramina on the contrast-enhanced TFE images were judged to be narrowed. The degree of neural foraminal narrowing was significantly less on the contrast-enhanced TFE images compared with the FFE images (P <0.001). Contrast-enhanced, MT prepulsed, segmented 3D TFE MR imaging has potential for ameliorating some of the limitations encountered in the more widely used gradient-echo techniques.

Cervical Vertebrae↗
PubMed2002

Optical and redox properties of a series of 3,4-ethylenedioxythiophene oligomers.

The optical and redox properties of a series of 3,4-ethylenedioxythiophene oligomers (EDOTn, n=1-4) and their beta,beta'-unsubstituted analogues (Tn, n=1-4) are described. Both series are end capped with phenyl groups to prevent irreversible alpha-coupling reactions during oxidative doping. Absorption and fluorescence spectra of both series reveal a significantly higher degree of intrachain conformational order in the EDOTn oligomers. Oxidation potentials (E(PA1) and E(PA2)) determined by cyclic voltammetry reveal that those of EDOTn are significantly lower than the corresponding Tn oligomers as a consequence of the electron-donating 3,4-ethylenedioxy substitution. Linear fits of E(PA1) and E(PA2) versus the reciprocal number of double bonds reveal significantly steeper slopes for the EDOTn than for the Tn oligomers. This could indicate a more effective conjugation for the EDOTn series, confirmed by the fact that coalescence of E(PA1) and E(PA2) is reached already at relatively short chain lengths ( approximately 5 EDOT units) in contrast to the Tn series (>10 thiophene units). The stepwise chemical oxidation of the EDOTn and Tn oligomers in solution was carried out to obtain radical cations and dications. The energies of the optical transitions of the radical cations and dications as determined by UV/Vis/NIR spectroscopy were similar for the two series. These spectroscopic observations are consistent with quantum-chemical calculations performed on the singly charged molecules. Cooling solutions containing T2.+, T3.+, EDOT2.+, and EDOT3.+ revealed the reversible formation of dimers, albeit with a somewhat different tendency, expressed in the values for the dimerization enthalpy.

Journal Article↗