Protein C deficiency in a controlled series of unselected outpatients: an infrequent but clear risk factor for venous thrombosis (Leiden Thrombophilia Study) [see comments]

A deficiency of protein C (PC), antithrombin, or protein S is strongly associated with deep-vein thrombosis in selected patients and their families. However, the strength of the association with venous thrombosis in the general population is unknown. This study was a population-based, patient-control study of 474 consecutive outpatients, aged less than 70 years, with a first, objectively diagnosed, episode of venous thrombosis and without an underlying malignant disease, and 474 healthy controls who matched for age and sex. Relative risks were estimated as matched odds ratios. Based on a single measurement, there were 22 (4.6%) patients with a PC deficiency (PC activity, less than 0.67 U/mL or PC antigen, less than 0.33 U/mL when using coumarins). Among the controls, the frequency was 1.5% (seven subjects). Thus, there is a threefold increase in risk of thrombosis in subjects with PC levels below 0.67 or 0.33 U/mL [matched odds ratio, 3.1; 95% confidence interval (CI), 1.4 to 7.0]. When a PC deficiency was based on two repeated measurements, the relative risk for thrombosis increased to 3.8 (95% CI, 1.3 to 10); when it was based on DNA-confirmation, the relative risk increased further to 6.5 (95% CI, 1.8 to 24). In addition, there was a gradient in thrombosis risk, according to PC levels. The results for antithrombin are similar to those for PC, although less pronounced (relative risk, 2.2; 95% CI, 1.0 to 4.7). We could not find an association between reduced total protein S (relative risk, 0.7; 95% CI, 0.3 to 1.8) or free protein S levels (relative risk, 1.6; 95% CI, 0.6 to 4.0) and thrombosis risk. Although not very frequent, PC and antithrombin deficiency are clearly associated with an increase in thrombosis risk.     

三维超声心动图测定左心耳容量及其收缩功能的初步研究

目的　观察三维超声心动图测定左心耳容量的可行性。方法　对 10名患者行多平面经食管超声心动图 (TEE)检查。应用三维超声心动图采取圆盘总和方法 (disksummation)测定左心耳舒张末期容量 (EDV)和左心耳收缩末期容量 (ESV)。用二维超声心动图测定左心耳舒张末期面积 (EDA)和左心耳收缩末期面积(ESA)。上述左心耳容量和面积的测定均在二个独立的观察者之间以及同一观察者两次观察间重复进行。由三维超声心动图容量测定结果计算出左心耳的射血分数 (EFv) ,由二维超声心动图的面积测定结果计算出左心耳射血分数 (EFa)。结果　三维超声心动图测定左心耳EDV为 ( 19.5± 10 .9)ml,ESV为 ( 13 .5± 9.5 )ml ,EFv为0 .3 5± 0 .14。二维超声心动图测定左心耳EDA为 ( 8.7± 2 .2 )cm2 ,ESV为 ( 5 .9± 3 .5 )cm2 ,EFa为 0 .3 5± 0 .2 2。以上测量内容在观察者之间及观察者内的重复性检验中均未见显著性差异 ,EFv与EFa之间亦无显著性差异。但无论在观察者间或观察者内的重复性检验中EFa的范围和两测量数值之差均大于EFv的相应值。结论　三维超声心动图测量左心耳容量和评价其收缩功能是可行的 ,这种测定方法可能有助于改善二维超声心动图评价左心耳功能的准确性。     

An update on the implications of cyclin D1 in oral carcinogenesis

Cyclin D1 promotes cell cycle progression during G1 phase, a key event in G1‐S transition. The protein is encoded by gene CCND1, located in chromosomal band 11q13. Cyclin D1 plays key roles in cell biology, including cell proliferation and growth regulation, mitochondrial activity modulation, DNA repair, and cell migration control. CCND1 gene and its protein cyclin D1 are frequently altered by different molecular mechanisms, including amplification, chromosomal translocations, mutations, and activation of the pathways involved in cyclin D1 expression, alterations which appear to be essential in the development of human cancers, including oral carcinoma. This is the first published review of the specific features of cyclin D1 overexpression in oral oncogenesis. Starting with the physiological regulation of cyclin D1, there is an evaluation of its functions, overexpression mechanisms, and the implications of the oncogenic activation of CCND1/cyclin D1 in oral squamous cell carcinoma . The potential diagnostic and prognostic value of cyclin D1 is reviewed. The influence of CCND1/cyclin D1 on tumor size and clinical stage is reported, and an update is provided on the utilization of cyclin D1 as therapeutic target and on the combination of cyclin D1 inhibitors with cytotoxic agents. Future research lines in this field are also proposed.     

100 classic papers of interventional radiology: A citation analysis

AIM: To define the 100 citation classic papers of interventional radiology.METHODS: Using the database of Journal Citation Reports the 40 highest impact factor radiology journals were chosen. From these journals the 100 most cited interventional radiology papers were chosen and analysed.RESULTS: The top paper received 2497 citations and the 100 th paper 200 citations. The average number of citations was 320. Dates of publication ranged from 1953- 2005. Most papers originated in the United States(n = 67) followed by Italy(n = 20) and France(n = 10). Harvard University(n = 18) and Osped Civile(n = 11) were the most prolific institutions. Ten journals produced all of the top 100 papers with "Radiology" and "AJR" making up the majority. SN Goldberg and T Livraghi were the most prolific authors. Nearly two thirds of the papers(n = 61) were published after 1990.CONCLUSION: This analysis identifies many of the landmark interventional radiology papers and provides a fascinating insight into the changing discourse within the field. It also identifies topics, authors and institutions which have impacted greatly on the specialty.     

Tumor-specific, cytotoxic T-lymphocyte response after idiotype vaccination for B-cell, non-Hodgkin's lymphoma

Patients with non-Hodgkin's B-cell lymphoma who received an antitumor vaccine of idiotypic ig protein showed humoral and proliferative immune responses. Because immunity to some antigens, including tumor antigens and human pathogenic viruses, may be better correlated with the cytolytic cellular immune response, we evaluated 16 non-Hodgkin's lymphoma patients immunized with autologous idiotypic ig molecules for changes in tumor-specific cytotoxic T-lymphocyte precursor (CTLp) frequency using limiting dilution analysis. Eleven patients had a significant increase in tumor-specific CTLp. Eight of these 11 patients remain without evidence of disease or with stable minimal disease. In contrast, all five patients who did not have a significant change in tumor-specific CTLp have developed progressive disease. Patient vaccination with tumor associated protein antigens can increase tumor- specific CTLp frequencies. The correlation of increased tumor specific CTLp with freedom from progression is significant at P = .002. This study indicates that measurement of CTLp frequencies are relevant to the clinical evaluation of human tumor vaccines and suggests that cell- mediated cytolytic immune responses may be an important determinant of vaccine efficacy.     

Target setting in intensive insulin management is associated with metabolic control: the Hvidoere Childhood Diabetes Study Group Centre Differences Study 2005

Swift PGF, Skinner TC, de Beaufort CE, Cameron FJ, Åman J, Aanstoot H‐J, Castaño L, Chiarelli F, Daneman D, Danne T, Dorchy H, Hoey H, Kaprio EA, Kaufman F, Kocova M, Mortensen HB, Njølstad PR, Phillip M, Robertson KJ, Schoenle EJ, Urakami T, Vanelli M, Ackermann RW, Skovlund SE for the Hvidoere Study Group on Childhood Diabetes. Target setting in intensive insulin management is associated with metabolic control: the Hvidoere Childhood Diabetes Study Group Centre Differences Study 2005. Objective: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control. Methods: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally. Results: A total of 2062 adolescents completed questionnaires (age 14.4 ± 2.3 yr; diabetes duration 6.1 ± 3.5 yr). Mean HbA 1c = 8.2 ± 1.4% with significant differences between centres (F = 12.3; p < 0.001) range from 7.4 to 9.1%. There was a significant correlation between parent (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p < 0.001), and a stronger association between parents' (r = 0.39) and adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant differences between centres on parent and adolescent reports of ideal and happy with HbA1c (8.1 < F > 17.4;p < 0.001). A lower target HbA1c and greater consistency between members of teams within centres were associated with lower centre HbA1c (F = 16.0; df = 15; p < 0.001). Conclusions: Clear and consistent setting of glycaemic targets by diabetes teams is strongly associated with HbA1c outcome in adolescents. Target setting appears to play a significant role in explaining the differences in metabolic outcomes between centres.