Systematic Review and Meta-analysis of Circulatory Disease from Exposure to Low-Level Ionizing Radiation and Estimates of Potential Population Mortality Risks

Background: Although high doses of ionizing radiation have long been linked to circulatory disease, evidence for an association at lower exposures remains controversial. However, recent analyses suggest excess relative risks at occupational exposure levels.Objectives: We performed a systematic review and meta-analysis to summarize information on circulatory disease risks associated with moderate- and low-level whole-body ionizing radiation exposures.Methods: We conducted PubMed/ISI Thomson searches of peer-reviewed papers published since 1990 using the terms “radiation” AND “heart” AND “disease,” OR “radiation” AND “stroke,” OR “radiation” AND “circulatory” AND “disease.” Radiation exposures had to be whole-body, with a cumulative mean dose of < 0.5 Sv, or at a low dose rate (< 10 mSv/day). We estimated population risks of circulatory disease from low-level radiation exposure using excess relative risk estimates from this meta-analysis and current mortality rates for nine major developed countries.Results: Estimated excess population risks for all circulatory diseases combined ranged from 2.5%/Sv [95% confidence interval (CI): 0.8, 4.2] for France to 8.5%/Sv (95% CI: 4.0, 13.0) for Russia.Conclusions: Our review supports an association between circulatory disease mortality and low and moderate doses of ionizing radiation. Our analysis was limited by heterogeneity among studies (particularly for noncardiac end points), the possibility of uncontrolled confounding in some occupational groups by lifestyle factors, and higher dose groups (> 0.5 Sv) generally driving the observed trends. If confirmed, our findings suggest that overall radiation-related mortality is about twice that currently estimated based on estimates for cancer end points alone (which range from 4.2% to 5.6%/Sv for these populations).     

rCBF abnormalities detected,and sequentially followed,by SPECT in neuro-Behcet's syndrome with normal CT and MRI imaging

Summary Conventional imaging with computed tomography (CT) and magnetic resonance imaging (MRI) may show abnormalities in central nervous system Behcet's syndrome but is normal in some cases. Recently in two cases positron emission tomography has shown abnormalities in blood flow and glucose metabolism far more extensive than the abnormalities seen on CT and MRI scans in the same patients. We report a patient with neuro-Behcet's syndrome presenting with headache and personality change in whom CT and MRI brain imaging was normal, but regional cerebral blood flow imaging using single photon emission tomography with the tracer HMPAO showed extensive perfusion deficits which partially reversed after 3 months of prednisolone therapy. This technique may aid the diagnosis of cerebral involvement in Behcet's syndrome, although the cause and incidence of the perfusion deficits need further evaluation.     

Proteinase-activated receptor-1 (PAR-1) activation contracts the isolated human renal artery in vitro

1. The in vitro motor function of protease-activated recepter-1 (PAR-1), PAR-2 and PAR-4 and the presence by immunohistochemistry of PAR-1 in the human renal artery have been investigated. 2. Thrombin and the human PAR-1 (SFLLRN-NH(2)) activating peptide, but not the PAR-1 reverse peptide (NRLLFS-NH(2)), contracted both endothelial-intact and endothelial-denuded human renal artery strips, whereas no relaxation was observed either in strips non-precontracted or precontracted with phenylephrine. Maximum contraction by thrombin or SFLLRN-NH(2) was about 60% of phenylephrine. However, thrombin was approximately 1000-fold more potent than SFLLRN-NH(2). 3. PAR-1 desensitisation, using repeated applications of SFLLRN-NH(2), almost completely blocked the response to thrombin. The contractile effect produced by thrombin and SFLLRN-NH(2) was not affected by nitric oxide synthase inhibition, but was significantly reduced by cyclooxygenase blockade. 4. Trypsin, the PAR-2 (SLIGKV-NH(2) and SLIGRL-NH(2)) and PAR-4 (GYPGQV-NH(2) and AYPGKF-NH(2)) activating peptides did not produce any significant contraction or relaxation. 5. In agreement with the motor function data immunohistochemistry showed specific staining patterns for PAR-1 in the human renal artery. 6. Combined, these studies would suggest a possible role for PAR-1 in renal vascular homeostasis.     

METHYLATION STATUS OF BCL6 DISTINGUISHES DNA SAMPLES FROM BENIGN AND MALIGNANT LYMPHOPROLIFERATIVE DISORDERS

INTRODUCTION: Core biopsy of the breast has become the method of choice for tissue diagnosis of screen detected microcalcifications and some mass lesions in many breast assessment centres. Biopsy results are not available until the following day. Imprint cytology of fresh breast core samples allows same-day reporting and patient counselling.
AIM: To determine the accuracy of core imprint cytology when compared with core biopsy diagnosis when used in a breast assessment centre setting.
METHODS: Core imprints (CI) were prepared and reported on all fresh core biopsies (CB) performed at the Sir Charles Gairdner Hospital Breast Centre from May to December 2000. Fresh core samples were placed on a glass microscope slide. Core radiographs were taken for microcalcification lesions (MC). A laboratory technician gently and quickly rolled the cores on the slide with fine forceps. The cores were fixed in formalin, processed and reported next day. The imprint slide was air dried and stained with DiffQuik. CI were reported using four categories: Insufficient, Benign, Indeterminate and Malignant. Counselling and planning for management were possible on the same day in women with malignant diagnoses. Clinicians were advised not to discuss negative or indeterminate CI results with women and to defer to the final CB report.
RESULTS: Cores were performed on 381 lesions. There were 83 carcinomas (38 in MC and 45 in masses) and 56 were called malignant on CI (absolute sensitivity 67.5%; 78.9% for MC and 57.8% for masses). 3 malignancies on CB were negative on CI giving a false negative rate of 3.6%. There were no false positive diagnoses. The predictive value of a benign diagnosis was 95.3%. There were no adverse effects in the histology of CB.
CONCLUSION: CI was an accurate method of providing an immediate diagnosis of malignancy in two thirds of malignancies confirmed on CB.     

Toxicity of glutaminase in patients with advanced lymphoblastic leukaemia

Fifteen patients with relapsed lymphoblastic leukaemia were treated with a glutaminase isolated from Achromobacter sp. using this enzyme for the first time in combination with other drugs in the treatment of human leukaemia.Although two patients achieved complete remission, and a further three partial remission, five patients showed acute hypersensitivity to the glutaminase and two of the five required resuscitation. Also one patient developed hyperglycaemic ketoacidosis 36 h after receiving the enzyme for the first time, and three others had biochemical evidence of carbohydrate intolerance. All patients experienced nausea and vomiting shortly after the start of the first infusion which lessened with second and third courses, and did not necessitate withdrawal of the drug.The high incidence of side effects in these patients indicates that despite the anti-leukaemic activity of this enzyme its application is limited by poor patient acceptability.     

Highly accelerated real‐time cardiac cine MRI using k–t SPARSE‐SENSE

For patients with impaired breath‐hold capacity and/or arrhythmias, real‐time cine MRI may be more clinically useful than breath‐hold cine MRI. However, commercially available real‐time cine MRI methods using parallel imaging typically yield relatively poor spatio‐temporal resolution due to their low image acquisition speed. We sought to achieve relatively high spatial resolution (～2.5 × 2.5 mm²) and temporal resolution (～40 ms), to produce high‐quality real‐time cine MR images that could be applied clinically for wall motion assessment and measurement of left ventricular function. In this work, we present an eightfold accelerated real‐time cardiac cine MRI pulse sequence using a combination of compressed sensing and parallel imaging (k‐t SPARSE‐SENSE). Compared with reference, breath‐hold cine MRI, our eightfold accelerated real‐time cine MRI produced significantly worse qualitative grades (1–5 scale), but its image quality and temporal fidelity scores were above 3.0 (adequate) and artifacts and noise scores were below 3.0 (moderate), suggesting that acceptable diagnostic image quality can be achieved. Additionally, both eightfold accelerated real‐time cine and breath‐hold cine MRI yielded comparable left ventricular function measurements, with coefficient of variation <10% for left ventricular volumes. Our proposed eightfold accelerated real‐time cine MRI with k–t SPARSE‐SENSE is a promising modality for rapid imaging of myocardial function. J. Magn. Reson. Imaging 2013. © 2012 Wiley Periodicals, Inc.     

WT1 is a key regulator of podocyte function: reduced expression levels cause crescentic glomerulonephritis and mesangial sclerosis

Glomerular disease is one of the most common causes of end-stage renal failure. Increasing evidence suggests that these glomerulopathies are frequently caused by primary lesions in the renal podocytes. One of the major consequences of podocyte lesions is the accumulation of mesangial matrix in the glomerular basement membrane, a process called glomerulosclerosis. Mesangial sclerosis is one of the most consistent findings in Denys-Drash patients and can be caused by dominant mutations in the Wilms' tumor 1 gene (WT1). The underlying mechanism, however, is poorly understood. WT1 is expressed in the podocytes throughout life, but its function in this cell type is unknown. Combining Wt1-knockout and inducible yeast artificial chromosome transgenic mouse models, we demonstrate that reduced expression levels of WT1 result in either crescentic glomerulonephritis or mesangial sclerosis depending on the gene dosage. Strikingly, the two podocyte-specific genes nphs1 and podocalyxin are dramatically downregulated in mice with decreased levels of Wt1, suggesting that these two genes act downstream of Wt1. Taken together, our data provide genetic evidence that reduced levels of Wt1 are responsible for the pathogenesis of two distinct renal diseases and offer a molecular explanation for the increased occurrence of glomerulosclerosis in patients with WAGR syndrome.