Reasons to withhold intra-arterial thrombolysis in clinical practice

Background: In selected stroke centers intra-arterial thrombolysis (IAT) is used for the treatment of acute stroke patients presenting within 6hours of symptom onset. However, data about eligibility of acute stroke patients for IAT in clinical practice are very scarce. Methods: We collected prospectively data on indications advising for or against IAT of 230 consecutive stroke patients in a tertiary stroke center. Results: 76 patients (33.0%) presented within 3hours, 69 (30%) between 3 and 6hours of symptom onset and 85 (37%) later than 6hours. Arteriography was performed in 71 patients (31%) and IAT in 46 (20%). In 11 patients no or only peripheral branch occlusions were seen on arteriography and therefore IAT was not performed. In 9 patients the ICA was occluded and barred IAT and in five anatomical or technical difficulties made IAT impossible. 72 patients presenting within 6hours did not undergo arteriography and thrombolysis, mostly because of mild (n=44) or rapidly improving neurological deficits (n=13). Other reasons to withhold IAT were CT and/or clinical findings suggesting lacunar stroke due to small vessel occlusion (n=7), limiting comorbidty (n=7) and baseline international normalized ratio>1.7 (n=1). Conclusions: A third of the patients underwent diagnostic arteriography and one fifth received IAT. The most important reasons to withhold thrombolysis were presentation beyond the 6hours time window and mild or rapidly improving symptom

Degeneration of the cervical disc: histology compared with radiography and magnetic resonance imaging

Decisions about the treatment of neck pain are largely made on the basis of information gained from plain X-rays and magnetic resonance imaging (MRI), which are used routinely as part of preliminary investigation. We performed a descriptive cadaveric study to compare histology with radiography and MRI. We correlated plain radiography, disc height [Farfan index (FI)] and MRI findings with histology to assess the ability of radiology to detect significant pathologic lesions. The study included 52 motion segments from nine subjects over the age of 50, who underwent routine hospital autopsy. Disc degeneration was assessed by histology, radiography, disc height (FI: anterior disc height plus posterior disc height divided by anterioposterior diameter) and MRI using established grading systems. Most of the discs were classified radiologically as grade 1 (19/52), grade 2 (13/52), grade 3 (9/52) or grade 4 (3/52). Eight of the discs were graded as normal. The distribution of MRI grades was grade 0 (9/36), grade 1 (9/36), grade 2 (7/36), grade 3 (8/36) and grade 4 (3/36). Half of the discs (26/52) showed advanced (grade 4) degeneration histologically. FI correlated with histological grade (P=0.013), MRI grade (P=0.02) and radiological grade (P<0.001) of degeneration. Radiological and histological grade of degeneration showed a weak correlation (r=0.3, P=0.033). MRI correlated with overall histological grade (r=0.41, P=0.015, n=34). Histological features (e.g., tears, rim lesions, prolapse of nucleus material) were poorly recognised by MRI, which had a sensitivity for disc material prolapse and annulus tears of less than 40%. Our study showed that discs from patients over 50years are histologically severely degenerated; however, these changes may not be detected by conventional radiography and MR

Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial

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Reasons to withhold intra-arterial thrombolysis in clinical practice

BACKGROUND: In selected stroke centers intra-arterial thrombolysis (IAT) is used for the treatment of acute stroke patients presenting within 6 hours of symptom onset. However, data about eligibility of acute stroke patients for IAT in clinical practice are very scarce. METHODS: We collected prospectively data on indications advising for or against IAT of 230 consecutive stroke patients in a tertiary stroke center. RESULTS: 76 patients (33.0%) presented within 3 hours, 69 (30%) between 3 and 6 hours of symptom onset and 85 (37%) later than 6 hours. Arteriography was performed in 71 patients (31%) and IAT in 46 (20%). In 11 patients no or only peripheral branch occlusions were seen on arteriography and therefore IAT was not performed. In 9 patients the ICA was occluded and barred IAT and in five anatomical or technical difficulties made IAT impossible. 72 patients presenting within 6 hours did not undergo arteriography and thrombolysis, mostly because of mild (n = 44) or rapidly improving neurological deficits (n = 13). Other reasons to withhold IAT were CT and/or clinical findings suggesting lacunar stroke due to small vessel occlusion (n = 7), limiting comorbidty (n = 7) and baseline international normalized ratio > 1.7 (n = 1). CONCLUSIONS: A third of the patients underwent diagnostic arteriography and one fifth received IAT. The most important reasons to withhold thrombolysis were presentation beyond the 6 hours time window and mild or rapidly improving symptoms

О распределении свинца и хрома в угле основных рабочих пластов Алмазно-Марьевского геолого-промышленного района

Рассмотрены особенности распределения Pb та Cr в угольных пластах Алмазно- Марьевского геолого-промышленного района. Установлен характер распределения, выполнен расчет средневзвешенных концентраций в углях основных пластов и свит, выявлен состав типоморфной геохимической ассоциации Co и V с другими токсичными и потенциальными элементами в углях района. Исследования распределения свинца и хрома в углях основных рабочих пластов Алмазн

Climatically sensitive transfer of iron to maritime Antarctic ecosystems by surface runoff

Iron supplied by glacial weathering results in pronounced hotspots of biological production in an otherwise iron-limited Southern Ocean Ecosystem. However, glacial iron inputs are thought to be dominated by icebergs. Here we show that surface runoff from three island groups of the maritime Antarctic exports more filterable (<0.45 μm) iron (6–81 kg km−2 a−1) than icebergs (0.0–1.2 kg km−2 a−1). Glacier-fed streams also export more acid-soluble iron (27.0–18,500 kg km−2 a−1) associated with suspended sediment than icebergs (0–241 kg km−2 a−1). Significant fluxes of filterable and sediment-derived iron (1–10 Gg a−1 and 100–1,000 Gg a−1, respectively) are therefore likely to be delivered by runoff from the Antarctic continent. Although estuarine removal processes will greatly reduce their availability to coastal ecosystems, our results clearly indicate that riverine iron fluxes need to be accounted for as the volume of Antarctic melt increases in response to 21st century climate change

Non-B DB: a database of predicted non-B DNA-forming motifs in mammalian genomes

Although the capability of DNA to form a variety of non-canonical (non-B) structures has long been recognized, the overall significance of these alternate conformations in biology has only recently become accepted en masse. In order to provide access to genome-wide locations of these classes of predicted structures, we have developed non-B DB, a database integrating annotations and analysis of non-B DNA-forming sequence motifs. The database provides the most complete list of alternative DNA structure predictions available, including Z-DNA motifs, quadruplex-forming motifs, inverted repeats, mirror repeats and direct repeats and their associated subsets of cruciforms, triplex and slipped structures, respectively. The database also contains motifs predicted to form static DNA bends, short tandem repeats and homo(purine•pyrimidine) tracts that have been associated with disease. The database has been built using the latest releases of the human, chimp, dog, macaque and mouse genomes, so that the results can be compared directly with other data sources. In order to make the data interpretable in a genomic context, features such as genes, single-nucleotide polymorphisms and repetitive elements (SINE, LINE, etc.) have also been incorporated. The database is accessed through query pages that produce results with links to the UCSC browser and a GBrowse-based genomic viewer. It is freely accessible at http://nonb.abcc.ncifcrf.gov

CYP2C8 and CYP2C9 polymorphisms in relation to tumour characteristics and early breast cancer related events among 652 breast cancer patients

BACKGROUND: CYP2C8/9 polymorphisms may influence breast cancer-free survival after diagnosis due to their role in the metabolism of tamoxifen, paclitaxel, and other chemotherapy. cytochrome P450 (CYP)2C8/9 metabolise arachidonic acid to epoxyeicosatrienoic acids, which enhance migration and invasion in vitro and promote angiogenesis in vivo. We aimed to investigate the frequency of CYP2C8/9 polymorphisms in relation to breast tumour characteristics and disease-free survival. METHODS: A prospective series of 652 breast cancer patients from southern Sweden was genotyped for CYP2C8*3, CYP2C8*4, CYP2C9*2, and CYP2C9*3. Blood samples and questionnaires were obtained pre- and postoperatively. Clinical information and tumour characteristics were obtained from patients' charts and pathology reports. RESULTS: Frequencies of CYP2C8/9 polymorphisms were similar to healthy European populations. Significantly less node involvement (P=0.002) and fewer PR+ tumours (P=0.012) were associated with CYP2C8*4. Median follow-up was 25 months and 52 breast cancer-related events were reported. In a multivariate model, CYP2C8/9*3/*1*/*2/*1 was the only factor associated with increased risk for early events in 297 tamoxifen-treated, ER-positive patients, adjusted HR 2.54 (95%CI 1.11-5.79). The effect appeared to be driven by CYP2C8*3, adjusted HR 8.56 (95%CI 1.53-51.1). CONCLUSION: Polymorphic variants of CYP2C8/9 may influence breast tumour characteristics and disease-free survival in tamoxifen-treated patients

High-Throughput SuperSAGE for Digital Gene Expression Analysis of Multiple Samples Using Next Generation Sequencing

We established a protocol of the SuperSAGE technology combined with next-generation sequencing, coined “High-Throughput (HT-) SuperSAGE”. SuperSAGE is a method of digital gene expression profiling that allows isolation of 26-bp tag fragments from expressed transcripts. In the present protocol, index (barcode) sequences are employed to discriminate tags from different samples. Such barcodes allow researchers to analyze digital tags from transcriptomes of many samples in a single sequencing run by simply pooling the libraries. Here, we demonstrated that HT-SuperSAGE provided highly sensitive, reproducible and accurate digital gene expression data. By increasing throughput for analysis in HT-SuperSAGE, various applications are foreseen and several examples are provided in the present study, including analyses of laser-microdissected cells, biological replicates and tag extraction using different anchoring enzymes