Shape-Adaptive DCT for Denoising of 3D Scalar and Tensor Valued Images

During the last ten years or so, diffusion tensor imaging has been used in both research and clinical medical applications. To construct the diffusion tensor images, a large set of direction sensitive magnetic resonance image (MRI) acquisitions are required. These acquisitions in general have a lower signal-to-noise ratio than conventional MRI acquisitions. In this paper, we discuss computationally effective algorithms for noise removal for diffusion tensor magnetic resonance imaging (DTI) using the framework of 3-dimensional shape-adaptive discrete cosine transform. We use local polynomial approximations for the selection of homogeneous regions in the DTI data. These regions are transformed to the frequency domain by a modified discrete cosine transform. In the frequency domain, the noise is removed by thresholding. We perform numerical experiments on 3D synthetical MRI and DTI data and real 3D DTI brain data from a healthy volunteer. The experiments indicate good performance compared to current state-of-the-art methods. The proposed method is well suited for parallelization and could thus dramatically improve the computation speed of denoising schemes for large scale 3D MRI and DTI.     

Development of a time-resolved immunofluorometric assay for quantifying platelet-derived microparticles in human plasma

Platelet-derived microparticles (PMPs) are considered a marker of platelet activation. They vary considerably in size, and flow cytometry, the predominant method used to assay PMPs, is only detecting larger PMPs (> 0.1 μm).

We describe here a method that quantifies the amount of PMP-located GPIIb antigen in detergent-treated platelet-free plasma (PPP) by means of a one-step time-resolved immunofluorometric assay (TR-IFMA). This assay uses a streptavidin-coated microwell plate and two different monoclonal antibodies to GPIIb (CD41), one conjugated to biotin and the other labeled with europium ion. A wide linear range standard curve with low background and a high sensitivity was obtained. Pre-assay ultracentrifugation or filtration of PPP extensively reduced the fluorometric signal, indicating that the GPIIb antigen is mainly particle-located. A strong correlation between the amount of GPIIb and PMP as detected by flow cytometry was found. Consequently, the assay can be used to study PMP-related phenomena and, in contrast to flow cytometry, can be used on frozen samples and is independent of PMP size.     

Clonal Distribution of Invasive Neisseria meningitidis Isolates from the Norwegian County of Telemark, 1987 to 1995

Forty-two Neisseria meningitidis isolates were obtained from patients with meningococcal disease in the Norwegian county of Telemark (January 1987 to March 1995), and all were compared by PCR amplicon restriction endonuclease analysis (PCR-AREA) of the dhps gene, chromosomal DNA fingerprinting, and serological analysis. PCR-AREA divided the isolates into 11 classes, of which 4, comprising 15, 8, 6, and 2 isolates, were clonal while the remaining 8 classes were genetically heterogeneous or contained only 1 isolate. Three of the four clonal classes could be tentatively equated with recognized epidemic clones (ET5, ET37, and cluster A4) on the basis of their phenotypic characteristics, while the remaining clone appears to be new. There were significant differences in the geographical distribution of clones, with class 1 (ET5-like) isolates significantly overrepresented in rural parts of Telemark. Class 1 (ET5-like) isolates occurred throughout the study period and were dominant in 1987. Class 2 (ET37-like) isolates occurred from 1988 to 1992, and class 3 isolates (with no recognizable ET affinities) were found only in 1991 and 1992.Meningococcal disease occurs in the form of sporadic cases, local outbreaks, and epidemics and has a high mortality. Much attention has been paid to methods for typing meningococcal strains in order to trace and control outbreaks and elucidate the global epidemiology of the bacterium, and this has generated a considerable variety of typing methods. The “gold standard” method is isoenzyme electrophoresis (ET typing) (16). This method, which compares electrophoretic polymorphisms in multiple enzymes, defines epidemic clones of Neisseria meningitidis, provides an estimate of genetic similarity, and has provided the basis for inference of the genetic population structure of N. meningitidis. In the clinical setting, a typing system based on serogrouping (capsular polysaccharides), serotyping and subtyping (class 1, 2, and 3 outer membrane proteins), and sulfonamide resistance is more frequently used (6). Although this method may be a useful guide to the clonal affinities of meningococcal strains when applied locally, on a global basis serogroup and, to a lesser extent, serotype are poorly correlated with genetic relatedness (3). More recently, genetic methods, such as whole-genome DNA fingerprinting (12, 18), random amplification of polymorphic DNA (21), repetitive element-based PCR (20), and restriction fragment length polymorphism (RFLP) analysis of PCR products (7, 10), have been successfully applied in epidemiological studies of N. meningitidis. Whole-genome DNA fingerprinting, though useful for tracing outbreak strains, is unsuitable for classification because the restriction pattern is too complex, but other DNA-based methods that generate simpler patterns are more promising.We have previously described a method (PCR amplicon restriction endonuclease analysis [PCR-AREA]) for PCR-based RFLP analysis of the highly polymorphic chromosomal dhps gene, which determines resistance or sensitivity to sulfonamides in N. meningitidis (10). To evaluate PCR-AREA as a classification method, and in order to study the clonal distribution of meningococcal strains in the Norwegian county of Telemark, we have used PCR-AREA, in combination with DNA fingerprinting and serogroup, serotype and subtype, and sulfonamide resistance determinations, to compare 42 strains isolated from patients with meningococcal disease. This represents all primary cases of meningococcal disease in Telemark from January 1987 to March 1995.     

Prioritization and patients' rights: Analysing the effect of a reform in the Norwegian hospital sector

The right to equal treatment, irrespective of age, gender, ethnicity, socio-economic status and place of residence, is an important principle for several health care systems. A reform of the Norwegian hospital sector of 2002 may be used as a relevant experiment for investigating whether centralization of ownership and management structures will lead to more equal prioritization practices over geographical regions. One concern was variation in waiting times across the country. The reform was followed up in subsequent years by some other policy initiatives that also aimed at reducing waiting lists. We measure prioritization practice by a method that takes departure in recommended maximum waiting times from medical guidelines. We merge the information from the guidelines with individual patient data on actual waiting times for the period 1999–2005. This way we can monitor whether each patient in the available register of actual hospital visits has waited shorter or longer than what is considered medically acceptable by the guideline. The results indicate no equalization between the five new health regions, but we find evidence of more equal prioritization within four of the health regions. Our method of measuring prioritizations allows us to analyse how prioritization practice evolved over time after the reform, thus covering some further initiatives with the same objective. The results indicate that an observed reduction in waiting times after the reform have favoured patients of lower prioritization status, something we interpret as a general worsening of prioritization practices over time.     

Evaluation of the probes 2',7'-dichlorofluorescin diacetate,luminol, and lucigenin as indicators of reactive species formation

This study attempts to provide a critical assessment of three different common approaches to identifying teactive species formed in biological systems: the 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay, and the luminol- and lucigenin-amplified chemiluminescence assays. There have been several contradictory reports about the specificity of these methods. Our results show that DCFH is oxidized to the fluorescent compound 2',7'-dichlorofluorescin (DCF) in human neutrophils exposed to the following compounds: Aroclor (A)1242, hydrogen peroxide (H(2)O(2)), nitric oxide (NO), and FeSO(4). Use of a cell-free DCFH system showed increased formation of DCF by peroxynitrite (ONOO(-)), horseradish peroxidase (HRP) alone, and HRP in combination with H(2)O(2), FeSO(4) alone, and a mixture of FeSO(4) and H(2)O(2). The hydroxyl radical (z.rad;OH) scavenger formate and the iron ion chelator deferoxamine reduced the DCF formation induced by FeSO(4) in combination with H(2)O(2). DCFH was insensitive to NO and H(2)O(2) in the cell-free system. In the presence of neutrophils, the A1242-induced luminol chemiluminescence was decreased by the superoxide dismutase inhibitor diethyldithiocarbamic acid (DDC) and the myeloperoxidase inhibitor salicylhydroxamic acid (SHA). Exposure of the neutrophils to NO, FeSO(4), or H(2)O(2) alone did not have any effect. A1242-induced lucigenin chemiluminescence in the neutrophils was increased slightly by DDC, but was not affected by SHA, NO, FeSO(4), or H(2)O(2). In conclusion, we suggest that the DCF assay is only suitable for measurements of ONOO(-), H(2)O(2) in combination with cellular peroxidases, and z.rad;OH. Luminol is sensitive towards HOCl, while lucigenin is oxidized by O(2)z.rad;(-).     

Antibiotic sensitivity still prevails in Norwegian blood culture isolates

We describe the antimicrobial susceptibility of bacteraemia isolates from Norway. From March 1998 to February 1999, four university hospitals covering all parts of Norway collected their first 10 isolates each month. Minimal inhibitory concentrations were determined for: Enterobacteriaceae (n=192), staphylococci (n=89) and Streptococcus pneumoniae (n=69) using the Etest. NCCLS breakpoints were used. About 20% of all blood culture isolates in Norway in this period were investigated. Compared with countries outside Scandinavia antibiotic sensitivity still prevails. Only minor differences in resistance were found between participating hospitals, between hospital departments and between hospital- and community-acquired pathogens. The prudent use of antibiotics in Norway may contribute to the fact that antibiotic resistance still remains low in the most common bacterial pathogens causing bloodstream infections.     

Neoadjuvant cisplatin-methotrexate chemotherapy for invasive bladder cancer -- Nordic cystectomy trial 2

BACKGROUND: In the first Nordic cystectomy trial (1986-1989) a chemotherapy combination of cisplatin-doxorubicin and external radiation seemed to improve the long-term survival after cystectomy in patients with stage T3-T4a bladder carcinomas. The aim of this study was to investigate if solely neoadjuvant chemotherapy could influence survival in patients with advanced urothelial bladder cancer undergoing cystectomy. METHODS: The study (1991-1997) recruited 317 patients with T2-T4aNXM0 urothelial bladder tumours. The patients were randomly allocated to three courses of cisplatin-methotrexate or no pretreatment before cystectomy, eight were subsequently excluded due to protocol violation. RESULTS: Chemotherapy according to protocol was administered to 74% (115/155) of the patients in the experimental arm. No chemotherapy related mortality was observed. Of remaining patients in the experimental arm, 14 did not receive any chemotherapy, nine discontinued after one course and 14 after two courses due to side effects. Median follow-up time among censored patients was 5.3 years. Estimated 5-year overall survival was 53% in the experimental arm and 46% in the control arm (n.s. log-rank test). The proportion of patients with pathological stage pT0 was 26.4% in the experimental arm and 11.5% in the control arm (p = 0.001). Risk of locoregional relapse and distant metastases was similar in the study arms. CONCLUSIONS: The chemotherapy regimen was well tolerated. Despite substantial downstaging no statistically significant survival benefit with the neoadjuvant therapy could be seen after 5 years of follow-up.     

A protocol for angiographic embolization in exsanguinating pelvic trauma: a report on 31 patients

Background The indication for acquiring angiographic embolization in the initial treatment of severe pelvic fractures is controversial. We describe the characteristics and outcome of 31 patients with traumatic pelvic bleeding who underwent percutaneous angiography with embolization according to a standardized protocol.

Patients and methods During an 8.5-year period, 1,260 patients were treated for pelvic trauma. We performed a prospective registration of the 46 patients who underwent angiography, and report the 31 patients who had signs of significant arterial injury on angiography, necessitating embolization.

Results The rate of significant arterial injury after pelvic trauma was 2.5%. All patients had been subjected to high-energy injuries and all were severely injured as measured by the Injury Severity Score: 41 (17-66). Pelvic arterial injury was observed with all types of pelvic trauma, including isolated acetabular (4/31) and sacral fractures (3/31). The internal iliac artery or its branches was injured in 28 of 31 patients. Survival rate after embolization was 84%, and correlated inversely with increasing patient age. None of the patients died of bleeding.

Interpretation Our findings show that significant pelvic arterial injuries occur in a minority of patients after pelvic trauma, and predominantly affect patients with multiple high-energy injuries regardless of fracture type. The effect of angiographic embolization was good.