C-arm orbits for metal artifact avoidance (MAA) in cone-beam CT.

Metal artifacts present a challenge to cone-beam CT (CBCT) image-guided surgery, obscuring visualization of metal instruments and adjacent anatomy-often in the very region of interest pertinent to the imaging/surgical tasks. We present a method to reduce the influence of metal artifacts by prospectively defining an image acquisition protocol-viz., the C-arm source-detector orbit-that mitigates metal-induced biases in the projection data. The metal artifact avoidance (MAA) method is compatible with simple mobile C-arms, does not require exact prior information on the patient or metal implants, and is consistent with 3D filtered backprojection (FBP), more advanced (e.g. polyenergetic) model-based image reconstruction (MBIR), and metal artifact reduction (MAR) post-processing methods. The MAA method consists of: (i) coarse localization of metal objects in the field-of-view (FOV) via two or more low-dose scout projection views and segmentation (e.g. a simple U-Net) in coarse backprojection; (ii) model-based prediction of metal-induced x-ray spectral shift for all source-detector vertices accessible by the imaging system (e.g. gantry rotation and tilt angles); and (iii) identification of a circular or non-circular orbit that reduces the variation in spectral shift. The method was developed, tested, and evaluated in a series of studies presenting increasing levels of complexity and realism, including digital simulations, phantom experiment, and cadaver experiment in the context of image-guided spine surgery (pedicle screw implants). The MAA method accurately predicted tilted circular and non-circular orbits that reduced the magnitude of metal artifacts in CBCT reconstructions. Realistic distributions of metal instrumentation were successfully localized (0.71 median Dice coefficient) from 2-6 low-dose scout views even in complex anatomical scenes. The MAA-predicted tilted circular orbits reduced root-mean-square error (RMSE) in 3D image reconstructions by 46%-70% and 'blooming' artifacts (apparent width of the screw shaft) by 20-45%. Non-circular orbits defined by MAA achieved a further ∼46% reduction in RMSE compared to the best (tilted) circular orbit. The MAA method presents a practical means to predict C-arm orbits that minimize spectral bias from metal instrumentation. Resulting orbits-either simple tilted circular orbits or more complex non-circular orbits that can be executed with a motorized multi-axis C-arm-exhibited substantial reduction of metal artifacts in raw CBCT reconstructions by virtue of higher fidelity projection data, which are in turn compatible with subsequent MAR post-processing and/or polyenergetic MBIR to further reduce artifacts.

3D-2D image registration for target localization in spine surgery: investigation of similarity metrics providing robustness to content mismatch.

In image-guided spine surgery, robust three-dimensional to two-dimensional (3D-2D) registration of preoperative computed tomography (CT) and intraoperative radiographs can be challenged by the image content mismatch associated with the presence of surgical instrumentation and implants as well as soft-tissue resection or deformation. This work investigates image similarity metrics in 3D-2D registration offering improved robustness against mismatch, thereby improving performance and reducing or eliminating the need for manual masking. The performance of four gradient-based image similarity metrics (gradient information (GI), gradient correlation (GC), gradient information with linear scaling (GS), and gradient orientation (GO)) with a multi-start optimization strategy was evaluated in an institutional review board-approved retrospective clinical study using 51 preoperative CT images and 115 intraoperative mobile radiographs. Registrations were tested with and without polygonal masks as a function of the number of multistarts employed during optimization. Registration accuracy was evaluated in terms of the projection distance error (PDE) and assessment of failure modes (PDE > 30 mm) that could impede reliable vertebral level localization. With manual polygonal masking and 200 multistarts, the GC and GO metrics exhibited robust performance with 0% gross failures and median PDE < 6.4 mm (±4.4 mm interquartile range (IQR)) and a median runtime of 84 s (plus upwards of 1-2 min for manual masking). Excluding manual polygonal masks and decreasing the number of multistarts to 50 caused the GC-based registration to fail at a rate of >14%; however, GO maintained robustness with a 0% gross failure rate. Overall, the GI, GC, and GS metrics were susceptible to registration errors associated with content mismatch, but GO provided robust registration (median PDE = 5.5 mm, 2.6 mm IQR) without manual masking and with an improved runtime (29.3 s). The GO metric improved the registration accuracy and robustness in the presence of strong image content mismatch. This capability could offer valuable assistance and decision support in spine level localization in a manner consistent with clinical workflow.

Cytokine (IL-6) and chemokine (IL-8) gene polymorphisms among rheumatoid arthritis patients in Taiwan.

OBJECTIVE: The involvement of cytokines and chemokines in the pathogenesis of rheumatoid arthritis (RA) is well studied; however, the genetic bases behind this is not well understood. The aim of this study was to examine whether -572 G/C polymorphism in the IL-6 gene and 2767 A/G polymorphism in the 3'-untranslated region (UTR) of the IL-8 gene are associated with rheumatoid arthritis (RA). METHODS: We enrolled 199 RA patients and 130 normal controls. Polymerase chain reaction was used to identify the IL-6 -572G/C and IL-8 3'-UTR 2767A/G polymorphisms. The relationships between clinical manifestations of RA and the polymorphisms of each gene were investigated by comparing the genotypes among RA patients with different clinical variables. RESULTS: We found no significant difference in the genotypic and allelic frequencies of the single nucleotide polymorphisms of IL-6 and IL-8 genes between RA patients and controls. Clinical characteristics such as age at onset, rheumatoid factor positivity, joint erosion and extra-articular manifestations were compared among patients with different genotypes of the IL-6 and IL-8 genes. We found that patients with IL-8 3'-UTR 2767AA genotype had a significantly younger age of onset of RA than patients without that genotype. CONCLUSION: The IL-6 -572 G/C and IL-8 3'-UTR 2767A/G polymorphisms are not associated with the risk of developing rheumatoid arthritis. However, the finding that patients with IL-8 3'-UTR 2767AA developed RA at a younger age suggests that this genotype may influence the etiopathology of RA in patients in Taiwan. Therefore, further single nucleotide polymorphism studies of this 3'UTR region may give more novel findings and understanding of the genetic basis of rheumatoid arthritis.

Using wound bed preparation to heal a malignant fungating wound: a single case study.

Full healing was achieved within eight weeks in a malignant fungating wound using the principles of the TIME paradigm. This concept appears to provide a structured and systematic approach for managing such non-healing wounds.

Interleukin-1 receptor antagonist gene polymorphism in Taiwanese patients with gout.

OBJECTIVE: The purpose of this study was to examine whether interleukin-1 receptor antagonist (IL-1Ra) gene polymorphism is a marker of susceptibility to or of the clinical characteristics of gout in Taiwanese patients. METHODS: 196 Taiwanese patients with gout and 103 unrelated normal healthy control subjects living in central Taiwan were studied. Polymorphism of the gene for IL-1Ra was typed from genomic DNA. Allelic frequencies and carriage rates were compared between gout patients and control subjects. The relationship between IL-1Ra genotypes and the clinical characteristics of gout was also evaluated. RESULTS: No significant differences were observed in genetic and allelic frequencies of the IL-1Ra gene polymorphism between patients with gout and healthy control subjects. Furthermore, we did not detect any association of IL-1Ra genotype with the clinical and laboratory profiles in patients with gout. CONCLUSION: The results from the present study suggest that the interleukin-1 receptor antagonist gene polymorphism is not a genetic marker of susceptibility to gout for Taiwanese. Furthermore, our study also suggests that the IL-1Ra gene polymorphism is unrelated to the clinical characteristics of gout.

Arterial lesions in severe lower limb ischaemia: a prospective study of 100 consecutive ischaemic limbs in a Hong Kong Chinese population.

BACKGROUND: The pattern and distribution of arterial lesions in a local Chinese population were studied to assess the feasibility of reconstruction and the possibility of avoiding major amputation of ischaemic limbs. METHOD: Between March 1995 and August 1997, 90 consecutive patients with 100 severely ischaemic lower limbs and their arteriograms were analysed. There were 48 female and 42 male patients with a mean age of 72 years. All the patients were in fair general health, did not have foot pulses and were willing to undergo major arterial reconstruction. Ten patients had bilateral limb ischaemia and 94 of the ischaemic limbs were affected by rest pain with or without ulcer and/or gangrene. The remaining six patients had debilitating claudication. These lesions were classified into low-grade (less than 50% stenosis), high-grade (50-90% stenosis) and critical (> 90% stenosis to occlusion). RESULTS: Critically stenotic or occlusive lesions were present in 16% of aorto-iliac segments; 76% of femoropopliteal arteries; and 82% of trifurcation and infrapopliteal segments. In at least 27 patients one of the two main foot arteries was also severely diseased. The present analysis suggested that 79 of these ischaemic limbs had reconstructable lesions. Sixteen were not suitable for intervention and in five patients the reconstructability was uncertain radiologically. CONCLUSION: Contrary to local belief, the majority of patients in the Chinese community with severe lower limb ischaemia without foot pulses would have technically reconstructable arterial lesions and could benefit from a revascularization procedure.

Pancreatic tuberculosis: case reports and review of the literature.

Tuberculosis affecting the pancreas is rare. Its occurrence may pose a diagnostic problem in differentiating it from carcinoma of the pancreas. Two cases of tuberculosis affecting the pancreas are reported, illustrating the value of fine needle aspiration in such a situation. The response of the disease to antituberculous drugs was slow, but sure.

Analysis of total IgE and allergen-specific IgE antibody levels of allergic children in Taiwan.

With advances in technology, several in vitro screening tests such as MAST and CAP system have been used for analyzing the allergens involved in allergic diseases such as bronchial asthma (BA), allergic rhinitis (AR), atopic dermatitis (AD) and urticaria. In this study, CAP system (Pharmacia, Sweden) was used to screen the prevalence of allergens responsible for these atopic diseases. A total of 392 children were enrolled in this study retrospectively, all these atopic children visited the allergy clinic of the Department of Pediatrics, National Taiwan University Hospital during the period March 1995 and August 1995. Our results showed: (1) Among these 392 allergic children, included 82 BA, 70 AR, 22 AD, 156 BA + AR. 8 BA + AD, 12 AR + AD, and 42 AD + AR + AD: (2) House dust mites (Dermatophagoides pteronyssinus: D. p and Dermatophagoides farinae: D. f) are the most common allergens triggering atopic disease in the Taiwan area. (3) Total IgE level is the highest in three combined allergic disease (BA + AR + AD) [2179.9 +/- 504.2KU/L] and lowest in single disease (AR) [503.1 +/- 84.8 KU/L]. Mite-specific IgE (D. p + D. f-specific IgE) concentration is also the highest in three combined disease (BA + AR + AD) [499.1 +/- 86.0KU/L] and lowest in AR [159.5 +/- 47.5 KU/L], (4) elevated specific IgE antibody to egg white and milk were found in 68.4% and 47.4% of patients with AD and/or urticaria. In conclusion, these data suggest that house dust mites, are the most important allergens in respiratory allergy as well as in atopic dermatitis, while food allergens play relatively important roles only in skin allergy. Furthermore, the highest IgE level was noted in children with combined allergic diseases.

Arterial reconstruction for lower limb ischaemia in Hong Kong Chinese.

BACKGROUND: Lower limb ischaemia due to peripheral arterial disease is uncommon in Chinese people, and few arterial bypass operations have been performed. The management of a consecutive series of patients who were admitted to our department with severe lower limb ischaemis between March 1990 and October 1996 is reported here. METHODS: A total of 91 primary arterial bypass operations were performed for 83 patients (eight patients had bilateral, or two procedures). Of these, 84 operations were for foot salvage and seven operations were for debilitating claudication. There were 80 infra-inguinal bypasses, 10 of which required additional femoro-femoral crossover grafts to improve in-flow. The remaining 11 bypass procedures were performed for aorto-iliac occlusion, which included aortobifemoral bypass (5), axillobifemoral bypass (3) and cross-femoral bypass (3) grafts. There were 46 male and 37 female patients, with a median age of 70 years (36-94). RESULTS: Six patients died (6.6%) postoperatively, all of whom were in the foot salvage group. The overall cumulative foot salvage rate and graft patency was 84 and 56%, respectively, at 5 years. CONCLUSIONS: These results justified the use of the same aggressive approach that was adopted in Western countries for the treatment of peripheral arterial disease, which seemed to be an emerging problem in Hong Kong.

Serum osteocalcin levels of normal children in Taiwan.

Osteocalcin is mainly secreted by osteoblasts, and then diffuses into blood which can be detected by several experimental methods. This study determined the osteocalcin level by solid phase fluorescent immunosorbent assay (Pharmacia CAP; Sweden), a well-established and accurate laboratory method for determining the minor concentration of substances in blood. A total of 332 healthy children were enrolled in the study, including 176 boys and 156 girls ranging in age from one to fifteen years. It was concluded that (1) quantitative osteocalcin (OCs) value varies between 30.2 to 41.0 ng/ml; (2) there is an incremental tendency in both sexes until puberty; (3) girls generally have a higher osteocalcin level than boys before mid-puberty (2-12 years old). The differences are statistically significant.

Affinity maturation without germinal centres in lymphotoxin-alpha-deficient mice.

Affinity maturation by somatic hypermutation is thought to occur within germinal centres. Mice deficient in lymphotoxin-alpha (LT alpha-/- mice) have no lymph nodes or Peyer's patches, and fail to form germinal centres in the spleen. We tested whether germinal centres are essential for maturation of antibody responses to T-cell-dependent antigens. LT alpha-/- mice immunized with low doses of (4-hydroxy-3-nitrophenyl)acetyl-ovalbumin (NP-OVA) showed dramatically impaired production of high-affinity anti-NP IgG1. However, LT alpha-/- mice immunized with high doses of NP-OVA, even though they failed to produce germinal centres, manifested a high-affinity anti-NP IgG1 response similar to wild-type mice. Furthermore, when LT alpha-/- mice were multiply immunized with high doses of NP-OVA, the predominantly expressed anti-NP VH gene segment VH186.2 showed somatic mutations typical of affinity maturation. Thus, B-cell memory and affinity maturation are not absolutely dependent on the presence of germinal centres.

Impact of point-of-care testing on patients' length of stay in a large emergency department.

We prospectively investigated whether routine use of a point-of-care testing (POCT) device by nonlaboratory operators in the emergency department (ED) for all patients requiring the available tests could shorten patient length of stay (LOS) in the ED. ED patient LOS, defined as the length of time between triage (initial patient interview) and discharge (released to home or admitted to hospital), was examined during a 5-week experimental period in which ED personnel used a hand-held POCT device to perform Na, K, Cl, glucose (Gluc), and blood urea nitrogen (BUN) testing. Preliminary data demonstrated acceptable accuracy of the hand-held device. Patient LOS distribution during the experimental period was compared with the LOS distribution during a 5-week control period before institution of the POCT device and with a 3-week control period after its use. Among nearly 15 000 ED patient visits during the study period, 4985 patients (2067 during the experimental period and 2918 during the two control periods) had at least one Na, K, Cl, BUN, or Gluc test ordered from the ED. However, no decrease in ED LOS was observed in the tested patients during the experimental period. Median LOS during the experimental period was 209 min vs 201 min for the combined control periods. Stratifying patients by presenting condition (chest pain, trauma, etc.), discharge/admit status, or presence/absence of other central laboratory tests did not reveal a decrease in patient LOS for any patient subgroup during the experimental period. From these observations, we consider it unlikely that routine use of a hand-held POCT device in a large ED such as ours is sufficient by itself to impact ED patient LOS.

Studies of the biosynthesis of 3,6-dideoxyhexoses: molecular cloning and characterization of the asc (ascarylose) region from Yersinia pseudotuberculosis serogroup VA.

The 3,6-dideoxyhexoses are found in the lipopolysaccharides of gram-negative bacteria, where they have been shown to be the dominant antigenic determinants. Of the five 3,6-dideoxyhexoses known to occur naturally, four have been found in various strains of Salmonella enterica (abequose, tyvelose, paratose, and colitose) and all five, including ascarylose, are present among the serotypes of Yersinia pseudotuberculosis. Although there exists one report of the cloning of the rfb region harboring the abequose biosynthetic genes from Y. pseudotuberculosis serogroup HA, the detailed genetic principles underlying a 3,6-dideoxyhexose polymorphism in Y. pseudotuberculosis have not been addressed. To extend the available information on the genes responsible for 3,6-dideoxyhexose formation in Yersinia spp. and facilitate a comparison with the established rfb (O antigen) cluster of Salmonella spp., we report the production of three overlapping clones containing the entire gene cluster required for CDP-ascarylose biosynthesis. On the basis of a detailed sequence analysis, the implications regarding 3,6-dideoxyhexose polymorphism among Salmonella and Yersinia spp. are discussed. In addition, the functional cloning of this region has allowed the expression of Ep (alpha-D-glucose cytidylyltransferase), Eod (CDP-D-glucose 4,6-dehydratase), E1 (CDP-6-deoxy-L-threo-D-glycero-4- hexulose-3-dehydrase), E3 (CDP-6-deoxy-delta 3,4-glucoseen reductase), Eep (CDP-3,6-dideoxy-D-glycero-D- glycero-4-hexulose-5-epimerase), and Ered (CDP-3,6-dideoxy-L-glycero-D-glycero-4-hexulose-4-reductase), facilitating future mechanistic studies of this intriguing biosynthetic pathway.

CDP-6-deoxy-delta 3,4-glucoseen reductase from Yersinia pseudotuberculosis: enzyme purification and characterization of the cloned gene.

The 3,6-dideoxyhexoses, usually confined to the cell wall lipopolysaccharide of gram-negative bacteria, are essential to serological specificity and are formed via a complex biosynthetic pathway beginning with CDP-D-hexoses. In particular, the biosynthesis of CDP-ascarylose, one of the naturally occurring 3,6-dideoxyhexoses, consists of five enzymatic steps, with CDP-6-deoxy-delta 3,4-glucoseen reductase (E3) participating as the key enzyme in this catalysis. This enzyme has been previously purified from Yersinia pseudotuberculosis by an unusual procedure (protocol I) including a trypsin digestion step (O. Han, V.P. Miller, and H.-W. Liu, J. Biol. Chem. 265:8033-8041, 1990). However, the cloned gene showed disparity with the expected gene characteristics, and upon expression, the resulting gene product exhibited no E3 activity. These findings strongly suggested that the protein isolated by protocol I may have been misidentified as E3. A reinvestigation of the purification protocol produced a new and improved procedure (protocol II) consisting of DEAE-Sephacel, phenyl-Sepharose, Cibacron blue A, and Sephadex G-100 chromatography, which efficiently yielded a new homogeneous enzyme composed of a single polypeptide with a molecular weight of 39,000. This highly purified protein had a specific activity nearly 8,000-fold higher than that of cell lysates, and more importantly, the corresponding gene (ascD) was found to be part of the ascarylose biosynthetic cluster. Presented are the identification and confirmation of the E3 gene through cloning and overexpression and the culminating purification and unambiguous assignment of homogeneous E3. The nucleotide and translated amino acid sequences of the genuine E3 are also presented.

Cofactor characterization and mechanistic studies of CDP-6-deoxy-delta 3,4-glucoseen reductase: exploration into a novel enzymatic C-O bond cleavage event.

The CDP-6-deoxy-delta 3,4-glucoseen reductase (E3) is a NADH-dependent enzyme which catalyzes the key reduction of the C-3 deoxygenation step during the formation of CDP-ascarylose, a 3,6-dideoxyhexose found in the lipopolysaccharide of Yersinia pseudotuberculosis. This highly purified enzyme is also a NADH oxidase capable of mediating the direct electron transfer from NADH to O2, forming H2O2. While previous work showed that E3 contains no common cofactor, one FAD and one plant ferredoxin type [2Fe-2S] center were found in this study to be associated with each molecule of E3. The iron-sulfur center is essential for E3 activity since bleaching of the [2Fe-2S] center leads to inactive enzyme. These results suggest that E3 employs a short electron-transport chain composed of both FAD and the iron-sulfur center to shuttle electrons from NADH to its acceptor. The order of electron flow, as indicated by EPR measurement with partially reduced E3, starts with hydride reduction of FAD by NADH. The iron-sulfur cluster, receiving electrons one at a time from the reduced flavin, relays the reducing equivalents via another iron-sulfur center in the active site of E1 to its final acceptor, the E1-bound PMP-glucoseen adduct. The participation of a one-electron-carrying iron-sulfur center in this reduction is advantageous since both electrons are dispatched from the same redox state of the prosthetic group, allowing electrons of equal energy to be delivered to the final acceptor.(ABSTRACT TRUNCATED AT 250 WORDS)

The POEMS syndrome among Chinese: association with Castleman's disease and some immunological abnormalities.

POEMS or Crow-Fukase syndrome is a multisystemic, clinically malignant disorder of obscure etiology. Peripheral neuropathy and plasma cell dyscrasia are central features. The authors now report 7 Chinese patients with this syndrome in which PCD or paraproteinemia were absent in 6, and 2 had a lymph node histology resembling that of hyaline-vascular Castleman's disease. Immunological abnormalities consisted of either increased or decreased numbers of B- and T-cells in 2 cases, and an elevated OKT4/OKT8 ratio with paradoxical dissociation of the lymphocyte transformations to various concentrations and types of mitogens in 1 case. This suggests that the underlying abnormalities of POEMS syndrome are heterogeneous and that it may be an immunologically related syndrome of varying etiology.