Distinct X chromosomal rearrangements in four haemophilia B patients with entire F9 deletion.

INTRODUCTION: Haemophilia B is an X-linked bleeding disorder caused by a coagulation factor IX gene (F9) abnormality. Numerous F9 defects have been identified to date; however, only a few with an entire F9 deletion have been reported in detail. AIM: To elucidate the cause of severe haemophilia B, we investigated the precise X chromosome abnormalities in four Japanese patients who did not show all amplifications in F9-specific PCR. METHODS: We analysed the patient's genomic DNA using Multiplex ligation-dependent probe amplification (MLPA). To assess the extent of any deletions, we further performed mapping PCRs, inverse PCRs or long-range PCRs and direct sequencing analyses of the X chromosome. RESULTS: We detected entire F9 deletions in four haemophilia B patients and identified the precise deleted regions of the X chromosome including F9. Patient 1 had a 149-kb deletion with breakpoints 90-kb upstream and 30-kb downstream from F9. Patients 2 and 3 showed 273-kb and 1.19-Mb deletions respectively. Patient 4 had two deleted regions: a 1663-bp deletion 1.34-Mb upstream from F9 and a 7.2-Mb deletion including F9. These distinct breakpoints found in four different patients suggest that the mechanism of X chromosome deletion may be different between individuals. Non-allelic homologous recombination (NAHR), microhomology-mediated break-induced replication (MMBIR) or fork stalling and template switching (FoSTeS) may occur in respective X chromosomes of the four haemophilia B patients analysed. CONCLUSIONS: We identified diverse X chromosomal rearrangements in four haemophilia B patients, which might be caused by distinct mechanisms of genomic rearrangement.

Vascular supply with angio-CT for superselective intra-arterial chemotherapy in advanced maxillary sinus cancer.

Recently popularised, the combined angiography and CT (angio-CT) system is useful for correctly identifying the feeding arteries and their perfusion in various organs. We applied this system for advanced maxillary cancer to expose its feeding arteries and their supplying territories. In addition to the maxillary artery, extramaxillary feeding arteries were usually observed, including the ophthalmic, accessory meningeal, facial, transverse facial and ascending palatine arteries. These extramaxillary feeding arteries exhibited uniform tendencies, depending on the site of extramaxillary tumour extension.

Phase II trial of S-1 and cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer.

BACKGROUND: To assess the efficacy and safety of S-1 and cisplatin with concurrent thoracic radiation for unresectable stage III non-small-cell lung cancer (NSCLC). METHODS: Eligible patients were 20-74 years old and had histologically or cytologically confirmed NSCLC, a performance status of 0-1, and no prior chemotherapy. Patients were treated with cisplatin (60 mg m(-2) on day 1) and S-1 (orally at 40 mg m(-2) per dose, b.i.d., on days 1-14), with the treatment repeated every 4 weeks for four cycles. Beginning on day 2, a 60-Gy thoracic radiation dose was delivered in 30 fractions. RESULTS: Of 50 patients, 48 were eligible. Partial response was observed in 42 patients (87.5%; 95% CI: 79.1-96.9%). This regimen was well tolerated. Common toxicities included grade 3/4 neutropenia (32%), grade 3/4 leukopenia (32%), grade 3/4 thrombocytopenia (4%), grade 3 febrile neutropenia (6%), grade 3 oesophagitis (10%), and grade 3 pneumonitis (5%). Median progression-free survival was 12.0 months and median overall survival was 33.1 months. The 1- and 2-year survival rates were 89.5 and 56%, respectively. CONCLUSION: This chemotherapy regimen with concomitant radiotherapy is a promising treatment for locally advanced NSCLC because of its high response rates, good survival rates, and mild toxicities.

Bone marrow transplantation from unrelated donors for patients with adult T-cell leukaemia/lymphoma.

Adult T-cell leukaemia/lymphoma (ATLL) is a highly aggressive haematological malignancy. More than 40 cases of ATLL treated by allogeneic bone marrow transplantation (BMT) from sibling donors have been reported, while there have been only a few cases of unrelated BMT for treatment of this disease. We began performing allogeneic BMT from unrelated donors in 1999 to improve the outcome of ATLL patients with no suitable sibling donors. Eight ATLL patients underwent unrelated BMT; five received the conventional conditioning regimen consisting of cyclophosphamide and total body irradiation, while three received a reduced-intensity preparative regimen. Two patients died due to encephalopathy of unknown aetiology on days 10 and 35, and one patient died due to progression of ATLL 25 months after BMT. Five patients are currently alive and disease-free at a median of 20 months after BMT. Proviral human T-lymphotropic virus type-I (HTLV-I) DNA load in peripheral blood mononuclear cells (PBMCs) was assessed in four cases before and after BMT. HTLV-I proviral DNA load was reduced significantly after transplantation. Unrelated BMT is feasible for treatment of ATLL. Further studies in a larger number of cases are required to determine the optimal conditioning regimen and stem cell source.

Sonochemically enhanced adsorption and degradation of methyl orange with activated aluminas.

Removal of Methyl orange (MO), as a model contaminants, in aqueous solution by the simultaneous application of ultrasound with the addition of porous adsorbent powders is reported. Activated alumina powders in acidic form were used as an adsorbent. Results showed that MO could be degraded by ultrasonic irradiation at 130 kHz with the first order rate constant of 8x10(-4) and 5x10(-4) sec(-1), in acidic and basic conditions, respectively, without adsorbents. Adsorption rates of MO by activated alumina mainly depended on the acidity of alumina, the pH of solution and the stirring speed. At pH=4.2 with mechanical stirring without ultrasonic radiation, acidic activated alumina (0.1 g/100 ml) removed MO at about two times more rapidly than ultrasonic irradiation. In the case of simultaneous application of ultrasound irradiation and activated alumina, MO was almost removed from the solution within 10 min, which corresponded to as a rate constant of 5x10(-3) sec(-1). This kind of synergistic enhancement of removal rate with ultrasound and adsorbents should be practically useful for the elimination of contaminants in the water treatment processes. In addition, the effects of pH and coexisting chemicals in the solution were examined for the processes. Although the adsorption process was effective in some selected conditions, ultrasonic degradation was more robust in wider range of pH and coexisting chemicals. Simultaneous application of the two processes can perform complementary.

Plasma stromal cell-derived factor-1 during granulocyte colony-stimulating factor-induced peripheral blood stem cell mobilization.

In this report, we examined plasma stromal cell-derived factor-1 levels in normal healthy donors for allogeneic peripheral blood stem cell transplantation (PBSCT) and in patients for autologous PBSCT using an enzyme-linked immunosorbent assay. The average level of plasma stromal cell-derived factor-1 was 2197 pg/ml before granulocyte colony-stimulating factor administration and 1899 pg/ml on day 4, demonstrating a significant decrease in the peripheral blood of healthy donors (P=0.0003). In patients for autologous PBSCT, a significant decrease of plasma stromal cell-derived factor-1 in the peripheral blood was also observed (P=0.0464). However, the physiologic gradient of stromal cell-derived factor-1 between peripheral blood and bone marrow was never inverted in normal healthy donors or in autologous PBSCT patients. Our results suggest that stromal cell-derived factor-1 may not be involved in the granulocyte colony-stimulating factor-induced release of CD34(+) cells to the peripheral blood. Further studies of a possible additive effect of granulocyte colony-stimulating factor and stromal cell-derived factor-1 are warranted.

Cytomegalovirus enteritis after autologous peripheral blood stem cell transplantation.

A 61-year-old male with non-Hodgkin's lymphoma (peripheral T-cell lymphoma, unspecified, clinical stage IVb) received autologous peripheral blood stem cell transplantation (PBSCT) during first remission. He was seropositive for cytomegalovirus (CMV) prior to autologous PBSCT. His posttransplant clinical course was complicated by refractory CMV enteritis, which manifested persistent abdominal pain, diarrhea, and bloody stool. Generally, gastrointestinal CMV disease is relatively rare after autologous PBSCT. However, our case indicates that CMV infection must be considered as a differential diagnosis in cases of unexplained hemorrhagic enteritis following autologous PBSCT.

Risk factors for massive hemoptysis after endobronchial brachytherapy in patients with tracheobronchial malignancies.

BACKGROUND: Massive and mostly fatal hemoptysis is a frequently reported morbidity after endobronchial brachytherapy (EBB) for tracheobronchial malignancies. However, to the authors' knowledge, it remains controversial whether this morbidity is related directly to EBB. To investigate whether massive hemoptysis is related to EBB, the authors retrospectively analyzed risk factors for massive hemoptysis after EBB. METHODS: Thirty-six patients (30 men and 6 women) with a mean age of 70 years underwent high-dose rate EBB for tracheobronchial malignancy using a cobolt-60 (Co-60) afterloading machine. EBB was performed as primary therapy in 6 patients and as salvage treatment for recurrent disease in 30 patients. EBB was delivered to the tracheal lesions in 15 patients and to the main bronchial lesions in 21 patients. EBB was combined with external beam radiation therapy (EBRT) in 24 patients, with laser photocoagulation in 3 patients, and with EBRT plus laser photocoagulation in 5 patients. The dose of EBRT delivered with the EBB ranged from 16-69 grays (Gy), with a mean dose of 37 Gy. RESULTS: At a mean follow-up of 18 months, 33 of the 36 patients had died. Eight of the 33 patients had no evidence of local disease at the time of death. Seven patients died of massive hemoptysis. The cumulative rate of massive hemoptysis was 29.4% at 2 years. According to univariate analysis, no statistically significant correlation with massive hemoptysis was observed for EBRT dose delivered in combination with EBB, EBB fractional and total doses, EBB length, and the sum of all the EBRT doses including that used for the initial treatment. Local failure or persistent malignancy (P = 0.033) and delivery of laser photocoagulation (P = 0.032) were found to be statistically significantly associated with massive hemoptysis. Direct contact between the EBB applicator and the tracheobronchial walls at the vicinity of the great vessels was observed in 16 patients and was found to be statistically significantly associated with massive hemoptysis (P = 0.003). In six patients, the applicator was in direct contact with two or more tracheobronchial walls at the vicinity of the great vessels; all these patients died of massive hemoptysis. CONCLUSIONS: Direct contact between the EBB applicator and the tracheobronchial walls at the vicinity of the great vessels was one of the significant risk factors for massive hemoptysis. To prevent massive hemoptysis, a specific spacer should be employed to maintain a safe distance between the applicator and the bronchial wall.

Quantification of ground-glass opacity on high-resolution CT of small peripheral adenocarcinoma of the lung: pathologic and prognostic implications.

OBJECTIVE: The purpose of our study was to correlate the high-resolution CT findings of small peripheral adenocarcinoma of the lung with underlying histopathology and to evaluate the prognostic implications of the CT findings. MATERIALS AND METHODS: The high-resolution CT findings of small peripheral adenocarcinoma of the lung in 224 patients were analyzed by two independent observers for location, size, marginal characteristics, and extent of ground-glass opacity and necrosis. The pathologic specimens were reviewed by an experienced lung pathologist. RESULTS: One hundred and thirty-two patients had bronchioloalveolar carcinoma and 92 had adenocarcinoma. The extent of ground-glass opacity was greater in bronchioloalveolar carcinomas (mean +/- SD, 29% +/- 31.6%) than in other adenocarcinomas (8% +/- 13.3%) (p < 0.001). The extent of ground-glass opacity was significantly greater in patients without recurrence (p = 0.020) and those without nodal (p = 0.017) or distant (p = 0.007) metastases than in patients with nodal or distant metastases or in whom the carcinoma had recurred. CONCLUSION: The extent of ground-glass opacity in a nodule is greater in bronchioloalveolar carcinomas than in other adenocarcinomas. Greater extent of ground-glass opacity also correlates with improved prognosis.

Pulmonary involvement in primary Sjögren's syndrome: spectrum of pulmonary abnormalities and computed tomography findings in 60 patients.

The purpose of this study was to describe the high-resolution computed tomography (HRCT) findings of pulmonary involvement in primary Sjögren's syndrome. The study included 60 patients who met the diagnostic criteria for primary Sjögren's syndrome. The authors retrospectively reviewed the presence, extent, and distribution of various HRCT findings. Results showed that the most common HRCT findings were areas with ground-glass attenuation (92%), followed by subpleural small nodules (78%), non-septal linear opacity (75%), interlobular septal thickening (55%), bronchiectasis (38%), and cysts (30%).

Pitfalls in the interpretation of multidetector-row helical CT images at window width and level setting for lung parenchyma.

This article describes pitfalls in the interpretation of multidetector-row helical CT (MDCT) images at the window width and level settings for lung parenchyma. On MDCT, linear artifacts, which look like black and white linear densities and are called "hurricane artifacts," radiate out from objects that have very different densities from their neighbors. For the evaluation of fine parenchymal details, a low table speed/slice collimation should be used. In fact, axial (step and shoot) scanning may be more effective for the evaluation of fine details. Since artifacts from vessels highly enhanced by contrast medium cause data blackout in the surrounding areas at high table speed/slice collimation, pulmonary parenchyma in such situations should be evaluated with unenhanced CT. Although multidetector-row helical CT is a promising tool for the evaluation of lung parenchyma, it is important to identify its shortcomings due to artifacts when interpreting images at the window width and level settings for lung parenchyma and to apply the appropriate methods for eliminating such artifacts.

High-resolution CT using multidetector CT equipment: evaluation of image quality in 11 cadaveric lungs and a phantom.

OBJECTIVE: The aim of this study was to evaluate the image quality and diagnostic efficacy of multidetector high-resolution CT (HRCT) by comparing it with single-detector HRCT and by comparing the noise and artifact of multidetector HRCT images with a phantom. SUBJECTS AND METHODS: Multidetector HRCT with six parameters and single-detector HRCT were performed on cadaveric lungs. The image quality and diagnostic efficacy of multidetector HRCT were evaluated in comparison with those of single-detector HRCT. A phantom was scanned, and image artifact and noise were investigated. RESULTS: . The image quality of multidetector HRCT with axial 1.25 mm x 4i (four images per gantry rotation) mode was equal to that of single-detector HRCT. The image quality of multidetector HRCT with other modes was worse than that on single-detector HRCT. The diagnostic efficacy of multidetector HRCT with high-quality mode (pitch, 3:1) and axial mode was equal to that of single-detector HRCT. The diagnostic efficacy on multidetector HRCT with high-speed mode (pitch, 6:1) was worse than that on single-detector HRCT. In the phantom study, images made in high-speed mode had strong artifacts. Noise in the axial mode was milder than that in high-speed mode but more severe than that in high-quality mode. CONCLUSION: The image quality of axial HRCT with multidetector CT is equal to that on single-detector HRCT. Axial HRCT with multidetector CT is appropriate for evaluating subtle lung abnormalities, but high-speed mode is unsuitable. Using the high-quality mode degrades image quality but is still worthwhile.

Plantar verrucous carcinoma: report of a case treated with Boyd amputation followed by reconstruction with a free forearm flap.

Verrucous carcinoma is a relatively rare, well-differentiated, squamous cell carcinoma. Although it is slow-growing and mimics benign skin lesions, it can cause extensive local destruction that necessitates amputation. It is often underdiagnosed as a benign tumor in its early course. We report a case of extensive verrucous carcinoma on a recalcitrant ulcer and a severe long-standing scar around it on the sole of the right forefoot, which had been treated as a benign tumor for more than two years. We treated it successfully with amputation of the foot and were able to spare the heel by using a free innervated forearm flap to cover the defect at the stump. The present case should remind clinicians that a verrucous lesion developing on a refractory ulcer may be a complex malignant neoplasm; an accurate diagnosis is difficult without a combination of clinical features and pathological findings from an adequately deep specimen.

Molecular characterization of the ERGIC-53 gene in two Japanese patients with combined factor V-factor VIII deficiency.

Combined deficiency of factor V and factor VIII is a distinct clinical entity and is an autosomal recessive disorder. Recently identification of the gene, the endoplasmic reticulum-Golgi intermediate compartment (ERGIC-53), responsible for combined factor V-factor VIII deficiency and mutations of the ERGIC-53 gene in affected patients have been reported. In this report we analyzed two Japanese patients with combined factor V-factor VIII deficiency by genomic polymerase chain reaction and sequencing analysis. In one patient we found a point mutation of C to T at nucleotide 604 in exon 5, resulting in a transition of arginine to stop codon, which was reported in previous reports. The DdeI digestion study demonstrated that this patient is homozygous for this nonsense mutation. In the other patient we found no mutation in the ERGIC-53 gene in analysis of the entire coding region and the intron/exon junctions, which is also consistent with the previous reports, suggesting the possibility of defects at other genetic loci.

Invasive and noninvasive thymoma: distinctive CT features.

PURPOSE: The purpose of this work was to evaluate the CT features of thymoma and to determine the most helpful findings in differentiating invasive from noninvasive thymoma. METHOD: The CT scans from 27 patients with invasive thymoma and 23 with noninvasive thymoma were independently assessed by two observers without knowledge of their invasiveness. The presence and distribution of various CT findings were independently analyzed. RESULTS: Invasive thymomas were more likely to have lobulated (16/27, 59%) or irregular (6/27, 22%) contours than noninvasive thymomas (8/23, 35% and 1.5/23, 6%, respectively) (p < 0.05). Invasive thymomas had a higher prevalence of low attenuation areas within the tumor (16/27, 60%) than noninvasive thymomas (5/23, 22%) (p < 0.001) as well as foci of calcification (14.5/27, 54% vs. 6/23, 26%; p < 0.01). CONCLUSION: The presence of lobulated or irregular contour, areas of low attenuation, and multifocal calcification is suggestive of invasive thymoma.

The performance of general-purpose colour CRT monitors in PACS environment.

General-purpose colour cathode ray tube (CRT) monitors are used commonly for image display in personal computer-based picture archiving and communication system (PACS) and telemedicine systems. At present, however, we have not enough information about their performance or reliability for this task. Therefore, we studied the performance of five general-purpose colour CRTs and the changes in their performance in a year. Resolution was measured visually using original digital images. Maximum and minimum luminances were measured at the centre and periphery of the CRTs. Distortion was measured in the centre and periphery using original digital images. All the monitors met their specifications. The inhomogeneity of luminance exceeded 20% and varied across the CRTs. Darker monitors took more time to reach stable luminance levels. The corner brightness seemed to be a good estimator of both performance and distortion in colour monitors.

Dependence of sonoluminescence intensity on the geometrical configuration of a reactor cell.

Dependence of sonoluminescence (SL) intensity on the geometrical configuration of a reactor cell is studied theoretically and experimentally. The model is a rectangular glass cell set in a water-cooling bath. Ultrasound is irradiated from the bottom of bath into the cell. Theoretical analysis of transmitted acoustic energy assuming a plane acoustic wave clarified the influences of distance between the transducer and the cell bottom, thickness of the cell bottom, and water depth in the cell. The theory is examined through intensity measurement of SL emitted in the cell using a photomultiplier tube. Dependence of SL intensity on the above parameters agreed with the theory very well. Distributions of SL are also observed using a high sensitive CCD camera and are compared with optically visualized sound fields to show the relationship between the sound field and the SL.

Expression of Epstein-Barr virus in cutaneous T-cell lymphoma including mycosis fungoides.

Cutaneous T-Cell lymphoma (CTCL) is a non-Hodgkin's lymphoma of unknown pathogenesis. Mycosis fungoides (MF) is a clinically determined subset of CTCL with intensive infiltration of lymphoma cells into the epidermis. To determine whether Epstein-Barr virus (EBV) is associated with these lymphoma cells, we performed mRNA in situ hybridization in 5 cases of CTCL and 7 cases of MF using an RNA probe transcribed from BamHI W fragment of EBV genome. These transcripts were detected in the majority of lymphoma cells in all cases examined. We also detected intensive hybridization signals on epidermal squamous cells contiguous to strong infiltration with lymphoma cells into the subcutaneous connective tissue. Similarly, positive signals were detected using the probes transcribed from the sequences of EBV-encoded small nonpolyadenylated RNAs-1 (EBER1) and EBV-determined nuclear antigen-2 (EBNA2). The EBNA2 latent membrane protein-1 (LMP1) and BZLF1 product (ZEBRA) were also detected by immunofluorescence staining using monoclonal antibodies. Further in the same experiment, we detected immunofluorescence of epidermal cells. EBV DNA was detected in all cases tested by DNA in situ hybridization. Moreover, we also identified the signals on epidermal cells via this technique. Polymerase chain reaction revealed amplified EBV DNA for most cases tested. Double staining with immunohistochemistry and RNA in situ hybridization showed that T-cell marker-positive cells, but not EBV-carrying B-cells, exhibited signals for the EB viral RNA. These findings suggest that EBV is involved in the neoplastic transformation of CTCL and MF.

Pulmonary involvement in mixed connective tissue disease: high-resolution CT findings in 41 patients.

The objective of this study was to describe the pulmonary abnormalities on high-resolution computed tomography (CT) in patients with mixed connective tissue disease (MCTD). The study included 41 patients who met the diagnostic criteria for MCTD and showed abnormal findings on high-resolution CT. The presence, extent, and distribution of various high-resolution CT findings were evaluated. The predominant abnormalities included areas of ground-glass attenuation (n = 41), subpleural micronodules (n = 40), and nonseptal linear opacities (n = 32). Other common findings included peripheral predominance (n = 40), lower lobe predominance (n = 39), intralobular reticular opacities (n = 25), architectural distortion (n = 20), and traction bronchiectasis (n = 18). Less common findings included honeycombing, ill-defined centrilobular nodules, airspace consolidation, interlobular septal thickening, thickening of bronchovascular bundles, bronchial wall thickening, bronchiectasis, and emphysema. Pulmonary involvement of MCTD is characterized by the presence of ground-glass attenuation, nonseptal linear opacities, and peripheral and lower lobe predominance. Ill-defined centrilobular opacities were uncommonly seen.