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INTRODUCTION Congenital fibrinogen disorders (CFDs) are caused by mutations in fibrinogen-encoding genes, FGA, FGB, and FGG, which lead to quantitative or qualitative abnormalities of fibrinogen. Although the diagnosis of CFDs is based on antigenic and functional level of fibrinogen, few genotypes are clearly correlated with phenotype. METHODS In this study, we investigated all of the referred patients diagnosed as CFDs in Taiwan's population between 1995 and 2020. Clinical features, laboratory data and genetic defects were analysed. Functional fibrinogen level was determined by the Clauss method. Antigenic fibrinogen was measured by an enzyme-linked immunosorbent assay. Fibrinogen genes were assessed for mutations by polymerase chain reaction and sequencing. RESULTS A total of 18 patients from six unrelated families with CFDs were identified. One patient from a consanguineous family was diagnosed as afibrinogenemia type 1A with a novel homozygous frameshift mutation in FGB exon 4. The other five (83.3 %) index patients were all diagnosed as dysfibrinogenemia type 3A caused by two novel and one known mutation. Six (33.3 %) patients from three families had a novel mutation in FGB exon 8. The clinical features and laboratory data were highly variable among these patients with the same mutation. CONCLUSIONS Three novel mutations of CFDs causing afibrinogenemia and dysfibrinogenemia were identified. The point mutation in FGB exon 8 is also a common mutation in Taiwan's population. Considerable phenotypic variability among the patients with an identical mutation was observed.

Time to Make a Change in the Cutoff Value of Clarithromycin Resistance in the Treatment of Helicobacter pylori Infection

Proton pump inhibitor (PPI)-amoxicillin-fluoroquinolone triple therapy is recommended as a second-line treatment of Helicobacter pylori infection in the Maastricht V/Florence Consensus Report. However, the eradication rate of this standard salvage treatment is suboptimal. The objective of this study is to compare the efficacy of esomeprazole-bismuth-tetracycline-levofloxacin therapy (TL quadruple therapy) and esomeprazole-amoxicillin-levofloxacin triple therapy (AL triple therapy) in rescue treatment for H. pylori infection.Consecutive H. pylori-infected subjects after failure of first-line therapies were randomly allocated to receive either TL quadruple therapy (esomeprazole 40 mg b.d., bismuth 120 mg q.d.s., tetracycline 500 mg q.d.s., and levofloxacin 500 mg o.d.) or AL triple therapy (esomeprazole 40 mg b.d., amoxicillin 500 mg q.d.s., and levofloxacin 500 mg o.d.) for 10 days. H. pylori status was assessed 6 weeks after the end of treatment.The study was stopped after an interim analysis. Of 50 patients in the TL quadruple therapy, 49 (98.0%) had successful eradication of H. pylori infection. Cure of H. pylori infection was achieved in 36 of 52 patients (69.2%) receiving AL triple therapy. Intention-to-treat analysis demonstrated that TL quadruple therapy achieved a markedly higher eradication rate than AL triple therapy (difference: 28.8%; 95% confidence interval: 15.7% to 41.9%; P0.001). Per-protocol analysis yielded a similar result (97.8% vs. 68.6%; P0.001). The two treatment groups exhibited comparable frequencies of overall adverse events (22.0% vs. 11.5%) and drug compliance (90.0% vs. 98.1%). The subgroup analysis showed that TL quadruple therapy was superior to AL triple therapy in patients with failure of either standard triple therapy (100% vs. 75.0%; P=0.010) or non-bismuth quadruple therapy (95.0% vs. 52.6%; P=0.003).Ten-day PPI-bismuth-tetracycline-levofloxacin quadruple therapy is a good option for rescue treatment of H. pylori infection following failure of standard triple or non-bismuth quadruple therapy.

In this paper, an innovative architecture for realizing a dual-mode retrodirective array (RDA) is proposed and experimentally validated. The new design functions as a reflection-type RDA in one frequency band and features the characteristics of a Van Atta array in the other band. A unique 50-Ω synthesized microstrip line is applied to fulfill the core building blocks of this RDA, i.e., the dual-mode quadrature hybrids and crossovers. Both couplers show equivalent responses to their conventional counterparts in the low-frequency band, but enable direct-thru transmission properties in the high band. To validate this innovative architecture, a four-element dual-mode RDA is fabricated and experimentally verified. The measured bistatic radiation patterns provide supportive evidence to the dual-band self-steering capability of the proposed array. The circuit topologies, design approaches, system considerations, and simulated and measured results are investigated in detail throughout this paper. Suggestions to improve the system performance are discussed as well.

We present a modified quasi-Yagi antenna for use in WLAN access points. The antenna uses a new microstrip-to-coplanar strip (CPS) transition, consisting of a tapered microstrip input, T-junction, conventional 50-ohm microstrip line, and three artificial transmission line (ATL) sections. The design concept, mode conversion scheme, and simulated and experimental S-parameters of the transition are discussed first. It features a compact size, and a 3dB-insertion loss bandwidth of 78.6%. Based on the transition, a modified quasi-Yagi antenna is demonstrated. In addition to the new transition, the antenna consists of a CPS feed line, a meandered dipole, and a parasitic element. The meandered dipole can substantially increase to the front-to-back ratio of the antenna without sacrificing the operating bandwidth. The parasitic element is placed in close proximity to the driven element to improve impedance bandwidth and radiation characteristics. The antenna exhibits excellent end-fire radiation with a front-to-back ratio of greater than 15 dB. It features a moderate gain around 4 dBi, and a fractional bandwidth of 38.3%. We carefully investigate the concept, methodology, and experimental results of the proposed antenna.

A new integrated feeding network for dual-band retrodirective array (RDA) is discussed in this paper. The core building block is the dual-mode synthesized transmission line. Without applying active switches, the synthesized line makes the array feeding network identical to a reflection-type RDA in one band, but resemble a phase conjugating array (PCA) in the other band. With the phase conjugating array involved, modulated data can be injected into the network to fulfill information transmission between the interrogator and the RDA. A four-element dual-band retrodirective array is fabricated to experimentally validate the concept with bistatic radiation patterns.

From 1986 to 1998, 26 (23%) of 114 adult acute lymphoblastic leukemia (ALL) patients and 11 (4%) of 328 pediatric patients were found to have Philadelphia (Ph) chromosome. In the 30 patients with available data at diagnosis, 18 (60%) had extra-chromosomal abnormalities. They included 1q duplication (5/18, 28%), supernumerary Ph chromosome (4/18, 22%), 9p abnormalities (3/18, 17%), 7q deletion/monosomy 7 (3/18, 17%), trisomy 19 (1/18, 6%), and trisomy 8 (1/18, 6%). Excluding those with specific cytogenetic changes, only one patient had hyperdiploid karyotype with more than 50 chromosomes. The incidence of 1q duplication was higher and that of hyperdiploidy was lower in this study than has been previously reported. There was no prognostic implication of these additional cytogenetic abnormalities. With fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR), 14 (27%) of 53 unselected adult ALL patients and 2 (5%) of 38 unselected pediatric patients were BCR-ABL-positive, including one adult and two children without Ph chromosome. The BCR-ABL fusion genes/transcripts were also present in all other 16 selected Ph-positive ALL patients. The BCR-ABL fusion subtypes were determined in all these 32 patients: 91% (11/12) childhood cases showed m-type fusion gene while 45% (9/20) adult ones did so (P = 0.0083). The clinical outcome was similar between the two groups of patients with m-type and M-type BCR-ABL. In conclusion, both cytogenetic and molecular studies are very helpful for identifying the subgroup of ALL patients with Ph/BCR-ABL. The additional cytogenetic abnormalities and subtypes of BCR-ABL fusion genes/transcripts had no significant implications in this group of patients.

From January 1986 to December 1998, 26 (23%) of 114 acute lymphoblastic leukemia (ALL) patients older than 15 years were found to have Philadelphia (Ph) chromosome. They accounted for 28% (26 of 94) of the patients with B-lineage ALL. Compared with the other 88 ALL patients, the leukemic cells from all but one Ph-positive ALL patients were early pre-B cells with a higher rate of CD34 expression (92% vs 50%, P0.05). At presentation, the Ph-positive adult ALL patients had higher circulating blasts (mean 21.4 vs 3.66x10(4)/microl, P0.05) and lower initial platelet counts (mean 4.47 vs 7.34x10(4)/microl, P0.01) and showed a trend toward higher frequency of initial central nerve system (CNS) involvement (25% vs 11%, P=0.098) than the others. Among patients with adequate chemotherapy, 16 (64%) of the 25 Ph-positive ALL patients achieved complete remission (CR), an incidence marginally lower than that of Ph-negative ALL (62 of 76, 82%, P=0.06) and significantly lower than that of Ph-negative B-lineage ALL (50 of 58, 86%, P=0.0037). However, all patients relapsed except for those who received allogeneic hemopoietic stem cell transplantation (allo-HSCT). The probabilities of 5-year continuous CR and 5-year survival for Ph-positive adult ALL patients were significantly inferior to those for Ph-negative adult ALL patients (0% vs 12%, P=0.0001, and 7% vs 19%, P=0.047, respectively), and those for Ph-negative B-lineage ALL (0% vs 14%, P0.0001, and 7% vs 23%, P=0.002, respectively). Prognostic factors were analyzed among the Ph-positive ALL patients including the 26 adults mentioned above and an additional 11 children. No clinical or biological characteristics such as age, sex, initial circulating blast count, extramedullary involvement, or CD34 expression had an impact on the disease outcome. Allo-HSCT in first CR may improve the probability of 5-year continuous CR (100% vs. 0% for those without allo-HSCT, P=0.0091) although only three patients received it in this study. In conclusion, Ph-positive ALL patients tended to have a poor prognosis, regardless of whether other possible risk factors were present or not. Aggressive treatment, such as high-dose chemotherapy with allo-HSCT, should be considered for these patients to improve survival.

Background. Gastroesophageal reflux disease (GERD) may present with gastroesophageal and extraesophageal symptoms. Currently, the frequencies of gastroesophageal and extragastroesophageal symptoms in Asian patients with different categories of GERD remain unclear.Aim. To investigate the frequencies of gastroesophageal and extragastroesophageal symptoms in patients with mild erosive esophagitis, severe erosive esophagitis, and Barrett’s esophagus of GERD.Methods. The symptoms of symptomatic subjects with (1) Los Angeles grade A/B erosive esophagitis, (2) Los Angeles grade C/D erosive esophagitis, and (3) Barrett’s esophagus proven by endoscopy were prospectively assessed by a standard questionnaire for gastroesophageal and extragastroesophageal symptoms. The frequencies of the symptoms were compared by Chi-square test.Result. Six hundred and twenty-five patients (LA grade A/B: 534 patients; LA grade C/D: 37 patients; Barrett’s esophagus: 54 patients) were assessed for gastroesophageal and extragastroesophageal symptoms. Patients with Los Angeles grade A/B erosive esophagitis had higher frequencies of symptoms including epigastric pain, epigastric fullness, dysphagia, and throat cleaning than patients with Los Angeles grade C/D erosive esophagitis. Patients with Los Angeles grade A/B erosive esophagitis also had higher frequencies of symptoms including acid regurgitation, epigastric acidity, regurgitation of food, nausea, vomiting, epigastric fullness, dysphagia, foreign body sensation of throat, throat cleaning, and cough than patients with Barrett’s esophagus.Conclusion. The frequencies of some esophageal and extraesophageal symptoms in patients with Los Angeles grade A/B erosive esophagitis were higher than those in patients with Los Angeles grade C/D erosive esophagitis and Barrett’s esophagus. The causes of different symptom profiles in different categories of GERD patients merit further investigations.

This paper gives a brief summary of the design concept of the so-called “dual-mode” synthesized transmission lines with their applications to novel antenna arrays. The dual-mode synthesized line, by definition, is a miniaturized, nonperiodic basic building block capable of providing distinct circuit responses in different frequency bands of interest. The design methodology will be introduced briefly, followed by two application examples including the dual-mode retrodirective array and dual-band decoupling network. Prospective applications are discussed at the end of the paper.

By utilizing a pair of quasi-lumped LC tanks, in this paper, a new 50-ohm synthesized microstrip line is proposed. Differing from its conventional counterparts, the new design shows open-circuit input impedance at its attenuation pole, which isolates the synthesized line from other transmission paths. A compact dual-mode four-port network, having quadrature-coupling and direct-thru transmission properties in each of the two frequency bands, is developed based on this new synthesized line. This novel four-port network behaves like a conventional 3-dB quadrature hybrid in the low frequency band, but can be equivalent to a pair of isolated transmission lines in the high band. In addition, it is 50% the size of a conventional design. The design methodology, circuit layouts, and experimental results of the synthesized line and the dual-mode four-port network are discussed carefully in this paper.

A compact multilayered three-channel multiplexer is investigated in this paper. The multiplexer is developed by integration of ten synthesized microstrip lines and striplines. It has three transmission passbands at 0.9, 1.8, and 2.4 GHz. Open-circuited stubs are utilized as wave trapping circuits to provide port isolation. A new idea for synthesizing high-impedance artificial line is discussed. The proposed multiplexer shows a compact size of 14.5 × 12.5 mm2. The circuit configuration and simulated and experimental results are discussed.

A number of articles have investigated the outcomes of total knee arthroplasty (TKA) and causes of prosthetic failure in patients with haemophilic arthropathy. The aims of this retrospective study were to evaluate the clinical and functional outcomes of TKA and causes of prosthetic failure in patients with haemophilic arthropathy. A consecutive series of 35 TKA in 26 patients with haemophilic arthropathy were performed between November 1985 and October 2006 by one experienced surgeon. The mean age at index operation was 34.2 years old (range: 23.4-47 years) and the mean follow-up duration was 82.2 months (range: 12-218 months). Clinical assessment included range of flexion, range of extension and total range of motion (ROM). Functional evaluation comprised pain score and functional score by Dr. Insall's Knee Society Clinical Rating System. The average preoperative ROM was 63.2 degrees with flexion contracture 15 degrees , whereas the average postoperative ROM was 79.8 degrees with flexion contracture 5.5 degrees . Improvement of range of flexion was 7.1 degrees (P = 0.16); improvement of range of extension was 9.5 degrees (P < 0.01). Average increase of total ROM was 16.6 degrees (P = 0.02). Pain score by Knee Society was 7.1 points preoperatively and 48 points postoperatively (P < 0.01); functional score by Knee Society was 42 points preoperatively and 77.1 points postoperatively (P < 0.01). Three patients received manipulations because of an inadequate ROM. Three infection episodes were treated with debridement and one of them received arthrodesis after removal of prosthesis. Two patients received revision TKA. One of them was because of loosening of femoral component. The other one received revision TKA because of insert wear. Though improvement in range of flexion is insignificant in haemophilic arthropathy of knee after TKA, it showed significant increase in total ROM after operation, especially in improvement of flexion contracture. It also showed great pain relief and significant functional gain. Under the circumstance of acceptable infection rate and complication, TKA is an effective method to achieve pain relief and gain better function in patients with haemophilic arthropathy of knee. The data of this study confirm those previously published by many authors.

Transformation of myelodysplastic syndrome to hematologic malignancies is not uncommon, but involvement of three committed progenitor cell lines at one time is seldom seen. We present a case of myelodysplastic syndrome with blast transformation, neoplastic cells that were difficult to classify morphologically, and basophilia found in marrow and peripheral blood. Differential diagnosis included myeloblastic leukemia, erythroblastic leukemia, megakaryoblastic leukemia, basophiloblastic leukemia, and systemic mast cell disease (SMCD). By using a battery of cytochemical techniques niques and irnrnuno~tochemicalm ethods, we were able to demonstrate the presence of myeloblasts, erythroblasts, and megakaryoblasts, thus excluding the possibility of SMCD and basophiloblastic leukemia. (The J Histotechnol 13:67, 1990)

The microbiological spectrum in cancer patients with febrile neutropenia has changed over the past several decades in western countries. The growing incidence of antimicrobial resistance is an inevitable consequence of the widespread use of antibiotics in medical settings. The aim of this study was to clarify the trends and antimicrobial resistance among pathogens causing bloodstream infections in febrile neutropenic adults with hematological malignancies.The characteristics of pathogens causing bloodstream infection isolated from patients with febrile neutropenia who were treated at National Taiwan University Hospital from 1996 to 2001 were reviewed. A total of 1174 pathogens were isolated from 3093 admissions to a hematological ward during this period. Among them, 738 isolates were recovered from patients with febrile neutropenia.The majority (93%) of these neutropenic febrile patients had underlying acute leukemia or lymphoma. Gram-negative bacteria accounted for 57% of isolated pathogens, followed by Gram-positive bacteria (32%), fungi (7%), and anaerobes (3%). In decreasing frequency, Escherichia coli (13%), Klebsiella pneumoniae (12%), Enterobacter cloacae (7%), Pseudomonas aeruginosa (6%), and Acinetobacter baumannii (5%) were the predominant Gram-negative bacteria, while coagulase-negative staphylococci (13%), viridans group streptococci (4%), and Staphylococcus aureus (4%) were the major Gram-positive pathogens. Two-thirds (20/30) of S. aureus isolates were resistant to oxacillin. No vancomycin-resistant enterococci were isolated. Resistance to cefotaxime was found in 63% of E. cloacae, 13% of K. pneumoniae and 10% of E. coli. Overall, 33% of E. coli and 13% of K. pneumoniae were resistant to ciprofloxacin.This study indicates that the microbiological spectrum of microorganisms causing bloodstream infections in neutropenic febrile patients with hematological malignancies at National Taiwan University Hospital is different from western countries in that Gram-negative bacteria remain the predominant pathogens. Antimicrobial resistance among these pathogens is high and E. coli and K. pneumoniae isolates with resistance to third-generation cephalosporins and ciprofloxacin are increasing.

Fifty Taiwanese patients with relapsed and/or refractory multiple myeloma (MM) were treated with thalidomide on a dose-escalation schedule, commencing with 100 mg/d nightly and incremented either to the maximally tolerated dose or 800 mg/d. Twenty-two patients (44%) responded, with 10 (45.5%) classified as partial remission and 12 (54.5%) minimal response (MR). Complete response did not occur. Of the 28 non-responders, 14 were progressive disease and 14 stable. The median time from commencement of thalidomide treatment to initial achievement of MR was 29 days (range, 8~155), and the corresponding thalidomide dose was 200 mg/d (range, 100~500). The median tolerated dose of thalidomide for the entire sample was 400 mg/d (range, 100~800), with only two (4%) able to tolerate 800 mg/d. Comparing responsive and non-responsive patients, statistically significant differences were not demonstrated for any characteristics except for CRP level and percentage cytogenetic change, which was slightly higher in the latter group relative to the former. Of particular interest, 18 of the 22 responders experienced transient reduction of leukocyte count preceding the attainment of significant reduction in M-proteins in comparison to only four of the 28 non-responders (82% vs. 14%; p0.001). The median time from commencement of thalidomide treatment to attainment of minimal leukocyte count was 28 days (range, 7~150), with a mean of 2.19x10(9)/l (range, 0.96~3.35x10(9)/l). Leukopenia was generally transient, with rapid recovery despite subsequent continuation of thalidomide. Levels of other non-hematologically adverse effects attributed solely to thalidomide were generally acceptable. For 25 patients, thalidomide treatment was supplemented with low-dose dexamethasone (4 mg, every other day). Of these, 11 had relapsed from and 14 were primarily refractory to thalidomide treatment. Nine of the 25 dexamethasone-supplemented patients were responders (36%). Of particular note were the unusual events noted with this thalidomide-dexamethasone combination, including vascular thrombosis, acute cholecystitis, idiopathic interstitial lung disease and sudden cardiac death. Our results suggest that thalidomide is also effective for Taiwanese patients with refractory and/or relapsed MM. Importantly, the transient reduction in leukocyte count after commencement of thalidomide treatment may serve as a clinical predictor for response. Adverse effects should be carefully monitored when combining thalidomide and dexamethasone, however.

Nosocomial fungal infection increases gradually and has become the leading pathogen at National Taiwan University Hospital since 1993. From January 1995 through May 2002, hepatosplenic fungal infection (HSF) was diagnosed in 37 (7.4%) of the 500 adult patients with acute leukemia who received chemotherapy at this hospital. There was no significant difference in the incidence of HSF between the patients with acute myeloid leukemia and those with acute lymphoblastic leukemia, or between the patients treated with high-dose chemotherapy and those with conventional or low-dose chemotherapy. Candida tropicalis was the leading pathogen, followed by Candida albicans. The computed tomography scan showed multiple hypodense lesions in the liver (89%), spleen (70%), and kidney (27%). Eighteen patients were initially treated with fluconazole and 19 with amphotericin B. Nineteen patients received the planned chemotherapy after the diagnosis of HSF. Among them, eight patients underwent hematopoietic stem cell transplantation and seven patients survived more than 100 days post-transplantation; none of these patients had relapse of prior HSF. Twenty-three patients (62%) died during a median follow up of 10 months, but only seven died due to HSF. In conclusion, a substantial percentage of patients with acute leukemia acquired HSF after chemotherapy and carried high mortality. However, HSF itself is not a contraindication for subsequent chemotherapy and hematopoietic stem cell transplantation.

Abstract 1564 Poster Board I-587 Somatic mutation of AML1/RUNX1 (RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 individuals (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male gender, older age, lower LDH value, FAB M0/M1 subtypes and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19 and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD (P=0.0061), but negatively associated with CEBPA (P=0.0057) and NPM1 mutations (P=0.0001). AML patients with RUNX1 mutations had a significantly lower complete remission rate, shorter disease-free and overall survival than those without the mutation (P=0.0087, P Disclosures No relevant conflicts of interest to declare.