Search

Purpose To investigate the long-term progression of pericentral hydroxychloroquine retinopathy. Design Multicenter, retrospective cohort study. Participants Eighty eyes (60 with pericentral pattern) of 41 Korean patients with hydroxychloroquine retinopathy followed up for 2 years or more after drug cessation. Methods Patients were screened for hydroxychloroquine retinopathy using spectral-domain or swept-source OCT, fundus autofluorescence (FAF), and Humphrey visual field (VF) tests. Follow-up was divided into short-term (≤2 years) and subsequent periods, and progression was evaluated in each period and severity group. Retinopathy progression on OCT was defined as increased length of the ellipsoid zone defect, decreased distance from the fovea to the photoreceptor defects, or newly developed or enlarged retinal pigment epithelium defects. On FAF, progression was defined as an increase in the area of hyperautofluorescence or hypoautofluorescence. Functional progression was defined as a regression coefficient of less than 0 dB/year for mean deviation and more than 0 dB/year for pattern standard deviation, based on linear regression analysis of 3 or more VF tests. Structural and functional progression rates were calculated using the slopes of retinal thicknesses on the Early Treatment Diabetic Retinopathy Study grid and perimetric parameters over time, respectively. Main Outcome Measures Structural and functional progression of retinopathy. Results Approximately one third of eyes with early pericentral retinopathy showed limited progression during the short-term period after drug cessation, but they subsequently showed stable or improved photoreceptors. Most eyes with moderate pericentral retinopathy showed continuous progression, particularly when converted to the severe stage. Severe eyes showed progressive damage throughout the follow-up period. In all severity groups, the rates of retinal thinning decreased over time. In eyes with pericentral retinopathy showing progression, circumferential enlargement of retinal damage was prominent in earlier stages, whereas centripetal enlargement of the ring-shaped lesion was noted in advanced stages. Functional progression, noted in 58.7% of the pericentral eyes, corresponded with structural progression. Conclusions Pericentral hydroxychloroquine retinopathy showed severity-dependent progression. Moderate pericentral retinopathy usually progressed, but centripetal progression threatening the fovea was remarkable mostly in severe retinopathy. Our results suggest that early detection of retinopathy may minimize the risk of progression to foveal involvement in pericentral retinopathy.

Herein, we introduce the infusion direction manipulation technique and the infusion off technique. These relatively simple methods control intra-vitreal fluid flow direction and turbulence and release negative pressure in the microforceps to facilitate handling of the internal limiting membrane. The aim of this study is to introduce an effective and uncomplicated method to handle the internal limiting membrane (ILM) during the temporal inverted ILM flap and free ILM flap techniques in macular hole surgery by controlling the direction and status of the infusion.The direction of the infusion flow was controlled with a free finger (usually the 4th finger) during the inverted ILM flap surgery to stabilize the flap location during the fluid-air exchange. A valved trocar was used, and the infusion was discontinued during the free ILM flap surgery. Turbulence was minimized, and negative pressure around the head-shaft junction of the microforceps was released.The ILM flap remained stable in all patients who underwent macular hole surgery with our technique.Infusion direction manipulation technique and infusion off technique are efficient and simple methods to handle the ILM during ILM surgery.

The most important requirements of biomedical substitutes used in muscle tissue regeneration are appropriate topographical cues and bioactive components for the induction of myogenic differentiation/maturation. Here, we developed an electric field-assisted 3D cell-printing process to fabricate cell-laden fibers with a cell-alignment cue. Methods: We used gelatin methacryloyl (GelMA) laden with C2C12 cells. The cells in the GelMA fiber were exposed to electrical stimulation, which induced cell alignment. Various cellular activities, such as cell viability, cell guidance, and proliferation/myogenic differentiation of the microfibrous cells in GelMA, were investigated in response to parameters (applied electric fields, viscosity of the bioink, and encapsulated cell density). In addition, a cell-laden fibrous bundle mimicking the structure of the perimysium was designed using gelatin hydrogel in conjunction with a 4D bioprinting technique. Results: Cell-laden microfibers were fabricated using optimized process parameters (electric field intensity = 0.8 kV cm-1, applying time = 12 s, and cell number = 15 × 106 cells mL-1). The cell alignment induced by the electric field promoted significantly greater myotube formation, formation of highly ordered myotubes, and enhanced maturation, compared to the normally printed cell-laden structure. The shape change mechanism that involved the swelling properties and folding abilities of gelatin was successfully evaluated, and we bundled the GelMA microfibers using a 4D-conceptualized gelatin film. Conclusion: The C2C12-laden GelMA structure demonstrated effective myotube formation/maturation in response to stimulation with an electric field. Based on these results, we propose that our cell-laden fibrous bundles can be employed as in vitro drug testing models for obtaining insights into the various myogenic responses.

BACKGROUND AND PURPOSE The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (

Background The measure of processes of care (MPOC) is a widely used instrument to assess parents' perception of the extent to which healthcare services they and their child receive are family centred. The purpose of this study was to examine the reliability and validity of the Korean translation of the MPOC (Korean MPOC). Methods The Korean MPOC was completed by 198 parents of children receiving rehabilitation services in five provinces in South Korea. According to the Canadian validation procedures, analyses for internal consistency, construct and concurrent validity, and test-retest reliability were performed. Results The Korean MPOC demonstrated adequate internal consistency, with Cronbach's alpha ranging from .85 to .98. Confirmative analyses of the scale structure support the construct validity of the Korean MPOC. The Pearson correlations r between the MPOC scale scores and Client Satisfaction Inventory score ranged from .60 to .83, supporting the concurrent validity of the Korean MPOC. The intraclass correlation coefficients were greater than .80 for all five scales, demonstrating good test-retest reliability. Conclusions The Korean MPOC has good psychological properties and can be recommended for evaluation of processes of paediatric rehabilitation in Korea.

Objectives To determine the potential for immunodiagnostic application of two recombinant forms of Clonorchis sinensis omega-class glutathione transferases (rCsGSTo1 and rCsGSTo2) against human small liver-fluke C. sinensis and Opisthorchis viverrini infections. Methods Specific antibody levels against rCsGSTo1 and rCsGSTo2 in patients' sera of egg-positive opisthorchiasis ( n = 87) and clonorchiasis ( n = 120), as well as those in sera from patients with other helminthic infections ( n = 252) and healthy controls ( n = 40) were retrospectively analysed by ELISA. Results We observed highly positive correlation coefficients between specific antibody levels against rCsGSTo1 and rCsGSTo2 and egg counts per gramme of faeces (EPG) of patients with opisthorchiasis ( n = 87; r = 0.88 for rCsGSTo1 and r = 0.90 for rCsGSTo2). Sera from opisthorchiasis patients whose EPG counts >100 ( n = 43) revealed high antibody titres against both antigens. Patients' sera with low EPG counts ( n = 44) also exhibited reliable sensitivities of 93.2% and 97.7% for rCsGSTo1 and rCsGSTo2, respectively. Sera from clonorchiasis patients showed sensitivities of 90% (108/120 samples) and 89.2% (107/120 sera) for rCsGSTo1 and rCsGSTo2. Overall diagnostic sensitivities for liver-fluke infections were 92.3% for rCsGSTo1 (191/207 samples) and 93.2% for rCsGSTo2 (193/207 samples). Specificities were 89.7% (rCsGSTo1) and 97.6% (rCsGSTo2). Conclusions Detection of specific antibody levels against rCsGSTo1 or rCsGSTo2 might be promising for the serodiagnosis of patients infected with these two phylogenetically close carcinogenic liver-flukes.

Acute GVHD (aGVHD) is an important risk factor for predicting the incidence or severity of chronic GVHD (cGVHD). Transplant outcome can be influenced by the onset time of aGVHD in patients who have received allogeneic PBSC transplants (PBSCTs). The medical records of 134 patients who survived more than 3 months after myeloablative allogeneic PBSCT were retrospectively reviewed. In all, 38 patients (28.4%) developed grade II-IV aGVHD before day +28 (early aGVHD) and 25 patients (18.7%) after day +28 (late aGVHD). The 5-year cumulative incidence of cGVHD was 78.9% in the early-aGVHD group and 56.6% in the late-aGVHD group (P=0.034). The 5-year OS was 51.0% for the early-aGVHD and 80.8% for the late-aGVHD group (P=0.406). Infection was the primary cause of death for the early-aGVHD group (51.4 vs 16.7%, P=0.017), whereas relapse of the primary disease was higher among the patients with late aGVHD, although this was statistically insignificant (58.3 vs 25.7%, P=0.309). In a multivariate analysis, early aGVHD was identified as a risk factor for developing cGVHD (hazard ratio (HR) 2.278, P=0.004). The development of aGVHD early after allogeneic PBSCT increased the risk of cGVHD and infection-related death rate when compared with the late onset of aGVHD.

An evidence-based (EB) approach has been a significant driver in reforming healthcare over the past two decades. This change has extended across a broad range of health professions, including oral healthcare. A key element in achieving an EB approach to oral healthcare is educating our practitioners, both current and future. This involves providing opportunities integrated within simulated and actual clinical settings for practitioners to learn and apply the principles and processes of evidence-based oral healthcare (EBOHC). Therefore, the focus of this discussion will be on ways in which EBOHC and associated research activities can be implemented into curricula, with the aim of improving patient care. This paper will initially define the scope of EBOHC and research, what these involve, why they are important, and issues that we need to manage when implementing EBOHC. This will be followed by a discussion of factors that enable successful implementation of EBOHC and research into curricula. The paper concludes with suggestions on the future of EBOHC and research in curricula.Key recommendations related to curricula include strengthening of the culture of a scientific approach to education and oral healthcare provision; complete integration of EBOHC into the curriculum at all levels; and faculty development to implement EBOHC based on their needs and evidence of effective approaches. Key recommendations to support implementation and maintenance of EBOHC include recognition and funding for high-quality systematic reviews and development of associated methodologies relevant for global environments; building global capacity of EBOHC researchers; research into improving translation of effective interventions into education and healthcare practice, including patient-reported outcomes, safety and harms, understanding and incorporation of patient values into EB decision-making, economic evaluation research specific to oral healthcare and effective methods for changing practitioner (faculty) behaviours; and extend access to synthesized research in 'user friendly' formats and languages tailored to meet users' needs. Realizing these recommendations may help to improve access to effective healthcare as a basic human right.

Helicobacter pylori associated gastric cancer arises via a multistage process, with atrophic gastritis being the precursor lesion. Helicobacter pylori is typically acquired in childhood, yet little is known of the prevalence of atrophic gastritis in childhood.To study atrophic gastritis among children from countries with high gastric cancer incidence.Sections from topographically mapped gastric biopsy specimens from children undergoing clinically indicated endoscopy in Korea and Colombia were evaluated using visual analogue scales. Atrophy was defined as loss of normal glandular components, including replacement with fibrosis, intestinal metaplasia (IM), and/or pseudopyloric metaplasia of the corpus (identified by the presence of pepsinogen I in mucosa that was topographically corpus but phenotypically antrum).One hundred and seventy three children, 58 from Korea (median age, 14 years) and 115 from Colombia (median age, 13 years), were studied. Helicobacter pylori was present in 85% of Colombian children versus 17% of Korean children (p0.01). Atrophic mucosa near the antrum-corpus border was present in 16% of children, primarily as pseudopyloric metaplasia (31%, IM; 63%, pseudopyloric metaplasia; 6%, both). The median age of children with corpus atrophy was 15 (range, 7-17) years.Gastric atrophy occurs in H pylori infected children living in countries with high gastric cancer incidence. Identification and characterisation of the natural history of H pylori gastritis requires targeted biopsies to include the lesser and greater curve of the corpus, starting just proximal to the anatomical antrum-corpus junction, in addition to biopsies targeting the antrum and cardia.

Thrombocytopenia (TP) is a frequent complication after allogeneic stem cell transplantation (SCT) and regarded as a poor prognostic factor when assessed beyond day 100. However, little is known about the clinical significance of the platelet recovery pattern before chronic graft-versus-host disease (GVHD) develops. Eighty-five patients undergoing HLA-identical sibling SCT were stratified according to their platelet recovery pattern between day +30 and +90 and the transplant outcomes analyzed, along with the association of each component of the acute GVHD grading system. Fifteen patients (18%) were classified with persistent TP, 33 patients (39%) with unstable TP, and 37 patients (43%) as non-TP. Persistent TP, which was strongly associated with severe acute GVHD (P

Few studies have addressed the incidence of graft-versus-host disease (GVHD) or survival after ABO-incompatible allogeneic peripheral blood stem cell transplantation (PBSCT). We analyzed the clinical outcome of ABO incompatibility after allogeneic PBSCT. A total of 89 consecutive adult patients with hematological diseases including 49 ABO-identical, 20 major, 15 minor, and five bidirectional ABO-incompatible transplants were enrolled from four medical centers in Korea. No significant difference in engraftment times, graft failure, or transfusion requirements between groups was noted. A clinical diagnosis of severe immune hemolysis or pure red cell aplasia was not made for any patient after transplantation. The incidence of acute or chronic GVHD did not statistically differ between groups. With a median follow-up duration of 13 months (range, 0.5-61 months), the 3-year overall survival estimates for the ABO-identical, major/bidirectional, and minor group were 44.6.0+/-9.0, 43.1+/-11.6, and 43.8+/-13.5%, respectively (P=0.8652), while the 3-year disease-free survival estimates were 33.8+/-7.6, 39.9+/-11.4, and 45.7+/-13.1%, respectively (P=0.8546). We observed that time to neutrophil, platelet, and red blood cell engraftment, transfusion requirements, incidence of acute or chronic GVHD, relapse, and survival were not influenced by ABO incompatibility after allogeneic PBSCT from HLA-matched sibling donors.

Hickman catheter site infections are known to increase transplant-related mortality. A retrospective analysis of 103 patients who received allogeneic stems cell transplants was performed to define the incidence and outcomes of Hickman infections. Seventy-six patients received peripheral blood stem cells (PBSC) (73.8%) and 29 patients (28.2%) nonmyeloablative conditioning. During the median follow-up of 9 months, Hickman infections were observed in 10 patients (9.7%) at a median onset of 32 days posttransplant (range 2 to 102 days). The causative organisms identified in five cases included Staphylococcus species (n = 4) and Pseudomonas aeruginosa (n = 1). Six events successfully resolved with antibiotic treatment, while the other four required the removal of the Hickman catheter with subsequent death in two cases. The survival duration for infected patients was shorter than that for the noninfected group (83 days vs 366 days, P < .001). Myeloid engraftment was delayed in the infected group (18.0 days vs 15.0 days, P = .038) and this complication was more frequently observed among the BMT compared with PBSC group (22.2% vs 5.3%, P = .019). Hickman infections were associated with transplant-related mortality especially during the first 3 months posttransplant. As such, the current results emphasize both the importance of Hickman catheter care and the need for surveillance cultures after stem cell transplantation.

Reharvesting leukocytes from donors for a donor leukocyte infusion (DLI) is inconvenient and occasionally impossible in case of unrelated donors. It is well known that the effect of a growth factor-primed DLI is comparable to that of a nonprimed DLI. In total, 42 patients with hematologic malignancies and a high risk of relapse were allocated, on an intent-to-treat basis, a peripheral blood stem cell transplantation (PBSCT) from HLA-matched sibling donors, and then at the time of harvest, additional peripheral blood stem cells (PBSCs) were also reserved for a therapeutic primed DLI in case of relapse. In all, 12 patients who relapsed after allogeneic PBSCT were treated with mainly cytarabine-based chemotherapy followed by a cryopreserved PBSC infusion. The median dose of CD3+ and CD34+ cells for the primed DLIs was 1.43 x 10(8)/kg and 4.75 x 10(6)/kg, respectively. Six of the 12 relapsed patients exhibited a complete response after the primed DLI, plus their 1-year survival rate was 33%. The new development or progression of graft-versus-host disease after a primed DLI was observed in 50% of the patients. Overall, the survival at 1 year was 16.7%. Accordingly, the induction of a graft-versus-leukemia effect through a primed DLI, using additional PBSCs reserved at the original time of harvest, would appear to be feasible for patients with relapsed hematologic malignancies. Furthermore, this approach is also more convenient for donors.

It is important to optimize methods to mobilize hematopoietic stem cells into peripheral blood (PB) for successful allogeneic peripheral blood stem cell (PBSC) transplantation. Our primary intent was to investigate the role of GM-CSF for mobilization in normal healthy donors and to compare its efficacy in mobilizing stem cells alone, in concurrent combination and in sequential combination with G-CSF in this study. We analyzed the results of the PBSC harvest through large volume leukapheresis from 48 normal healthy donors mobilized by three different regimens including GM-CSF. Donors were assigned sequentially to one of the following regimens for mobilization: GM-CSF 10 microg/kg/day alone (group 1, n = 9); concurrent combination (group 2, n = 20) of G-CSF 5 microg/kg/day and GM-CSF 5 microg/kg/day; sequential combination (group 3, n = 19) of GM-CSF alone 10 microg/kg/day for 3 days followed by G-CSF alone 10 microg/kg/day for 2-3 days. The harvested CD34(+) cell count (P0.05) was statistically higher in group 3 than in group 1 or 2. Pre-collection WBC count in donors (P0.05), harvested MNC (P0.05) and CD3(+) cell count (P0.05) of group 2 or 3 were significantly higher than those of group 1. Recipients who received stem cells mobilized with combination regimens showed an earlier recovery of WBC and platelets count than those with GM-CSF alone. The incidence of acute graft-versus-host disease was not statistically different among three recipient groups. GM-CSF-based mobilization was well tolerated in normal healthy donors. The sequential combination regimen appears to be an excellent mobilization strategy and might be preferred as the optimal method in some clinical situations that need a higher number of stem cells.

Objective: This study was conducted to evaluate the potential of a novel trifunctional methacrylate as a component of a photocurable composite resin with reduced curing shrinkage. Methods: Tris[4-(2′-hydroxy-3′-methacryloyloxypropoxy)phenyl]methane (TTEMA) was synthesized by reacting triphenylolmethane triglycidyl ether (TTE) with methacrylic acid in the presence of 4-(dimethylamino)pyridine. Photopolymerization reactivity and volumetric shrinkage of unfilled resins based on TTEMA were investigated by Fourier transform infrared spectroscopy and density measurements, respectively, and the results were compared with those for conventional dental monomers. A three-point bending test of the TTEMA-containing composite resin was carried out. Results: TTEMA was easily prepared in a good yield of 89%. Unfilled resins of TTEMA and bis-GMA, each containing 40% TEGDMA, showed similar photopolymerization reactivity. TTEMA exhibited a very low photopolymerization shrinkage of 2.09%, and 3:2 TTEMA–TEGDMA unfilled resin revealed 10% lower shrinkage than a conventional bis-GMA system containing the same amount of TEGDMA. The flexural strength of a light-activated composite resin formulated with TTEMA is comparable to that of a bis-GMA composite resin under the same conditions. Significance: TTEMA is promising for application as a photocurable dental monomer due to ease of synthesis, good polymerization reactivity, and relatively low curing shrinkage.

BACKGROUND Standard allogeneic bone marrow transplantation (BMT) offers only a small chance of cure for most adult patients with advanced hematologic malignancies. The authors postulated that allogeneic peripheral blood stem cell transplantation (PBSCT) followed by prophylactic growth factor-primed donor lymphocyte infusion (DLI) with cells reserved at harvest would maximize the graft-versus-tumor effects in patients with hematologic malignancies who had a high risk of recurrence. METHODS Seventeen patients with hematologic malignancies who had a high risk of recurrence were allocated on an intent-to-treat basis to allogeneic PBSCT from human leukocyte antigen-matched sibling donors followed by prophylactic growth factor-primed DLI of cells reserved at harvest for transplantation. RESULTS The median age was 37 years (range, 19–56 years). All donors underwent two or more apheresis procedures. The median numbers of mononuclear cells (MNCs), CD34 positive (CD34+) cells, and CD3+ cells, respectively, that were collected for 17 donors were 9.0 × 108 MNCs/kg (range, 4.9–14.4 × 108 MNCs/kg), 13.0 × 106 CD34+ cells/kg (range, 2.4–75.2 × 106 CD34+ cells/kg), and 5.8 × 108 CD3+ cells/kg (range, 3.3–9.9 × 108 CD3+ cells/kg) for a mean number of 2.35 apheresis procedures (range, 2.0–4.0 procedures). The median numbers of MNCs and CD3+ cells that were cryopreserved were 2.1 × 108 MNCs/kg (range, 0.0–4.4 × 108 MNCs/kg) and 1.4 × 108 CD3+ cells/kg (range, 0.0–3.5 × 108 CD3+ cells/kg). Seven of 17 patients received additional PBSCs, with a median of 5.0 × 107 CD3+ cells/kg (range, 3.0–9.9 CD3+ cells/kg) between Day 41 and Day 120. The reasons for inability to administer additional PBSCs in 10 patients included early death (n = 4 patients), severe graft-versus-host disease (GVHD) (n = 3 patients), disease recurrence (n = 2 patients), and harvest failure (n = 1 patient). Of seven patients, two patients died of recurrence, and one died of cytomegalovirus pneumonitis. The surviving four patients were free of disease when last assessed (median follow-up, 597 days) but were suffering from chronic GVHD (one patient had limited GVHD, and three patients had extensive GVHD). CONCLUSIONS The authors suggest that allogeneic PBSCT with prophylactic growth factor-primed DLI may be a potentially curative strategy for the treatment of hematologic malignancies in patients with a high risk of recurrence. Their approach may offer the additional advantage of collecting enough cells at harvest for the potential use of DLI, which is easy, convenient for donors, and cost effective. Cancer 2002;94:18–24. © 2002 American Cancer Society.

The aim of this study was to present a systematic sequence for three-dimensional (3D) measurement and cephalometry, provide the norm data for computed tomography-based 3D architectural and structural cephalometric analysis, and validate the 3D data through comparison with Delaire's two-dimensional (2D) lateral cephalometric data for the same Korean adults. 2D and 3D cephalometric analyses were performed for 27 healthy subjects and the measurements of both analyses were then individually and comparatively analyzed. Essential diagnostic tools for 3D cephalometry with modified definitions of the points, planes, and measurements were set up based on a review of the conceptual differences between two and three dimensions. Some 2D and 3D analysis results were similar, though significant differences were found with regard to craniofacial angle (C1-F1), incisal axis angles, cranial base length (C2), and cranial height (C3). The discrepancy in C2 and C3 appeared to be directly related to the magnification of 2D cephalometric images. Considering measurement discrepancies between 2D and 3D Delaire's analyses due to differences in concept and design, 3D architectural and structural analysis needs to be conducted based on norms and a sound 3D basis for the sake of its accurate application and widespread adoption.

OBJECTIVE: The purpose of this study was to evaluate the CT features of intraperitoneal manifestations with parasitic infestation in nine patients. CONCLUSION: The CT features of intraperitoneal manifestations of parasitic infestation were single or multiple multiseptated cystic masses in the peritoneal cavity, hazy omental infiltration, or both. Recognizing these features is important to establish an early diagnosis that leads to rapid treatment and helps avoid unnecessary surgery.

Human leukocyte antigen (HLA)-G is an immune modulator that inhibits the functions of cytotoxic T lymphocytes and natural killer cells. Immune modulation of HLA-G plays an important role in the prevention of fetal rejection. We found a novel substitution at nucleotide position 195 (G-T), codon 41 (Ala), in exon 2 of HLA-G. This substitution does not change the amino acid (GCG-->GCT).

Bone loss is recognized as worsening the quality of life in long-term survivors of Allo-SCT. This study evaluated the risk factors associated with bone loss and the role of zoledronic acid in preventing bone loss in allogeneic recipients. Fifty-three patients who underwent HLA-matched Allo-SCT were evaluated for their bone mineral density (BMD) in the lumbar spine and femoral neck at regular intervals. Zoledronic acid (4 mg) was given i.v. to 18 patients (ZA patients) at 2 months after SCT and then every 3 months until 2 years. Grade 2-4 acute GVHD was associated with bone loss (odds ratio (OR)=4.90, 95% confidence interval (CI)=1.41-16.99; P=0.012) at 1 year after SCT, whereas extensive chronic GVHD and steroid use were both unfavorable prognostic factors (OR=9.00 and 7.22, 95% CI=1.52-53.40 and 1.44-36.22; P=0.016, respectively) in terms of osteopenia/osteoporosis at 2 years after transplantation. The use of zoledronic acid significantly prevented bone loss in the femoral neck as well as the spine (OR=0.18, 95% CI=0.05-0.69, P=0.012). Therefore, BMD measurements and the use of zoledronic acid are recommended in cases of GVHD or long-term steroid use after Allo-SCT to prevent bone loss and threatening skeletal events.

A regimen of busulfan and cyclophosphamide (BuCy2) is regarded as the standard myeloablative regimen for SCT. This study evaluated the hypothesis that fludarabine can replace cyclophosphamide for myeloablative allogeneic SCT. Ninety-five patients underwent allogeneic SCT from HLA-identical donors, following BuCy2 (n=55) or busulfan+fludarabine (BF, n=40). The efficacy of fludarabine compared to cyclophosphamide was retrospectively evaluated. The BF group exhibited a shorter duration until engraftment (P=0.001), lower incidence of acute and chronic GVHD (P

This study attempts to identify variables that can predict the development of progressive- or quiescent-type chronic GVHD (pq cGVHD) and transplant outcomes after the diagnosis of cGVHD in 99 patients who experienced acute GVHD (aGVHD) after allogeneic SCT. The prognostic significance of various clinical parameters at diagnosis of cGVHD was examined to determine the prognostic factors for GVHD-specific survival (GSS) in patients with pq cGVHD. Among 118 patients who experienced any degree of aGVHD, 99 were evaluated for cGVHD. The incidence of overall and extensive pq cGVHD at 2 years was estimated as 84.4 and 63.1%, respectively. A multivariate analysis showed that severe aGVHD (grade 3, 4) (P=0.022), primary treatment failure (P=0.009) and elevated alkaline phosphatase (P=0.001) were all significant independent factors predicting a higher overall incidence of pq cGVHD. The GSS and probability of systemic immunosuppressive treatment at 2 years after diagnosis of cGVHD were estimated as 55.9 and 51.9%. GVHD-specific survival was significantly associated with performance status (P=0.004) and lymphocytopenia (or=1000/microl, P=0.022) at diagnosis of cGVHD by Cox's proportional hazard model. Severe aGVHD, primary treatment failure (PTF), lymphocytopenia and elevated alkaline phosphatase may be useful predictive factors for the development of pq cGVHD in patients who experience aGVHD after allogeneic SCT.

To compare H2-receptor antagonists and proton pump inhibitors as adjuvants to triple therapy for Helicobacter pylori eradication.H. pylori-infected patients with peptic ulcer were randomized to receive either 300 mg nizatidine or 30 mg lansoprazole plus 1 g amoxicillin and 500 mg clarithromycin taken b.d. for 7 days. H. pylori eradication was assessed 4 weeks after therapy. Using meta-analytical techniques, we combined the results of this study with other randomized controlled comparisons of H2-receptor antagonists and proton pump inhibitors as adjuvants to triple therapy.One hundred and one patients were randomized. H. pylori eradication was 94% (47/50) [95% confidence interval (CI), 83-99%] (intention-to-treat) in the H2-receptor antagonist group vs. 86% (44/51) (95% CI, 74-94%) in the proton pump inhibitor group (P = 0.3). There has been a total of 12 similar studies (1415 patients). The overall efficacy was similar in intention-to-treat analysis: 78% (549/701) with H2-receptor antagonists vs. 81% (575/714) with proton pump inhibitors (odds ratio, 0.86; 95% CI, 0.66-1.12). A non-significant trend favouring H2-receptor antagonist (79% vs. 69%; odds ratio, 1.14; 95% CI, 0.76-1.71; P = 0.5) was seen in the comparison of clarithromycin-containing regimens. In contrast, in non-clarithromycin-containing trials, there was a slight, but significant, advantage with proton pump inhibitors (85% vs. 78%; odds ratio, 0.64; 95% CI, 0.45-0.92; P = 0.02).Overall, proton pump inhibitor and H2-receptor antagonist antisecretory agents appear to be similarly effective as adjuvants for H. pylori triple therapy. It is unlikely that the direct anti-H. pylori effect of proton pump inhibitors is responsible for their ability to enhance anti-H. pylori therapy.

Production of cytokines along with increased activity of nitric oxide synthase has been implicated as one of the contributing mechanisms of Helicobacter pylori-mediated gastroduodenal diseases. We aimed to evaluate the effect of rebamipide in treating Helicobacter pylori-associated duodenal ulcers in terms of cytokine production and nitrosative damage of the gastric mucosa. In patients with duodenal ulcers, rebamipide or placebo were given randomly after eradication. Mucosal cytokine production was measured by enzyme linked immunoassay, and nitrotyrosine immunoexpression was measured by immunohistochemistry. The inflammatory activity and degree of neutrophil infiltration were graded accordingly. The mucosal production of RANTES, interleukin-8, and TNF-alpha showed a significant decrease after eradication in patients with rebamipide after-treatment. The nitrotyrosine immunoreactivity of gastric epithelium was significantly decreased in the rebamipide group. Rebamipide treatment after eradication resulted in a significant reduction in chemokine production along with nitrotyrosine immunoexpression in Helicobacter pylori-associated duodenal ulcers.

Genomic research has identified a quantitative trait locus for uterine capacity, a component trait contributing to litter size, on porcine chromosome 8. The epidermal growth factor (EGF) gene, on porcine chromosome 8, may influence uterine capacity because of its growth-promoting activities. Using reverse transcription-polymerase chain reaction (PCR) and iterative screening of a porcine reproductive tissue cDNA library, 4932 bp cDNA sequence coding for porcine EGF precursor was obtained. The predicted protein sequence of the EGF precursor contained 1214 amino acids, similar to human EGF precursor (1207 amino acids, 81% identity). Curiously, the sequence of the mature peptide was less homologous between species than other regions of EGF precursor. The presence of conserved regions outside the mature peptide may suggest that these regions are functionally important. Expression of EGF mRNA in the endometrium of White crossbred gilts (n 5 3 to 5 each) was determined by Northern blotting using 20 mg of total RNA from endometrium of D 10, 13, and 15 cyclic, and D 10, 13, 15, 20, 30, and 40 of pregnant gilts. A 3342 bp probe from EGF precursor was used. The bands corresponding to EGF mRNA were quantified by densitometry and results were analyzed by ANOVA. EGF mRNA expression decreased significantly from D 13 to 15 of the cycle and pregnancy (P 5 0.04), and from D 30 to 40 of pregnancy (P 5 0.01). These findings show that EGF mRNA expression is temporally regulated during the cycle and early pregnancy, and this pattern of gene expression may be important during early conceptus development. © 2001 Elsevier Science

This study was carried out to reduce the possibility of high-order multiple gestations and the failure of embryo transfer by determining their replacement date based on the number and quality of 2-day embryos.All zygotes were cocultured with cumulus cells in 10 microliters of YS medium containing 10% human follicular fluid (hFF) for 48 or 96 hr. In period I, all embryos were transferred on day 3 (1032 cycles). In period II, the embryos were transferred on either day 3 or day 5 by determining their replacement date based on the number and quality of 2-day embryos: there were 2701 patients in whom embryos were replaced on day 3 (in the case that the number of zygotes was less than eight and the number of good-quality embryos was less than three) and 1952 patients less than 40 years old in whom embryos were replaced on day 5 (in the case that the number of zygotes was eight or more and/or the number of good-quality embryos was three or more). On the other hand, patients who were 40 years old or more were alloted to day 3 transfer cycles, regardless of the number and quality of the 2-day embryos, due to the possibility of their not producing blastocyst-stage embryos in vitro.The number of embryos transferred in period II was 2.9 +/- 0.6, while that in period I was 3.7 +/- 0.5. The multiple pregnancy rate was significantly decreased in period II (30.7%) compared to that (49.6%) in period I, while the pregnancy and implantation rates in period II (36.1 and 16.4%, respectively) were not lower than those (34.9 and 16.1%, respectively) in period I. The rate of triplet or more gestations was significantly minimized in period II (2.3%) compared to that in period I (26.5%).We propose that determination of the date on which embryos should be transferred based on the number and quality of embryos on day 2 may help to maintain an acceptable pregnancy rate, while minimizing embryo transfer failure and high-order multiple gestations.

Endothelial progenitor cells (EPCs) were recently demonstrated to exist in human cord blood. Phytohaemagglutinin (PHA), a potent mitogen for mononuclear cells was used to induce EPCs from unsorted cord blood mononuclear cells (CBMCs). Adherent cells in clusters appeared approximately 24 h after CBMCs were cultured in plain Roswell Park Memorial Institute media containing 10% fetal bovine serum (culture media) and PHA. Adherent cells were further propagated for 1 week in plain culture media. Flow cytometry and Di-I staining analyses showed that CD45-, CD34+, Flk-1+, CD31+ or VE-cadherin+ EPCs were induced and that they were mainly from the CD34+ cell compartment. When enriched CD34+ cells alone were stimulated with culture supernatant of the PHA-activated CBMCs, they neither proliferated readily nor induced EPCs. Because EPCs first appeared within the clustering cells that expressed high levels of fibronectin and vascular endothelial growth factor (VEGF), our data suggest that both cell-cell/cell-matrix interaction and the local VEGF action are important in the induction of EPCs. Thus, we demonstrate for the first time that EPCs are induced from human cord blood stem cell populations that interact with neighbouring PHA-activated CBMCs. This finding may have a significant implication in inflammatory cell-mediated vasculogenesis and angiogenesis in vivo.

The pathogenesis of uterine leiomyomata is still unclear. Recently it has been suggested that mac25 plays a tumor-suppressive role in various tumors. The aims of this study were to evaluate a possible involvement of mac25 in the growth of leiomyoma and in the mechanism of a gonadotropin-releasing hormone agonist (GnRHa) inducing shrinkage of leiomyoma.Mac25 mRNA transcript was measured by Northern blot in total RNA extracted from the paired specimens of leiomyoma and adjacent myometrium from untreated patients (n = 25) and from leiomyoma specimens from GnRHa-pretreated patients (n = 10).Mac25 mRNA expression was significantly lower in large leiomyoma (more than 150 cm3 in volume) than in adjacent myometrium and small leiomyoma (less than 120 cm3 in volume) from untreated patients. There was no difference in this expression between the proliferative and secretory phases of the menstrual cycle. Leiomyoma from GnRHa-pretreated patients had mac25 gene expression levels similar to myometrium and small leiomyoma from untreated patients.Mac25 may be involved in the growth of uterine leiomyoma and the action of GnRHa may, in part, be mediated by mac25.

The changes in circulating IGF components after the menopause and the potential role of new markers of bone turnover and circulating IGF components in predicting bone mass in postmenopausal women are still controversial and the relationship between these two systems has not been investigated. The aims of this study were to investigate the changes in circulating IGF components after the menopause, to evaluate whether new markers of bone turnover and circulating IGF components reflect bone mass in postmenopausal women under the age of 60 and to study the relationship between these two systems.Serum IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, osteocalcin (OST), bone specific alkaline phosphatase (BAP), urinary deoxypyridinoline (DPYD) and N-telopeptide of type I collagen (NTX) were measured in 31 premenopausal women aged 31-43 and 65 postmenopausal women aged 47-60: this latter group comprised 30 normal healthy women and 35 osteoporotic women.Compared with premenopausal women or normal postmenopausal women, serum IGF-1 and IGFBP-3 levels were significantly lower in osteoporotic postmenopausal women while no significant differences in serum levels of IGF-II, IGFBP-1 and IGFBP-2 were observed. The correlations between bone turnover markers and circulating IGF components (except between serum BAP and IGF-II), and between bone turnover markers and bone mineral density (BMD) in postmenopausal women were not significant. However, serum IGF-I and IGFBP-3 correlated positively with BMD of the lumbar spine and/or Ward's triangle even if age, BMI and menopause duration were taken into account in a multiple regression analysis model.Circulating IGF-I and IGFBP-3 may be involved in the mechanism of bone loss in postmenopausal women under the age of 60. They may also provide indirect information on the current bone microenvironment different from that provided by new markers of bone turnover.

Although the clinical efficacy of paclitaxel in the treatment of gastric carcinoma has not been clearly defined, recent reports have suggested a possible role in the treatment of upper gastrointestinal carcinomas in vitro and in vivo. In this study, the authors evaluated the efficacy and toxicity of a combination chemotherapy that included paclitaxel, 5-fluorouracil (5-FU), and cisplatin in the treatment of patients with advanced gastric carcinoma.Forty-one gastric carcinoma patients with metastatic disease, unresectable advanced disease, or relapsed disease were treated with the following regimen, administered every 28 days: paclitaxel 175 mg/m2 by 3-hour intravenous (i.v.) infusion on Day 1, 5-FU 750 mg/m2 by 24-hour continuous i.v. infusion on Days 1-5, and cisplatin 20 mg/m2 by 2-hour i.v. infusion on Days 1-5. Twenty-six patients had measurable disease, and 15 had evaluable disease. All patients were assessable for toxicity.Twenty-one of the 41 patients (51%; 95% confidence interval [CI], 36.5-65.7%) demonstrated an objective response, including 4 complete responses (10%; 95% CI, 3.9-22.5%). Sixty-five percent of the patients with measurable disease (17 of 26; 95% CI, 58-92.5%) and 27% of the patients with evaluable disease (4 of 15: 95% CI, 11.1-52.3%) achieved a complete response or a partial response. The median response duration was 17 weeks (range, 4-90 weeks), and the median survival duration for all patients was 26 weeks (range, 8 to 118+ weeks). The major toxicity of this treatment was myelosuppression with neutropenia of World Health Organization Grade 3 and 4 in 24% and 10% of the patients, respectively. Nonhematologic toxicity included mucositis, nausea/vomiting, diarrhea, neurotoxicity, and alopecia. Fluid retention occurred in two patients, and one patient had an anaphylatic reaction. Dose reduction was necessary for one patient, because Grade 4 neutropenia and mucositis occurred.Paclitaxel, 5-FU, and cisplatin was an active combination regimen in the treatment of advanced gastric carcinoma. The toxicity of this regimen was tolerable. Based on these findings, this combination regimen could be an attractive treatment in the preoperative setting.

A bee sting can cause a foreign body granuloma of the skin, due to activated macrophages at the stinging site. A 52-year-old woman presented with a large doughnut-shaped ulcerative tumour on the left side of her face. A bean-sized facial papule had grown to a 4.0 x 3.9 x 1.1 cm mass after multiple bee stings induced by herself over a period of 1 year. Histology showed epidermal ulceration with granulomatous inflammatory cell infiltration of many eosinophils. No micro-organisms or foreign bodies were identified. Intralesional triamcinolone acetonide was not effective, but an excellent outcome was obtained using carbon dioxide laser vaporization of the lesion.

It remains unclear why the spectrum of H. pylori-related diseases differs among different geographic regions. We examined the non-H. pylori contamination rates of the stomach in patients with duodenal ulcer or gastric adenocarcinoma from three different regions with different spectra of H. pylori-related diseases. Gastric biopsies were cultured from patients with duodenal ulcer or histologically proven gastric cancer from Seoul, Korea; Bogota, Colombia; and Houston, Texas. The frequency of non-H. pylori contamination was tallied in relation to the clinical diagnosis. Cultures from 247 duodenal ulcer patients and 165 patients with gastric cancer had bacterial growth. H. pylori was isolated from 207 (73.7%) patients with duodenal ulcer and 90 (47.1%) patients with gastric cancer (P0.001). In patients with duodenal ulcer (DU) or gastric cancer (GC), the rate of positive cultures for H. pylori were not statistically different (P0.143 for DU, P0.190 for GC) between regions. The frequency of isolation ranged from 69% to 79% for DU patients and from 39% to 50% for gastric cancer patients. Non-H. pylori bacterial contamination was found more frequently (63%) in Colombian duodenal ulcer patients compared to 30% ulcer patients from the United States or Korea (P0.001). Non-H. pylori growth occurred in 50.8-75.5% of cancer patients and was significantly lower in US patients than in patients from either Colombia or Korea (P0.01). The geographic location as well as disease status affects the rate of H. pylori recovery and non-H. pylori contamination of the stomach and may play a role in the geographic differences in manifestation of H. pylori infection. The fact that the proportion of gastric cancer patients in the United States with non-H. pylori contamination was significantly less than that of Korea or Colombia shows that the notion of an almost universal increase in gastric microbial content in gastric adenocarcinoma should be reconsidered.

Thirty-nine patients with locally advanced or metastatic gastric carcinoma received oral UFT (tegafur and uracil) plus leucovorin. Treatment consisted of UFT 360 mg/m2/day plus leucovorin 25 mg/m2/day, given orally in divided daily doses for 21 days followed by a 7-day rest period. The median age of the patients was 64 years, and the median World Health Organization performance status was 2. Patients received a median of two courses of treatment (range, 1 to 25). Among 37 evaluable patients, two patients achieved a complete response, and eight had partial responses, for an overall response rate of 27% (95% confidence interval, 15.4% to 42.9%). Stable disease was reported in 12 patients (32%) and another 15 showed disease progression. The median duration of response was 30 weeks, and the median duration of survival was also 30 weeks (range, 8 to 111). All patients were evaluable for toxicity. Significant toxicity (World Health Organization grade 3 or 4) included diarrhea in seven patients (18%), oral mucositis in six (15%), and nausea/vomiting in six patients. We conclude that oral UFT plus leucovorin, an outpatient regimen, has favorable activity in patients with gastric carcinoma and has tolerable toxicities.

A 12-year-old Korean girl gave a 9-year history of recurrent necrotizing papules and vesicles on the face, scalp and extremities. Skin biopsy specimens showed an atypical lymphoreticular infiltrate with vasculitis in the dermis and subcutis. In situ hybridization demonstrated latent infection by Epstein-Barr virus (EBV) of the lymphoid cells in the dermis. The disease was diagnosed as an EBV-associated lymphoproliferative skin eruption presenting as recurrent necrotic papulovesicles. The patient subsequently developed large granular lymphocytic leukaemia of natural killer cell origin. Our observations suggest that a patient with an EBV-associated lymphoproliferative skin eruption presenting with recurrent necrotic papulovesicles might progress to develop leukaemia as well as lymphoma.

The establishment and operation of the nervous system requires genetic regulation by a network of DNA-binding proteins, among which is the zinc finger superfamily of transcription factors. We have cloned and characterized a member of the unusual Cys-Cys-His-Cys (also referred to as Cys2HisCys, CCHC, or C2HC) class of zinc finger proteins in the developing nervous system. The novel gene, Myt1-like (Myt1l), is highly homologous to the original representative of this class, Myelin transcription factor 1 (Myt1) (Kim and Hudson, 1992). The MYT1 gene maps to human chromosome 20, while MYT1L maps to a region of human chromosome 2. Both zinc finger proteins are found in neurons at early stages of differentiation, with germinal zone cells displaying intense staining for MyT1. Unlike Myt1, Myt1l has not been detected in the glial lineage. Neurons that express Myt1l also express TuJ1, which marks neurons around the period of terminal mitosis. The Myt1l protein resides in distinct domains within the neuronal nucleus, analogous to the discrete pattern previously noted for Myt1 (Armstrong et al.: 14:303-321, 1995). The developmental expression and localization of these two multifingered CCHC proteins suggests that each may play a role in the development of neurons and oligodendroglia in the mammalian central nervous system.

Peritoneal macrophages are easily isolated by lavage, suggesting that they are either nonadherent or weakly adherent in situ. Cultured macrophages express class A scavenger receptors (SCR), which mediate Ca2+-independent adhesion in vitro. We examined fresh peritoneal macrophages from mice and from women with endometriosis to determine whether the adherence of these cells was associated with increased expression of class A SCR. Fresh human macrophages were not immunoreactive to SCR antibodies; however, SCR immunoreactivity increased with time in culture. Fresh mouse and human macrophages took up minimal amounts of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI)-acetyl-low density lipoproteins (Ac-LDL), a class A SCR ligand. Murine macrophages in culture for 24-72 h internalized four times more Ac-LDL than fresh cells. Cells cultured for 2 days incorporated 3.2 times more [14C] oleate than freshly isolated cells (55.7 +/- 7.9 versus 17.6 +/- 3.0 nmol/mg cell protein). In contrast to SCR activity, mouse macrophage SCR mRNA expression was similar in freshly isolated macrophages and those cultured for 3 days. These results suggest that peritoneal macrophages express only low levels of SCR activity in situ and that posttranscriptional regulation after isolation leads to an increase in SCR activity that correlates with adherence of the macrophages in vitro.

Background: Effective anti-Helicobacter pylori therapies with few side-effects are needed. We previously showed that the regimen of amoxycillin, clarithromycin and an H2-receptor antagonist was effective in the United States. The current study tested whether this therapy would also be successful in Korea. Methods: Patients with gastric or duodenal ulcers received amoxycillin (750 mg t.d.s.) plus clarithromycin (500 mg t.d.s.) for 2 weeks and nizatidine 300 mg at bedtime for 6 weeks. Endoscopic examinations were performed before treatment and 4 or more weeks after ending antimicrobial therapy. H. pylori status was confirmed by rapid urease testing and histological examination of gastric antrum and corpus biopsies using the Genta stain. Antibiotic resistance was tested using the E-test method. Cure was defined as no evidence of H. pylori infection 4 or more weeks after ending therapy. Results: Seventy-two patients (59 males and 13 females; mean age 46 years), including 35 with duodenal ulcers, 30 with gastric ulcers and seven with both, were studied. H. pylori infection was cured in 95.8% (69/72 patients; 95% CI = 88.3–99.1%). Two of the treatment failures had culture data and one had pre-treatment resistance to clarithromycin. Smoking did not have an adverse effect on therapy. Ten patients (15%) developed side-effects during treatment, but all were mild and did not require treatment interruption. No case of reinfection was noted during follow-up. Conclusion: The combination of amoxycillin, clarithromycin and an H2-receptor antagonist is effective in Korean patients with H. pylori infection.

Detection and characterization of distinct central nervous system (CNS) tumor cell types is clinically important since distinct tumor types are associated with different prognoses and treatments. However, there is currently a lack of markers to identify certain glioma types and insufficient understanding as to which cells give rise to different glioma cell types. In the present study, biopsy specimens from human brain tumors were analyzed for expression of Myelin Transcription Factor 1 (MYT1) to explore the extent to which glioma cells reflect characteristic expression of MYT1 in developing glial progenitor cells. Immunostaining with an antibody against MYT1 revealed widespread immunoreactivity that was most prominent in high-grade oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas as well as in a dysembryoplastic neuroepithelial tumor. MYT1 immunoreactivity in tumor regions generally correlated with the prevalence of cells exhibiting nuclear immunolabeling with an antibody against Ki-67, suggesting an association of MYT1 with cell proliferation that was also observed in normal adult human and rat brain in the germinal subependymal zone. The MYT1 immunoreactivity was frequently nuclear, appearing as dotted or punctate, but in some cases it was localized to the cytoplasm. In combination with histopathological studies and analysis of Ki-67 immunoreactivity, examination of MYT1 immunolabeling may provide additional information to aid in the detection and diagnosis of CNS tumors.

BACKGROUND & AIMS: Helicobacter pylori is not usually found in areas of intestinal metaplasia. Thus, the development of intestinal metaplasia has been viewed as a mechanism by which the stomach eliminates H. pylori. The aim of this study was to evaluate the frequency of H. pylori adherence to intestinal metaplasia in different populations. METHODS: Mapped gastric biopsy specimens from 378 H. pylori-positive subjects from various geographical regions were examined. Intestinal metaplasia was typed by staining with periodic acid-Schiff/alcian blue and high-iron diamine/alcian blue. RESULTS: In 32 patients, H. pylori was found in intimate contact with intestinal metaplasia. This was documented by electron microscopy. All areas of intestinal metaplasia showing adherence contained sulfomucins and had no brush border. Posttreatment biopsy specimens from 4 patients whose infection was not cured showed persistence of H. pylori in intestinal metaplasia. CONCLUSIONS: These patients may have a strain of H. pylori with unusual adhesion characteristics, or their type of intestinal metaplasia may have biochemical properties that make it hospitable for H. pylori. The exclusive association of H. pylori adherence with incomplete intestinal metaplasia (a putative precursor of carcinoma) and its greater frequency in Koreans (a population at risk for gastric cancer) suggest that this phenomenon may play a role in the hypothetical sequence metaplasia > dysplasia > carcinoma. (Gastroenterology 1996 Nov;111(5):1206-11)

Helicobacter pylori is an important factor in the development of duodenal ulcer disease and has been implicated in the pathogenesis of gastric adenocarcinoma. It has been suggested that the cagA gene is a marker for more virulent strains of H. pylori.We determined the prevalence of the cagA gene in 60 clinical isolates [34 from gastric carcinoma patients (CA), 26 from duodenal ulcer patients (DU)] from Korea, a country with a high incidence and mortality from gastric cancer. Genomic DNA was polymerase chain reaction-amplified by using two different primer sets for the cagA gene. The first cagA primer set amplifies a 297-bp product from the midregion of the cagA gene. The second primer set, which was previously established in a patient population from the Houston area (21 DU patients, 20 from individuals with asymptomatic gastritis) amplified a 1.4-kb region further downstream in the cagA gene.The expected 297 bp polymerase chain reaction amplicon for cagA was identified in 59/60 (98.3%) H. pylori isolates from Korea (33/34 CA, 26/26 DU), and in 36/41 (88%) isolates from the Houston area (20/21 DU, 16/20 asymptomatic gastritis) (NS). Using the second cagA primer set, the expected 1.4-kb product was found in only 1/60 (1.7%) H. pylori isolates from Korea (1/34 CA, 0/26 DU), and in 36/41 (88%) of isolates from the Houston area (20/21 DU, 16/20 GST) (p0.001). Western blot analysis showed that all Korean H. pylori isolates expressed cagA.The high prevalence of the cagA gene in H. pylori isolates from Korean patients with gastric adenocarcinoma or duodenal ulcers indicates that the cagA gene is common in H. pylori strains, and therefore, is not reliable as a single marker for the discrimination of H. pylori strains with respect to a specific disease. Our data further suggest that allelic variations in the genome of H. pylori strains may exist and that distinct H. pylori populations may circulate in different geographic regions.

A comparative study on inherited tooth morphology characters, in particular the incidence of Carabelli tubercles in the maxillary dentition, was conducted on standardized stone casts obtained from 240 Japanese (124 males (male) and 116 females (females)) and 160 Chinese (74 male, 86 female) young adults. The following results were obtained: 1) No significant differences in the incidence of Carabelli tubercles according to sex or body height were found between the two groups. 2) However, significant differences in the incidence of Carabelli tubercles according to sex were found in both groups. The tubercles occurred more frequently in males. 3) Significant differences between the bilateral and unilateral occurrence of Carabelli tubercles were observed in both the Japanese (p0.05) and Chinese (p0.01) groups; Carabelli tubercles on upper first molars were always bilateral. 4) The highest incidence of Carabelli tubercles was found in individuals with a body height of 166 approximately 175 cm in both groups, and a significant difference (p0.05) between the 156 approximately 165 cm and 166 approximately 175 cm groups was particularly evident in the Japanese adults. The authors postulate that bilateral occurrence of Carabelli tubercles was originally an inherited character in the molar region, but that the character was inhibited during the process of evolution of the masticatory system and regression of the molar dentition.

Background: The aim of this study was to retrospectively assess the usefulness of the preoperative oral cholecystogram (OCG) as an index to the feasibility of laparoscopic cholecystectomy (LC) and the operative pathologic findings. Laparoscopic cholecystectomy has become the standard treatment for symptomatic gallbladder (GB) disease. However, no definite diagnostic modality that can predict the feasibility of LC and severity of pathologic anatomy has been proposed. Methods: Retrospective data were collected on 240 consecutive patients undergoing LC at St. Vincent Hospital, Catholic University Medical College, from October 1991 until December 1993. Radiologic interpretations of OCG were standardized according to the method of Koehler and Kyaw—from grade 0 to 4. And the operative findings—pericholecystic adhesion, color of GB, and thickness of the GB wall—were evaluated simultaneously. Results: The analysis showed that preoperative OCG can predict intraoperative GB perforation (p = 0.022), intraoperative controllable bleeding (p = 0.034), and operating time (p = 0.0001) according to the grade of visualization of GB. Grade 2- or -better visualized groups had more patients who had blue-colored GB (p = 0.000) and who had thin GB wall (p =0.000). Conclusions: Preoperative oral cholecystogram may be an accurate index of the feasibility of laparoscopic cholecystectomy—represented by operating time and important intraoperative minor complications related to the operative pathologic findings.

Helicobacter pylori infection and nonsteroidal anti-inflammatory drug use are both common causes of peptic ulcer. It remains unclear whether H. pylori/NSAID interactions occur, and if they do, with what result(s).We prospectively evaluated development of gastric or duodenal ulcers in 181 arthritics followed for up to 3 months while receiving an NSAID chronically and with no active anti-ulcer medications. H. pylori status was determined with a sensitive, specific ELISA for anti-H. pylori IgG.H. pylori infection was present in 51%; peptic ulcers developed in 24. H. pylori infection was present in only 36% of those who developed a duodenal ulcer. Stepwise logistic regression analysis indicated none of the variable factors of age, gender, alcohol consumption, type of arthritis, or H. pylori status were significantly associated with development of peptic ulceration.These data suggest that H. pylori does not confer increased risk of ulceration in arthritics receiving NSAIDs chronically.

A novel member of the zinc finger superfamily was cloned by virtue of its binding to cis-regulatory elements of a glia-specific gene, the myelin proteolipid protein (PLP) gene. Named MyTI (myelin transcription factor I), this gene is most highly transcribed in the developing nervous system, where expression precedes induction of its presumptive target, PLP. Low levels of MyTI transcripts can be detected in nonneural tissues only by polymerase chain reaction analysis. Zinc is a necessary cofactor for DNA binding of MyTI, as the zinc-chelating agent 1,10-orthophenanthroline eliminates binding activity. Zinc may stabilize the DNA-binding domain of MyTI by coordinating three cysteine and one histidine residue in a Cys-X5-Cys-X12-His-X4-Cys (C2-HC) arrangement. The MyTI protein has six fingers of the C2-HC class arranged in two widely separated clusters. These two domains of DNA binding can function independently and recognize the same DNA sequence, suggesting that MyTI may contribute to the higher-order structure of a target promoter by simultaneously binding both proximal and distal sites. The six fingers are highly conserved, suggesting that they arose from successive duplication events, while the linker regions diverge in size and sequence. Both amino acid sequence comparisons and secondary-structure predictions indicate that the C2-HC fingers of MyTI do not resemble the zinc-mediated loops of C2-H2 fingers, C2-C2 fingers, or Cx clusters. MyTI may therefore be the prototype of a new structural family of zinc-stabilized DNA binding proteins.

Regulatory elements of the proteolipid protein (PLP) gene were identified physically by footprinting and gel mobility shift assays and functionally by transfecting glial cell lines with PLP-chloramphenicol acetyltransferase chimeric genes. In both human and rat glial cells, only several hundred base pairs of upstream sequence were sufficient for high level activity of the human PLP promoter. This region contains five sites that contact nuclear proteins in vitro. More distal recognition sites may exist, as regions upstream of -524 displayed silencing activity indicative of a negative regulatory element. A series of site directed mutations revealed one essential positive element (ATGGA at -118) which is found in other genes encoding myelin proteins. Our combined biochemical and functional analyses indicate that the key cis sites for maximal tissue-specific expression of PLP in cultured glial cells are clustered near the promoter. Within this cluster are several conserved motifs that may coordinate the regulation of myelin-specific genes.

A case of rudimentary polydactyly on the radial aspect of the thumb of a 4-year-old male was examined. Histologic examination revealed hyperkeratosis and acanthosis in the epidermis and large numbers of nerve bundles in the dermis. With immunoperoxidase staining for S-100 protein, the nerve corpuscles were positively stained. We think that rudimentary polydactyly is a kind of congenital traumatic neuroma and that the possible cause may be intrauterine amputation.

It has been shown that a TAA termed rat CEA had the tissue distribution and physico-chemical properties similar to those of human CEA. In addition, it has been demonstrated that these two antigens shared antigenic determinants. These findings supported our contention that rat CEA and human CEA are analogous moieties. The production of CEA-specific autoantibodies and the induction of resistance to CEA-positive rat tumors after immunization of rats with extracts containing rat CEA raises the possibility that human CEA may be immunogenic in man. Treatment with heat, proteolytic enzymes and periodate oxidation revealed that rat CEA, similar to human CEA contained both carbohydrate and protein epitopes. The epitopes shared by rat and human CEA that were detectable by the monkey anti-human CEA serum appeared to be carbohydrate, whereas the epitopes on rat CEA with which the rat mAb combined appeared to be protein, and those detected by the rabbit anti-rat CEA serum appeared to be carbohydrate, as well as protein. These studies also indicated that, although the rat, rabbit and monkey produced antibodies specific for rat CEA, the epitopes detectable by antibodies from one species appeared to be distinct from those detectable by antibodies from the other two species. These observations have important implications in studies on human CEA. Its use as a reliable diagnostic marker for malignancy hinges on the detection of tumor-specific epitopes on the molecule. Such epitopes have not yet been clearly identified by antibodies produced in foreign species. Indeed, our finding that the rat mAb to rat CEA bound only to tumor extracts and not to extracts of normal tissues, including intestinal tissues, suggests that human beings would be the most likely source of a tumor-specific antibody to human CEA. In future studies, the role antibodies play in immunity against CEA-positive tumors will be explored and attempts will be made to determine whether all of the serologically detectable epitopes on rat CEA can induce tumor resistance, or whether this activity is limited to epitopes detectable only by rat antibodies. This information could have important implications in the use of human CEA in the immunotherapy of malignancies.

Four patients developed severe burning feet after ingestion of the rodenticide RH-787 (Vaccor-B) attempting suicide. Parenteral administration of vitamin-B-complex relieved the symptom in all patients. Based on the results of these four patients and other data in the literature, vitamin-B-deficiency is discussed as a possible cause of burning feet.