The previously reported repositioning methods have been known to be very difficult to be performed. A new external knotting technique was performed to reposition the dislocated intraocular lenses (IOLs). After 3-port vitrectomy, a 30 gauge injecting needle tip into which the thread end of a 10-0 polypropylene was put, was introduced into the vitreous cavity through the ciliary sulcus to make a loop having an external knot. After one haptic of the IOL was engaged into the loop, the thread was pulled back and tied to make a knot. After holding and pulling the haptic of the IOL with the intraocular forceps for proper position of the knot. Then it was sutured and fixed in sclera. The IOLs were kept in central position without complications. The final visual outcome was 0.8 and 0.3 respectively. This method might be safe and easy to correct the dislocated IOL.
Lenses, Intraocular* ; Needles ; Polypropylenes ; Sclera ; Surgical Instruments ; Vitrectomy

PURPOSE: Uptakes of Tc-99m MIBI (MIBI) and Tc-99m tetrofosmin (tetrofosmin) in human non-small cell lung cancer A549, multidrug-resistance associated protein (MRP) expressing cell, were investigated in vitro and in vivo. MATERIALS AND METHODS: Western blot analysis and immunohistochemistry were used for detection of MRP in A549 cells with anti-MRPr1 antibody. Cellular uptakes of two tracers were evaluated at 100 umM of verapamil (Vrp), 50 umM of cyclosporin A (CsA) and 25 umM of butoxysulfoximide (BSO) after incubation with MIBI and tetrofosmin for 30 and 60 min at 37degrees C, using single cell suspensions at 1x10 (6) cells/ml. Radioactivities in supernatants and pellets were measured with gamma well counter. A549 cells were inoculated in each flanks of 24 nude mice. Group 1 (Gr1) and Gr3 mice were treated with only MIBI or tetrofosmin, and Gr2 and Gr4 mice were treated with 70mg/kg of CsA i.p. for 1 hour before injection of 370KBq of MIBI or tetrofosmin. Mice were sacrificed at 10, 60 and 240 min. Radioactivities of organs and tumors were expressed as percentage injected dose per gram of tissue (%ID/gm). RESULTS: Western blot analysis of the A549 cells detected expression of MRPr1 (190 kDa) and immunohistochemical staining of tumor tissue for MRPr1 revealed brownish staining in cell membrane but not P-gp. Upon incubating A549 cells for 60 min with MIBI and tetrofosmin, cellular uptake of MIBI was higher than that of tetrofosmin. Coincubation with modulators resulted in an increase in cellular uptakes of MIBI and tetrofosmin. Percentage increase of MIBI was higher than that of tetrofosmin with Vrp by 623% and 427%, CsA by 753% and 629% and BSO by 219% and 140%, respectively. There was no significant difference in tumoral uptakes of MIBI and tetrofosmin between Gr1 and Gr3. Percentage increases in MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively higher by the time up to 240 min with CsA. CONCLUSION: These results indicate that MIBI and tetrofosmin are suitable tracers for imaging MRP-mediated drug resistance in A549 tumors. MIBI may be a better tracer than tetrofosmin for evaluating MRP reversal effect of modulators.
Animals ; Blotting, Western ; Carcinoma, Non-Small-Cell Lung ; Cell Membrane ; Cyclosporine ; Drug Resistance ; Humans ; Immunohistochemistry ; Mice ; Mice, Nude ; Multidrug Resistance-Associated Proteins ; P-Glycoprotein ; Radioactivity ; Suspensions ; Verapamil

PURPOSE: Cellular uptakes of 99mTc-sestamibi (MIBI) and 99mTc-tetrofosmin into cancer cell lines expressing multidrug resistance (MDR) were investigated and compared. The effects of verapamil and cyclosporin A, well-known multidrug resistant reversing agents, on cellular uptakes of both tracers were also compared. MATERIALS AND METHODS: Doxorubicin-resistant HCT15/CL02 human colorectal cell and doxorubicin-resistant K562 (Adr) and vincristine-resistant K562 (Vcr) human leukemic cells were studied. RT-PCR analysis was used for the detection of mdr1 mRNA expression. MDR-reversal effects with verapamil and cyclosporine A were evaluated at different drug concentrations after incubation with MIBI and tetrofosmin for 1, 15, 30, 45 and 60 min, using single-cell suspensions at 1x10 (6) cells/ml incubated at 37 degrees C. Radioactivity in supernatants and pellets were measured with gamma well counter. RESULTS: The cellular uptakes of MIBI and tetrofosmin in K562 (Adr) and K562 (Vcr) were lower than those of parental K562 cell. In HCT15/CL02 cells and K562 (Adr) cells, there were no significant difference in cellular uptakes of both tracers, but cellular uptake of MIBI was higher than that of tetrofosmin in K562 (Vcr) cells. Coincubation with verapamil resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Verapamil increased cellular uptakes of MIBI and tetrofosmin by HCT15/CL02 cell by 11.9- and 6.8-fold, by K562 (Adr) cell by 14.3- and 8-fold and by K562 (Vcr) cell by 7- and 5.7-fold in maximum, respectively. Cyclosporin A increased cellular uptakes of MIBI and tetrofosmin by HCT15/CL02 cell by 10- and 2.4-fold, by K562 (Adr) cell by 44- and 13-fold and by K562 (Vcr) cell by 18.8- and 11.8-fold in maximum, respectively. CONCLUSION: Taking together, MIBI and tetrofosmin are considered as suitable radiopharmaceuticals for detecting multidrug resistance. However, MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators. Since cellular uptakes of both tracers might differ in different cell types, further experiments regarding differences in cellular uptakes between cell types should be explored.
Cell Line* ; Cyclosporine ; Drug Resistance, Multiple* ; Humans ; Parents ; Radioactivity ; Radiopharmaceuticals ; RNA, Messenger ; Suspensions ; Technetium Tc 99m Sestamibi* ; Verapamil

PURPOSE: Cellular uptake of 99mTc-sestamibi (MIBI) and 99mTc-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance (MDR) by p-glycoprotein (Pgp) or multidrug related protein (MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. MATERIALS AND METHODS: Cellular uptakes of Tc-99m MIBI and TF were measured in erythroleukemia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562 (Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto 200 micro M at 1x10 (6) cells/ml at 37degrees C. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. RESULTS: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562 (Adr) cell at a concentration of 100 micro M and the maximal increase at 50 micro M was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over 1 micro M. With a concentration of 200 micro M verapamil, MIBI and TF uptakes in K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with 10 micro M, but were also decreased with verapamil higher than 10 micro M, resulting 40% and 5% of baseline at 50 micro M. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at 200 micro M. CONCLUSION: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.
Blotting, Western ; Breast Neoplasms ; Cell Line ; Drug Resistance, Multiple ; Humans ; K562 Cells ; Leukemia, Erythroblastic, Acute ; MCF-7 Cells ; Ovarian Neoplasms ; P-Glycoprotein ; Radioactivity ; RNA, Messenger ; Technetium Tc 99m Sestamibi ; Verapamil*

OBJECTIVE: The purpose of this study is to evaluate the clinical and hematological effects of tocilizumab in active rheumatoid arthritis (RA) patients. METHODS: Fourteen patients with active RA were enrolled in this study. The patients received tocilizumab 8 mg/kg intravenously every four weeks for 6 months. Disease activity, anemia-related factors including serum hepcidin-25, and hematological parameters were monitored at baseline and at 1, 3, and 6 months after the initiation of treatment. RESULTS: Significant reductions in tender joint count, swollen joint count, visual analogue scale, erythrocyte sedimentation rate (ESR), and C-reactive (CRP) protein plus reductions in a 28-joint disease activity score were observed within one month after the first tocilizumab treatment. These effects lasted throughout the six-month study period. In addition, significant improvements in anemia-related factors such as hepcidin-25, ferritin, iron, hemoglobin, red blood cell counts and mean corpuscular volume were observed during the treatment period. Hematological parameters were improved with reductions in counts for leukocytes, monocytes, neutrophils, and platelets. The lymphocyte counts and their subset numbers were unchanged. Changes in hepcidin levels showed significant correlation with changes in CRP, ESR, ferritin, hemoglobin and counts for red blood cells, leukocytes, and neutrophils during the treatment period. CONCLUSION: This study demonstrates that tocilizumab significantly and meaningfully reduces disease burden in patients with active RA. In addition, tocilizumab diminishes the levels of inflammatory anemia by inhibiting hepcidin production. These clinical data provide evidence of a favorable outcome from tocilizumab in RA.
Anemia* ; Arthritis, Rheumatoid* ; Blood Sedimentation ; Erythrocyte Count ; Erythrocyte Indices ; Erythrocytes ; Ferritins ; Hepcidins* ; Humans ; Iron ; Joints ; Leukocytes ; Lymphocyte Count ; Monocytes ; Neutrophils

OBJECTIVE: To evaluate the laboratory and clinical manifestations of Sjögren's syndrome (SS) association with chemokine (C-X-C motif) ligand 1 (CXCL1) expression in the ductal and acinar salivary gland epithelial cells (SGEC) of the minor salivary glands. METHODS: The sociodemographic data of 106 SS patients was obtained, and the glandular and extraglandular manifestations of the disease documented. The minor salivary glands were biopsied and the laboratory findings analyzed. European League Against Rheumatism SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) scores were obtained during biopsy. An immunohistochemical approach was used to define the expression of CXCL1 in the salivary glands. RESULTS: Of 106 patients, the minor salivary glands of 22 patients (20.7%) stained positively for CXCL1. Such CXCL1-positive patients exhibited higher ESSDAI scores at the time of biopsy than the CXCL1-negative patients (3.86±2.27 vs. 2.64±1.62, p=0.015). Lymphadenopathy was more frequently observed in CXCL1-positive patients, compared with CXCL1-negative patients (31.8% vs. 9.5%, p=0.014). No differences between groups were identified in terms of sociodemographic characteristics, laboratory data, or the extent of the glandular manifestation of SS. CONCLUSION: The expression of CXCL1 within the ductal and acinar SGEC of SS patients is associated with lymphadenopathy and elevated clinical disease activity. CXCL1 may play an important role in the disease activity and prognosis of SS.
Biopsy ; Chemokine CXCL1* ; Chemokines ; Epithelial Cells ; Humans ; Lymphatic Diseases ; Prognosis ; Rheumatic Diseases ; Salivary Glands ; Salivary Glands, Minor*

We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjogren's syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.
Adult ; Autoantibodies/blood ; C-Reactive Protein/analysis ; Demography ; Female ; Germinal Center/*pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Receptors, Complement 3d/metabolism ; Retrospective Studies ; Salivary Glands, Minor/*pathology ; Sjogren's Syndrome/immunology/metabolism/*pathology

We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjogren's syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.
Adult ; Autoantibodies/blood ; C-Reactive Protein/analysis ; Demography ; Female ; Germinal Center/*pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Receptors, Complement 3d/metabolism ; Retrospective Studies ; Salivary Glands, Minor/*pathology ; Sjogren's Syndrome/immunology/metabolism/*pathology

BACKGROUND: The combination chemotherapy of gemcitabine and cisplatin has been proven effective in the treatment of advanced non-small cell lung cancer (NSCLC). However, the optimal schedule for administration of the two drugs has not yet been determined. We therefore started a phase II trial to evaluate efficacy, toxicity and dose intensity (DI) as three-week scheduled chemotherapy of gemcitabine and cisplatin. METHODS: Between October 2000 and March 2003, a total of 56 patients with stage IIIB and IV NSCLC were enrolled in this study. Treatment schedule consisted of gemcitabine 1200 mg/m2 i.v. on days 1 and 8, and cisplatin 80 mg/m2 i.v. on day 1 of each chemotherapy cycle followed by two weeks of rest. RESULTS: Forty-eight patients were evaluable in response and adverse effects in this study. The median DI was 529 mg/m2/week for gemcitabine (66%) and 22 mg/m2/week for cisplatin (83%). Partial response was observed in 23 patients. The overall response rate was 47.8% (95% confidence interval [CI], range from 33.6% to 61.9%). Anemia and thrombocytopenia were the main hematologic adverse effects, with 8.3% and 8.3% of patients experiencing grade III to IV toxicity, respectively. The median survival time was 11.78 months (95% CI, range from 8.59 to 14.97months). No significant differences in response rate were observed according to sex, age, histology and DI of gemcitabine and cisplatin. CONCLUSION: The 3-week-scheduled combination chemotherapy of gemcitabine and cisplatin has feasibility to treat advanced stage IIIB and IV NSCLC with modest adverse effects. The regimen deserves further evaluaton in a phase III prospective randomized trial.
Anemia ; Appointments and Schedules ; Carcinoma, Non-Small-Cell Lung ; Cisplatin* ; Drug Therapy ; Drug Therapy, Combination* ; Humans ; Thrombocytopenia

OBJECTIVES: The aim of this study was to investigate brain activation during a Korean language-based 'theory of mind (TOM)' task and fMRI in Korean schizophrenic patients. METHODS: Fourteen Korean schizophrenic patients and 15 normal controls participated in this study. For all participants, several clinical states and psychosocial functions were evaluated. The subjects were then scanned while performing Korean language-based fMRI tasks. The tasks were comprised of conditions-first order false belief (TOM task), physical causality, and unrelated situations. Imaging data were analyzed using SPM2 software (uncorrected p<0.005, extent threshold kappa=10). RESULTS: 1) Compared with the control group, the patient group showed significantly poorer performance on the TOM task, and no significant correlation between TOM and empathic abilitiesy. 2) In the patient group, there were no significantly activated brain regions associated with the TOM task as compared to the physical causality task. With respect to between-group differences, the patient group showed significantly less activation of the left medial frontal region (primarily BA 8) and signifcantly different activation of the left precuneus (BA 7) associated with the TOM task. CONCLUSION: These results suggest that Korean schizophreniac patients show different brain activity associated with TOM functions, especially with respect to the Korean language-based first order false belief tasks.
Brain ; Humans ; Magnetic Resonance Imaging ; Schizophrenia ; Theory of Mind