[Night visual function of glaucoma patients with good photopic vision].

PURPOSE: To measure night visual function of glaucoma patients with good photopic vision. SUBJECTS AND METHODS: Patients aged 30-59 years who were diagnosed with glaucoma in the outpatient clinic of Nara Medical University, and showed a corrected visual acuity of > or = 1.0 in both eyes. The patients were classified using static threshold perimetry with a Humphrey field analyzer into two groups, with a mean deviation of -6 dB or better (early-stage glaucoma group) or a mean deviation worse than -6dB (intermediate/late-stage glaucoma group), and night visual function was measured. In addition, the patients were compared with normal controls without eye disease other than refractive error. RESULTS: The early-stage glaucoma group included 26 patients, and the intermediate/late-stage glaucoma group included 22 patients. There were 23 controls. Night visual function differed among the 3 groups. With the progression of visual field defects, the night visual function decreased. CONCLUSION: These results suggest that night visual function can be used as a new parameter for the evaluation of visual function in glaucoma patients.

A model teaching session for the hypothesis-driven physical examination.

INTRODUCTION: The physical examination is an essential clinical competence for all physicians. Most medical schools have students who learn the physical examination maneuvers using a head-to-toe approach. However, this promotes a rote approach to the physical exam, and it is not uncommon for students later on to fail to appreciate the meaning of abnormal findings and their contribution to the diagnostic reasoning process. The purpose of the project was to develop a model teaching session for the hypothesis-driven physical examination (HDPE) approach in which students could practice the physical examination in the context of diagnostic reasoning. METHODS: We used an action research methodology to create this HDPE model by developing a teaching session, implementing it over 100 times with approximately 700 students, conducting internal reflection and external evaluations, and making adjustments as needed. RESULTS: A model nine-step HDPE teaching session was developed, including: (1) orientation, (2) anticipation, (3) preparation, (4) role play, (5) discussion-1, (6) answers, (7) discussion-2, (8) demonstration and (9) reflection. DISCUSSIONS AND CONCLUSIONS: A structured model HDPE teaching session and tutor guide were developed into a workable instructional intervention. Faculty members are invited to teach the physical examination using this model.

Loss or down-regulation of HLA class I expression at the allelic level in freshly isolated leukemic blasts.

Loss or down-regulation of human leukocyte antigen (HLA) class I expression has been demonstrated in a variety of solid tumors. To date, such altered HLA expression has not been studied extensively in freshly isolated leukemic blasts. If it occurs, leukemic cells could escape T-cell surveillance as a consequence. Genotypes of nine leukemic cell lines were determined using a polymerase chain reaction for HLA classes I and II. Cells were also examined for HLA beta2-microglobulin, and allele-specific HLA protein expression using flow cytometry. Next, 44 samples of freshly isolated leukemic blasts from 43 patients with malignant hematological diseases were examined for allele-specific HLA expression using flow cytometry. Microsatellite analysis was performed to determine heterozygosity in the HLA region on chromosome 6. Genotype analysis for HLA class I together with microsatellite analysis demonstrated loss of HLA haplotype in HL-60 cells. No loss of HLA haplotype was observed in 44 samples of freshly isolated leukemic blasts. As reported previously, flow cytometric analysis rarely demonstrated loss or down-regulation of HLA expression at initial diagnosis (3/39; 7.7%); however, this was evident in two of five cases in relapse (40.0%), which contrasts with previous reports. In one patient with acute leukemia, HLA-A2 cell surface expression was present at initial diagnosis, lost at relapse, and completely restored after 48 h of culture in the presence of interferon-gamma. These results suggest loss of allele-specific HLA expression may be involved in the pathogenesis of relapse in patients with leukemia. The findings should be valuable in designing new strategies for clinical immunotherapy.

Relationship between corneal aberrations and contrast sensitivity after hyperopic laser in situ keratomileusis.

PURPOSE: To evaluate the relationship between corneal aberrations and contrast sensitivity (CS) after hyperopic laser in situ keratomileusis (H-LASIK). METHODS: In 13 patients (13 eyes) who underwent H-LASIK, we measured CS and corneal topography preoperatively and at 1 year postoperatively. Photopic and scotopic CS values were measured at 3, 6, and 12 cycles/degree (cpd) using an MCT-8000 contrast tester. Corneal aberrations were determined from the data on corneal topography using CTView. The corneal high-order aberrations were defined as the sum of the third- and fourth-order aberrations in the 4-mm zone and the sum of the third- to sixth-order aberrations in the 6-mm-zone. RESULTS: Under scotopic conditions at 12 cpd, the changes in CS significantly correlated with changes in the corneal aberrations. Scotopic CS was significantly deteriorated by glare, but photopic CS was not significantly changed. H-LASIK induced a significant increase in corneal aberrations that positively correlated with the amount of correction, regardless of the improvement in logMAR corrected visual acuity. LogMAR corrected visual acuity did not significantly correlate with corneal aberrations. Furthermore, decentration significantly correlated with the changes in the 6-mm zone corneal aberrations. CONCLUSIONS: In eyes after H-LASIK, the changes in scotopic CS significantly correlated with those in the corneal aberrations, which might have resulted from decentration or ablation profiles in H-LASIK and a relatively small optical zone. Further studies will be needed to validate this relationship.

Serum cytokine concentrations and acute graft-versus-host disease after allogeneic peripheral blood stem cell transplantation: concurrent measurement of ten cytokines and their respective ratios using cytometric bead array.

Both inflammatory and anti-inflammatory cytokines have been reported to be associated with acute graft-versus-host disease (aGVHD). However, their role and possible mutual interactions during aGVHD are not well understood. Eight patients with aGVHD and eight without who had undergone allogeneic HLA-identical peripheral blood stem cell transplantation were studied. The patients had no other complications known to affect serum concentration of cytokines, including infection. Serum concentrations of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-alpha and IFN-gamma were concurrently measured by a new technique, the cytometric bead array (CBA). We found that serum concentrations of IL-5, IL-6 and IL-10 were significantly higher in patients with aGVHD than in patients without it. By ratiometric analysis, the ratios of IL-5/IL-2, IL-5/IL-4, IL-6/IL-4 in patients with aGVHD were increased compared to the patients with no evidence of aGVHD. ROC analysis demonstrated that the ratio of IL-5/IL-4 was the most sensitive parameter associated with aGVHD. The second best marker of aGVHD was increased IL-5 concentration. Thus, our results indicate that the ratio of a particular cytokine/cytokine could be a potential diagnostic marker for aGVHD, more sensitive that the serum level of a given cytokine. This observation is consistent with a cross-talk among some cytokines and their possible interactions via respective receptors on cytokine-producing cells; these interactions may play an important role in pathogenesis of aGVHD. Further studies including a large number of patients and concurrent measurement of a variety of cytokines are needed to fully assess the diagnostic value of the cytokine ratiometric analysis. The CBA methodology provides a convenient and useful tool in such studies.

Evaluation of apparent ectasia of the posterior surface of the cornea after keratorefractive surgery.

PURPOSE: To calculate the apparent posterior corneal changes after keratorefractive surgery and reevaluate corneal ectasia displayed by Orbscan (Orbtek). SETTING: Department of Ophthalmology, Nara Medical University, Nara, Japan. METHODS: Postoperative:preoperative magnification ratio of the posterior surface of the cornea was calculated in a theoretical eye model. RESULTS: Assuming the preoperative corneal thickness is 600.00 microm, the preoperative refractive power of the anterior corneal surface is 48.0 diopters (D), the refractive power of the cornea is 1.376, the ablation diameter is 6.0 mm, the postoperative corneal thickness is 480.00 microm, the postoperative refractive power of the anterior corneal surface is 38.0 D, and the posterior surface of the cornea does not change postoperatively, the apparent image of the posterior surface of the cornea becomes 0.778% smaller postoperatively. If the posterior radius of curvature of the cornea is 6.2 mm, it becomes smaller by 48.24 microm. If this change directly affects the difference map, the posterior surface of the cornea moves forward by 48.24 microm. CONCLUSION: The results correspond to the amount of ectasia in previous reports. This artifact may explain the apparent ectasia detected by Orbscan.

Expression of SOCS3 mRNA in bone marrow cells from CML patients associated with cytogenetic response to IFN-alpha.

Previously, we have demonstrated that constitutive expression of suppressor of cytokine signaling-3 (SOCS3) affects the sensitivity of chronic myelogenous leukemia (CML) cell lines to interferon-alpha (IFN-alpha). In the present study, we analyzed the expression of SOCS3 mRNA in bone marrow cells from patients with CML at diagnosis, with the aid of real-time polymerase chain reaction. SOCS3 mRNA expression in bone marrow cells from CML patients who responded well to IFN-alpha therapy was significantly lower than that in cells from healthy volunteers and patients who were resistant to IFN-alpha therapy. Methylation of SOCS3 promoter was absent in bone marrow cells from all CML patients examined. These results indicate that the expression of SOCS3 mRNA is inversely associated with the sensitivity to IFN-alpha both in vitro and in vivo and that differences in SOCS3 mRNA expression are not due to the methylation status of SOCS3 promoters.

Posterior corneal surface changes after hyperopic laser in situ keratomileusis.

PURPOSE: To evaluate posterior corneal surface topographic changes after hyperopic laser in situ keratomileusis (H-LASIK) using Orbscan I (Orbtek, Inc.). SETTING: Department of Ophthalmology, Nara Medical University, Nara, Japan. METHODS: In 25 eyes of 15 patients who had H-LASIK, the posterior corneal surface was measured with slit-scanning corneal topography (Orbscan I) preoperatively and 1 year postoperatively. The center as a fit zone and calculated posterior corneal surface changes were taken at 4 points: nasal, temporal, superior, and inferior sides in the 5.0 mm diameter. The posterior corneal topographic changes were analyzed using an analysis of variance. The postoperative:preoperative magnification ratio of the posterior corneal surface was calculated in a theoretical eye model. RESULTS: When a "+" reading was defined as the forward displacement and "-" was defined as the backward displacement, the mean posterior corneal topographic changes were -2.8 microm +/- 27.9 (SD) at the nasal side, -4.5 +/- 27.8 microm at the temporal side, -3.9 +/- 20.1 microm at the superior side, and -2.3 +/- 20.1 microm at the inferior side. The posterior corneal surface between any 2 examined points showed no significant difference after H-LASIK. In addition, the hypothetical change in the posterior cornea was -8.3 microm after +3.0 diopter H-LASIK, which was approximately closer to the study results. In each side, the amount of the attempted correction was significantly correlated with the posterior corneal topographic change. CONCLUSIONS: Clinical measurement of the posterior corneal displacement after H-LASIK with Orbscan revealed a backward shift. This change corresponded to the hypothetical artifactual changes with Orbscan; that is, changes in the magnification ratio.

High frequency of allele-specific down-regulation of HLA class I expression in lung cancer cell lines.

Loss or down-regulation of HLA expression has been demonstrated in various types of solid tumors and is considered to be one of the mechanisms of tumor immunoescape. The effectiveness of immunotherapy using tumor-specific antigens (TSA) largely depends on the expression of the appropriate HLA class I alleles on the tumor cells. We analyzed the allele-specific HLA class I surface expression of six lung cancer cell lines using a broad panel of allele-specific monoclonal antibodies, as well as the effect of IFN-gamma on HLA expression. Flow cytometric analysis displayed a wide range, from minimal to a high degree of expression of monomorphic HLA class I among the studied cell lines. Allele-specific loss or down-regulation of HLA also was observed in 5 out of 6 cell lines. Our results suggest that lung cancer patients considered for specific immunotherapy should be examined with respect to the expression of specific HLA class I allele binding the TSA.

Peripheral blood circulating immature cell counts predict CD34+ cell yields in G-CSF-induced PBPC mobilization in healthy donors.

BACKGROUND: It has been previously reported that the number of circulating immature cells (CIC) in peripheral blood (PB) estimates the number of CD34+ cells collected in G-CSF plus chemotherapy-induced PBPC mobilization. The correlation of CIC counts in PB with CD34+ cell yield and its usefulness was evaluated in G-CSF-induced PBPC mobilization for healthy donors. STUDY DESIGN AND METHODS: CIC counts in PB and CD34+ cell counts in the apheresis product from 122 collections were assessed, and the relationship between these two variables was evaluated with the Pearson rank correlation analysis, the chi-squared test, and the U-test. RESULTS: CIC counts were correlated weakly with the number of CD34+ cells per L of blood processed in the apheresis product (Pearson rank correlation analysis; r=0.357, p<0.0001). When a level of 1.7 x 10(9) CICs per L was selected as a cutoff value, the sensitivity and specificity for collecting more than 20 x 10(6) CD34+ cells per L of blood processed were 63.6 and 77.5 percent, respectively. CONCLUSION: The present study suggests that the number of CICs in PB may estimate the number of CD34+ cells collected. The data indicate that CIC counts above 1.7 x 10(9) per L can be used as a good predictor for PBPC collections containing more than 20 x 10(6) CD34+ cells per L of blood processed in a single apheresis procedure.

Factors affecting successful palliative surgery for malignant bowel obstruction due to peritoneal dissemination from colorectal cancer.

BACKGROUND: Nonresectable colorectal cancer often causes malignant intestinal obstruction due to peritoneal dissemination. However, no previous report has specifically investigated which patients, with peritoneal dissemination from colorectal cancer, would actually benefit from palliative surgery. This study defines the selection criteria for patients who are likely to benefit from palliative surgery. METHODS: Twenty-one patients underwent palliative surgery for malignant bowel obstruction due to peritoneal dissemination from colorectal cancer. In all cases, the advanced and nonresectable nature of the tumor was confirmed at laparotomy. Clinical factors such as age, gender, serum level of carcinoembryonic antigen, amount of ascites, location of the primary cancer, surgical procedure, and postoperative chemotherapy were analyzed for prognostic significance in symptom-free and overall survival using the Kaplan-Meier product limit method and the log-rank test. RESULTS: All the postoperative courses were uneventful. Obstruction recurred after a median symptom-free interval of 61 days in the group with less than 100 ml of ascites, whereas it recurred after 9 days in the group with more than 100 ml of ascites. Symptom-free survival rates in patients who manifested ascites were significantly lower than in those without ascites (P = 0.0321, log-rank method). The symptom-free and overall survival rates in patients who underwent postoperative chemotherapy were significantly higher (P = 0.0225 and 0.0003). CONCLUSIONS: Palliative surgery can be performed effectively for patients without ascites. For patients who do not meet this criterion, a non-surgical procedure may be preferable.

Evaluation of the corneal endothelium after hyperopic laser in situ keratomileusis.

PURPOSE: To evaluate corneal endothelial changes after hyperopic laser in situ keratomileusis (LASIK) considering overestimation and underestimation of the cell count measurement. SETTING: Department of Ophthalmology, Nara Medical University, Nara, Japan. METHODS: The data were from the clinical trial of the Nidek EC-5000 excimer laser for hyperopic LASIK. The mean correction was 3.59 diopters (D) +/- 1.54 (SD) (range 2.0 to 6.0 D). Using noncontact specular microscopy, the corneal endothelial changes in 25 eyes of 15 patients who had hyperopic LASIK were measured. Follow-up ranged from 6 months (n = 25) to 1 year (n = 21). The overestimation and underestimation of the corneal endothelial cell count that would occur after +5.0 D hyperopic LASIK was hypothetically calculated. RESULTS: The measured endothelial cell count per 1.0 mm(2) did not significantly decrease up to 1 year after hyperopic LASIK (preoperatively, 2508 +/- 395; at 1 year, 2814 +/- 349). The hypothetical calculation revealed that a +5.0 D hyperopic correction corresponded to a 0.1% underestimation of the corneal endothelial cell count. CONCLUSIONS: Underestimation of the corneal endothelial cell count after hyperopic LASIK was negligible. Hyperopic LASIK with the Nidek EC-5000 excimer laser did not significantly decrease corneal endothelial cells up to 1 year after surgery.

[A study on cases of good apparent accommodation using an all-distance visual acuity chart and corneal shape analysis].

PURPOSE: As a part of an attempt to elucidate the mechanism of apparent accommodation, an evaluation was made of patients with good apparent accommodation using an all-distance visual acuity chart and corneal shape analysis. MATERIALS AND METHODS: The study was performed on 6 patients (7 eyes) in a good apparent accommodation group and 13 patients (15 eyes) in a poor apparent accommodation group. These were selected from patients who had undergone normal small-incision ultrasonic phacoemulsification and posterior chamber type single focus intraocular lens implantation. In these patients, all-distance visual acuity was measured using an AS-15(Kowa Co., Ltd.), and corneal shape analysis was performed using Orbscan (Orbtek Inc.). RESULTS: In all-distance visual acuity, gentle decline from far to near was noted in the poor apparent accommodation group, and the degree of decline was lower in the good apparent accommodation group. Also, a two-peak pattern, showing decline at first and then an increase, was observed in some of the cases. In corneal shape analysis, there was no specific pattern in the good apparent accommodation group. However, the difference between maximum refractive power and minimum refractive power of cornea in the ranges of 3, 5, and 7 mm in total optical power (TOP) was significantly higher in the good apparent accommodation group compared with the poor apparent accommodation group (TOP 3 mm: p = 0.0233, TOP 5 mm: p = 0.0306, TOP 7 mm: p = 0.0035). CONCLUSION: In the present study, there were three patterns in all-distance visual acuity in the good apparent accommodation group, showing a two-peak pattern, a flat pattern, and a gentle decline, and the pattern of gentle decline was observed more often than the other patterns. The results of the study also suggest that the gradient of corneal refractive power may be related to apparent accommodation.

Differentiation of monoblastic cell line UG3 into leukemic dendritic cells.

Dendritic cells (DCs) are known to be generated from leukemic clone from patients with acute and chronic leukemia when cultured in the presence of combination of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha) and interleukin-4. However, there have been few reports that showed DCs could be effectively differentiated from human leukemia cell lines. In this study, we have shown that a human monoblastic cell line, UG3, was inducible to differentiate into DCs in the presence of GM-CSF and TNF-alpha along monocyte-macrophage lineage. These DCs, consistently displayed dendritic morphology, phenotypes and allogeneic T-cell stimulating capacity. UG3 cells thus may represent a suitable model to further elucidate characteristics of DC differentiation.