High Frequency of Hepatitis B Core and Surface Antibodies in Hepatitis C Virus-Infected Patients on the Screening Examination.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are important human pathogens that cause chronic liver disease and hepatocellular carcinoma. Co-infection of HBV and HCV is not uncommon, particularly in countries where these two viruses are endemic. Therefore, the characteristics of HBV co-infection in HCV antibody (HCVAb) -positive Japanese patients found on the screening examination were analyzed. PATIENTS AND METHODS: Between January and December 2011, HCVAb status was evaluated as the screening examination in 12,582 patients in Gunma University Hospital, and it was positive in 402 patients (3.2%). In 331 HCVAb-positive/HBs antigen (HBsAg) -negative patients with available residual serum, HBs antibody (HBsAb) and HBc antibody (HBcAb) were examined. In addition, HCV-RNA was examined in 291 patients with available residual serum. HBV-DNA and HBV core-related antigen (HBcrAg) were examined in 106 patients with available residual serum. RESULTS: The HCVAb titer was distributed between 1 and 18 sample/cutoff index (S/CO). 275 patients (83.1%) had a high HCVAb titer (S/CO ≥10). HCV-RNA was positive in 230 (79.0%) patients, and it was more frequently detected in HCVAb high-titer patients (88%) than in low-titer patients (32%; p < 0.0001); 61 (18.4%) and 101(30.5%) patients were positive for HBsAb and HBcAb, respectively. Of 230 HCV-RNA-positive patients, 38 (16.5%) and 59 (25.6%) were positive for HBsAb and HBcAb, respectively. Three (2.8%) and 2 (1.9%) of 106 patients had HBV-DNA and HBVCrAg. The ALT level was higher than 30 IU/L in 146/327 (44.6%) HCVAb-positive patients who had ALT levels measured. Abnormal ALT elevation was more frequent in HCVAb high-titer patients than in low-titer patients (48.3% vs. 26.8%; p = 0.0031), and in HCV-RNA-positive patients than in HCV-RNA-negative patients (54.2% vs. 13.3%; p < 0.001). CONCLUSION: HBV reactivation should be noted in these HCVAb-positive/HBsAg-negative patients on the screening examination if these patients must receive chemotherapy or immunosuppressive therapy. In addition, surveying of HBsAb in addition to HBcAb is also necessary.

High percentage of regulatory T cells before and after vitamin B12 treatment in patients with pernicious anemia.

INTRODUCTION: In some previous studies, vitamin B12 treatment showed immunomodulatory effects and restored the immunological abnormalities in patients with pernicious anemia (PA). In the present study, peripheral blood T cell subsets, including regulatory T cells (T(reg)s), were examined before and after vitamin B12 treatment in PA patients. PATIENTS AND METHODS: The percentages of CD4, CD8, Th1, Th2 and T(reg)s were examined in 23 PA patients before vitamin B12 treatment, in 23 other PA patients after vitamin B12 treatment and in 28 healthy controls. RESULTS: The mean percentage of CD8+ T cells was significantly higher in the control group (23.0%; 95% CI, 20.4-25.6%) than in the pre- (16.0%; 95% CI, 12.1-20.0%) and posttreatment groups (15.2%; 95% CI, 11.8-18.6%; p < 0.05). The CD4/CD8 ratio was significantly lower in the control group (2.01; 95% CI, 1.66-2.34) than in the pre- (3.45; 95% CI, 2.55-7.80) and posttreatment groups (2.97; 95% CI, 2.22-3.72; p < 0.05). There was no significant difference in the mean Th1/Th2 ratio among these groups. There were significant increases in the mean percentage of T(reg)s in the pre- (6.29%; 95% CI, 5.04-7.54%) and posttreatment groups (7.77%; 95% CI, 6.34-9.20%) compared with the control group (4.18%; 95% CI, 3.92-4.47%; p < 0.05). CONCLUSIONS: The percentage of T(reg)s was significantly higher in PA patients than in normal subjects, and this high T(reg) percentage was not different before and after vitamin B12 treatment. Other immunological alterations also did not recover after vitamin B12 treatment, so that these immunological changes appear to be the cause of PA and are not induced by vitamin B12 deficiency.

Attitudes toward interprofessional healthcare teams: a comparison between undergraduate students and alumni.

The goal of effective interprofessional education (IPE) is high-quality patient-care delivery and attaining a high level of patient satisfaction in clinical settings. We aimed to examine if alumni who have studied in an IPE program at a pre-licensure stage maintain a positive attitude toward collaborative practice (CP) in the postgraduate clinical experience. This paper presents a cross-sectional descriptive study which employed the modified attitudes toward health care teams scale (ATHCTS) to examine the relationship between exposure to clinical practice and the attitudes toward interprofessional healthcare teams. Results indicated that the overall mean score of alumni was significantly lower than that of undergraduate students on the modified ATHCTS. Only "team efficacy" had a significantly lower regression factor score in alumni than undergraduate students. Our findings suggest that changes in professional identity in a team may be due to contact with patients after graduation in the postgraduate clinical healthcare experience. The reduction of attitudes toward healthcare teams in the postgraduate clinical experience may be related to "team efficacy". We emphasize the need for in-service IPE for sustaining attitudes and providing a useful CP, which results in good clinical outcome.

[Improvement in peripheral blood T cell subset imbalance in a house with an elimination system for various allergens].

We analyzed the change of peripheral blood T cell subsets after moving into a house with a Healthy Air system (HAS) elimination system for various allergens, e.g. pollens, house dusts, etc. The 20 subjects were divided into an allergic group (13 subjects) and control group (7 subjects). We measured complete blood counts (CBC), white blood cell differentiation (DIFF), CD4/CD8 ratio, Th1/Th2 ratio, and percentage of CD4+CD25+T-cells and regulatory T-cells in peripheral blood, and these data were compared before and 3 and 6 months after moving into the HAS house. There was no significant difference in CBC, DIFF, CD4/CD8 ratio, and Th1/Th2 ratio before and after the move. The mean levels and 95% confidence interval of CD4+CD25+T-cells in the allergic group were as follows: before, 16.66% (12.99-20.34%); at 3 months, 13.86% (10.49-17.22%); and at 6 months, 12.66% (9.28-16.05%), respectively. Those in the control group were as follows: before, 13.60% (5.27-21.93%); at 3 months, 12.51%(5.41-19.61%); and at 6 months, 11.77% (3.93-19.61%), respectively. CD4+CD25+T-cells were significantly decreased at 6 months after the move compared to before the move in the allergic group (p < 0.01). However, there was no significant difference between before and after the move in the control group. The mean levels of regulatory T-cells were not different between before and after the move in both groups. The mean level of CD4+CD25+T-cells in subjects that had improved allergic condition was significantly decreased at 6 months after the move compared to before the move (p < 0.05). These results suggest that decreases in allergens in the home environment may affect lymphocyte subsets.

Clinical Significance of Peripheral Blood T Lymphocyte Subsets in Helicobacter pylori-Infected Patients.

Background. Helicobacter pylori chronically colonizes gastric/duodenal mucosa and induces gastroduodenal disease and vigorous humoral and cellular immune responses. Methods. In order to clarify the immunological changes induced by this infection, we determined the percentage and, as indicated, ratios of the following cells in peripheral blood of 45 H. pylori-infected patients and 21 control subjects: CD4(+) T cell, CD8(+) T cells, T helper 1 cells (Th1), T helper 2 cells (Th2), CD4(+)CD25(+) T cells, Foxp3(+) regulatory T cells (Tregs), CD4/CD8 ratio, and Th1/Th2 ratio. Results. The percentage of CD8(+) T cells was significantly lower in H. pylori-infected patients (mean ± SD; 18.0 ± 7.1%) compared to control subjects (mean ± SD; 23.2 ± 7.8%) (P < 0.05). The CD4/CD8 ratio was significantly higher in H. pylori-infected patients (mean ± SD; 3.1 ± 2.4) compared to control subjects (mean ± SD; 2.1 ± 1.0) (P < 0.05). The Th1/Th2 ratio was significantly lower in H. pylori-infected patients (mean ± SD; 10.0 ± 8.5) compared to control subjects (mean ± SD; 14.5 ± 9.0) (P < 0.05). The percentage of CD4(+)CD25(+) T cells in H. pylori-infected patients (mean ± SD; 13.2 ± 6.2%) was significantly higher than that in control subjects (mean ± SD; 9.8 ± 3.4%) (P < 0.05). However, there was no significant difference in Tregs. Conclusion. Tregs did not decrease, but the activation of humoral immunity and Th2 polarization were observed in the peripheral blood of H. pylori-infected patients. In some cases, these changes may induce systemic autoimmune diseases.

Changes in attitudes toward interprofessional health care teams and education in the first- and third-year undergraduate students.

The interprofessional education (IPE) program at Gunma University, Maebashi, Japan, implements a lecture style for the first-year students and a training style for the third-year students. Changes in the scores of modified Attitudes Toward Health Care Teams Scale (ATHCTS) and those of modified Readiness of health care students for Interprofessional Learning Scale (RIPLS) at the beginning and the end of the term were evaluated in the 2008 academic year. Two hundred and eighty-five respondents of a possible 364 completed the survey. In both the scales, the overall mean scores declined significantly after the lecture-style learning in the first-year students, while the scores improved significantly after the training-style learning in the third-year students. Exploratory factor analysis revealed that the modified ATHCTS was composed of three subscales, and the modified RIPLS two subscales. Analyses using regression factor scores revealed that the scores of "quality of care delivery" subscale in the modified ATHCTS and those of "expertise" subscale in the modified RIPLS declined significantly in the first-year students. Consequently, IPE programs may be introduced early in the undergraduate curriculum to prevent stereotyped perceptions for IPE, and comprehensive IPE curricula may result in profound changes in attitudes among participating students.

Interleukin-17F gene polymorphism in patients with chronic immune thrombocytopenia.

INTRODUCTION: IL-17F is a novel inflammatory cytokine and plays an important role in some autoimmune diseases. We investigated the association between chronic ITP and the frequency of the single-nucleotide polymorphism rs763780 (7488T/C), which causes a His-to-Arg substitution at amino acid 161. PATIENTS AND METHODS: We examined 102 patients (men/women, 40/62; median age, 42) diagnosed with chronic ITP and 188 healthy controls (men/women, 78/110; median age, 38). Genotyping was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: Compared with the control group, patients with chronic ITP had a significantly lower frequency of the IL-17F 7488CC genotype (0% vs. 4.8%, P<0.05). The number of IL-17F 7488C alleles among the patients with chronic ITP was also significantly lower than in the control group (8.7% vs. 15.2% OR=0.48, 95%CI=0.27-0.84, P=0.016). Furthermore, patients with the IL-17F 7488TT genotype showed a severe thrombocytopenic state (platelet count<10×10(9) /L) at diagnosis than those with the IL-17F 7488TC genotype (20.9% vs. 0%, P=0.04). CONCLUSION: These findings suggest that the IL-17F 7488 T allele is significantly associated with the development of chronic ITP, suggesting a role for IL-17F in the pathogenesis of chronic ITP.

[Evaluation of mental stress tests among medical students based on salivary sample collected just before the national license examination].

We investigated salivary amylase (sAMY) and chromogranin A (sCgA) in students before the national license examination in order to investigate the relationship between stress biomarkers and the Profile of Mood States (POMS) psychological test. Fifty-one medical students that provided informed consent were tested for sAMY activity and sCgA concentration by means of the amylase monitor method (NIPRO) and an ELISA kit (Yanaihara), respectively. The POMS psychology test (shortened form) was purchased from Chiba Test Center, and all students fully answered the lifestyle questionnaires. Based on answers to the questionnaires, students were divided by mental burden into three groups: I all"; II "large"; and III "very large". Scores for "T-A", "D" and "A-H" on the POMS test were significantly higher in groups II and III when compared with group I. Mean TMD scores calculated from the 6 items on the POMS test increased significantly with mental burden. The mean levels and 95% confidence interval (CI) of sAMY activity in the 3 groups were as follows: I, 27.7 (95% CI: 13.7-41.7) KIU/L; II, 29.1(95% CI: 22.4-35.7) KIU/L; and III, 26.9 (95% CI: 15.2-38.6) KIU/L. Mean sCgA concentrations were: I, 4.4(95% CI: 0-9.4) pmol/mg; II, 4.3(95% CI: 2.0-6.7) pmol/mg; and III, 10.9 (95% CI: 6.8-15.0) pmol/mg. There were no significant differences between these mean levels. However, Spearman's rank-correlation coefficient analysis for "T-A", sAMY and sCgA showed a stronger correlation between "T-A" and sCgA than between "T-A" and sAMY (p < 0.05). In conclusion, sCgA was more useful biomarker to evaluate the psychological stress before the national license examination than sAMY.

[Practical side of teamwork-based training--practice and evaluation in Gunma University].

In Gunma University, the School of Health Sciences was integrated with the Junior College Department into the Faculty of Medicine in 1996. For faculty integration, one of the most fundamental aspects of education was set as interprofessional education (IPE) in this school. To enhance collaboration between health professionals and overcome the fragmented nature of specialized medicine, the school has developed a curriculum, fundamentally based on holistic medicine and interprofessional work (IPW). The original and distinctive IPE was first introduced to 3rd grade students in 1999. The mandatory IPE practice training curriculum, designated as IPE, with multi-disciplinary students following a simulation training approach, has been implemented continuously for over 10 years. The major advantage of the curriculum lies in the training program, "a simulated interprofessional training", where students work in groups and perform a series of activities, including group discussions, clinical training at facilities, general meetings, and reporting. To assess the efficacy of IPE, a questionnaire survey was conducted for 11 years from 1999/2009. Students were asked to complete a short questionnaire with 10 questions and 2 or 3 open ended questions at the end of each IPE module. This systemic assessment of achievement has been developed independent of those described elsewhere, revealing the efficacy of the curriculum from a team building point of view. In this article, we introduce the results of the questionnaire survey in 2009. We hope that this article help in the teamwork-based training of students aiming to be medical technologists.

Flow cytometric detection of human telomerase reverse transcriptase (hTERT) expression in a subpopulation of bone marrow cells.

Telomerase activity has been found in most common cancers, thus indicating that telomerase detection may be a useful marker in cancer diagnosis. The telomeric amplification protocol (TRAP) assay and RT-PCR are customarily used to detect telomerase activity and the expression of the associated genes in cells. However, these methods do not provide any information about telomerase activation at an individual cell level. To analyze cells separately, those cells have to be isolated by sometimes complicated method. The immunohistochemical detection of human telomerase reverse transcriptase (hTERT) is useful to detect telomerase positive cells in a background of non-cancerous cells. A method has been developed for the detection of intranuclear hTERT protein, in a subpopulation of hematopoietic cells, using concurrent staining of a cell surface antigen and multicolor flow cytometry. Only mouse monoclonal anti-hTERT antibody demonstrated the specific positivity in immunocytochemistry and immunofluorescent flow cytometry. Human leukemia and myeloma cell lines showed 100% positivity, whereas normal neutrophils showed 0% positivity. hTERT expression was analyzed in hematopoietic precursor cells of bone marrow samples using concurrent staining of surface CD34 antigen and intracellular hTERT protein and multi-parameter flow cytometry. CD34 positive cells demonstrated higher expression of hTERT than CD34 negative cells. A quick, easy and sensitive assay for determining the hTERT protein expression has been developed. Using this method and the multi-parameter nature of flow cytometry and its ability to identify cellular subpopulations will provide a better understanding of the mechanisms regarding the activation of telomerase.

Systematic inclusion of mandatory interprofessional education in health professions curricula at Gunma University: a report of student self-assessment in a nine-year implementation.

BACKGROUND: The mandatory interprofessional education programme at Gunma University was initiated in 1999. This paper is a statistical evaluation of the programme from 1999 to 2007. METHODS: A questionnaire of 10 items to assess the achievement levels of the programme, which was developed independently of other assessment systems published previously, was distributed, as well as two or three open-ended questions to be answered at the end of each annual module. A multivariate analysis of variance model was used, and the factor analysis of the responses was performed with varimax rotation. RESULTS: Over all, 1418 respondents of a possible 1629 students completed the survey, for a total response rate of 87.1%. Cronbach's alpha of 10 items was 0.793, revealing high internal consistency. Our original questionnaire was categorized into four subscales as follows: "Role and responsibilities", "Teamwork and collaboration", "Structure and function of training facilities", and "Professional identity". Students in the Department of Occupational Therapy reached a relatively lower level of achievement. In the replies to the open-ended questions, requests for the participation of the medical students were repeated throughout the evaluation period. CONCLUSION: The present four subscales measure "understanding", and may take into account the development of interprofessional education programmes with clinical training in various facilities. The content and quality of clinical training subjects may be remarkably dependent on training facilities, suggesting the importance of full consultation mechanisms in the local network with the relevant educational institutes for medicine, health care and welfare.

Clinical significance of regulatory T cells in patients with myelodysplastic syndrome.

OBJECTIVE: Foxp3(+) regulatory T cells (Tregs) play a central role in maintaining immune tolerance. Their expansion in malignant diseases leads to the suppression of host anti-tumour responses. In this study, we evaluated the clinical significance of Tregs in patients with myelodysplastic syndrome (MDS). PATIENTS AND METHODS: We analysed the number of CD4(+) CD25(+) Foxp3(+) Tregs using three-colour flow cytometry in the peripheral blood of 26 patients with MDS classified according to the World Health Organization classification method into four cases of refractory anaemia and refractory anaemia with ringed sideroblasts (RA/RARS), 15 cases of refractory cytopenia with multilineage dysplasia (RCMD), three cases of refractory anaemia with excess blast-1 (RAEB-1) and four cases of refractory anaemia with excess blast-2 (RAEB-2). Eighteen healthy volunteers were included as the control group. RESULTS: The mean absolute numbers of Tregs in the RA/RARS group (0.06 x 10(9)/L; 95% CI, 0.02-0.10 x 10(9)/L) and RAEB group (0.06 x 10(9)/L; 95% CI, 0.02-0.10 x 10(9)/L) were significantly higher than that of the control group (0.03 x 10(9)/L; 95% CI, 0.02-0.03 x 10(9)/L) (P < 0.05). However, in the RCMD group, there was no significant difference in the mean absolute number of Tregs (0.03 x 10(9)/L; 95% CI, 0.02-0.04 x 10(9)/L) compared with the control group. Regarding the mean level of the CD8/Foxp3 ratio, there were significant decreases in the RA/RARS group (2.8; 95% CI, 0.7-4.9; P < 0.01), RCMD group (3.4; 95% CI, 2.0-4.4; P < 0.001) and RAEB group (2.1; 95% CI, 1.7-2.5; P < 0.001) compared with the control group (6.1; 95% CI, 5.1-7.0). CONCLUSIONS: The expansion of natural CD4(+) Tregs may contribute to the suppression of CD8 through the Th1-mediated immune response in MDS. The low CD8/Foxp3 ratio is a characteristic feature in MDS. To determine whether the expansion of CD4(+) Tregs contributes to the progression of MDS subtypes into more aggressive subtypes, more MDS cases and further follow-up are required.

Clinical significance of neutrophil apoptosis in peripheral blood of patients with type 2 diabetes mellitus.

UNLABELLED: Although neutrophils are essential components of the natural immune system, they have also been implicated in the pathogenesis of tissue injuries. We assessed the clinical significance of neutrophil apoptosis in the peripheral blood of patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: The study included 52 patients with T2DM (30 men, 22 women). Control subjects were 16 healthy volunteers without diabetes (7 men, 9 women). Neutrophil apoptosis levels were measured active caspase-3 positive rate by flow cytometry. RESULTS: The mean rate of neutrophil apoptosis in patients with T2DM was 15.0% (95% confidence interval [CI]: 9.5% approximately 20.5%), while that in the control group was 5.8% (95% CI: 1.6% approximately 10.0%). There were significant negative correlations between neutrophil apoptosis rate and hemoglobin (Hb) A1c levels (r = -0.352, P < .01). The mean rate of neutrophil apoptosis in the patient group with the 3 major complications (diabetic retinopathy, nephropathy, and neuropathy) was 11.1% (95% CI: 5.5%-16.7%, n = 36) and that of another group without complications was 23.8% (95% CI: 11.4%-36.2%, n = 16). There was a significant difference between these 2 groups (P < .05). CONCLUSIONS: The neutrophil apoptosis rate in patients with T2DM was significantly correlated with HbA1C levels. The mean rate of neutrophil apoptosis in the patient group with 3 major diabetic complications remained lower than that in another patient group without complications. The inhibition of neutrophil apoptosis by chronic hyperglycemia is thought to promote tissue injury and to enhance the risk of microangiopathy.

High Th1/Th2 ratio in patients with multiple myeloma.

To determine the clinical significance of the T helper 1(Th1)/T helper 2 (Th2) ratio in multiple myeloma, the intracellular IFN-gamma and IL-4 were analyzed by flow cytometry in 56 patients with multiple myeloma. The mean Th1/Th2 ratio of cases in the initial diagnosis phase and the refractory phase were higher than that of the control group. The mean serum beta-2-microglobulin in the high Th1/Th2 subgroup was significantly higher than that in the normal Th1/Th2 subgroup (P < 0.05). In conclusion, the Th1/Th2 ratio was closely related to the disease status of multiple myeloma.

[Urinary 8-hydroxy-2'-deoxyguanosin (8-OHdG) in patients with chronic liver diseases].

Urinary 8-hydroxy-2'-deoxyguanosin(8-OHdG) has been reported as sensitive biomarker of oxidative DNA damage and also of oxidative stress. We measured the urinary 8-OHdG in patients with chronic liver diseases by competitive ELISA, and analyzed the relationship with clinical characteristics. Fifty patients (male/female: 22/28) with chronic liver disease were enrolled this study. The mean concentration of urinary 8-OHdG in healthy control and patients with liver cirrhosis, chronic hepatitis C, chronic hepatitis B, and autoimmune hepatitis were 10.40+/-3.14, 10.14+/-4.19, 11.79+/-5.58, 14.99+/-4.46, and 13.64+/-3.84 microg/gCr, respectively. There were no significant differences among the five group. The mean concentration of urinary 8-OHdG in inveterate drinker was significantly higher than that in non-drinker (16.67+/-4.29 vs. 11.19+/-4.80 microg/gCr, p<0.05). The smoking enhanced the elevation of urinary 8-OHdG in drinkers. In clinical characteristics, serum y-GTP, a marker of alcoholic liver disease, had significant positive correlation with urinary 8-OHdG on the drinker with chronic hepatitis. In addition, there was a positive correlation between serum ferritin levels and urinary 8-OHdG levels. Iron in the liver suggested oxidative damage of hepatocytes through the fenton reaction in patients with chronic liver disease. In conclusion, drinking and smoking induced liver damage by oxidative stress, and urinary 8-OHdG may be reliable marker of oxidative stress in patients with chronic liver disease.

Th1/Th2 cells in patients with multiple myeloma.

Multiple myeloma (MM) is a lymphoproliferative disorder that is characterized by a proliferation of clonal B cells in various stages of maturation that then infiltrate the bone marrow. MM has been reported to accompany various T cell abnormalities including quantitative and functional defects of CD4+ and CD8+ T cells. Recently, immunotherapy such as dendritic cell therapy, vaccination therapy, and anti-tumor antibody therapy, has been attempted in patients with MM. To develop more effective immunotherapy for patients with MM, further studies are required to identify the immunological abnormalities, especially in T cells, associated with MM. The T helper 1 (Th1) and T helper 2 (Th2) cells are characterized by distinct cytokine production patterns. The Th1 cells produce interferon gamma and interleukin-2 (IL-2), and are involved in cell-mediated immunity. The Th2 cells produce IL-4 and promote humoral immunity by stimulating antibody production, particularly IgE responses. Furthermore, Th1 and Th2 cells have been found to cross-regulate each other's development. The Th1/Th2 combination has an important role in immune response to many disorders including infection, autoimmune diseases, and malignancies. In this review, we report a Th1/Th2 imbalance in cases of MM, and discuss the relationship between T cell abnormalities and the pathology of MM.

High Th1/Th2 ratio in patients with chronic idiopathic thrombocytopenic purpura.

Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by increased platelet clearance because of antiplatelet antibodies. It was recently reported that the balance of T helper 1 (Th1) and T helper 2 (Th2) subsets has been implicated in the regulation of many immune responses. In this study, the intracellular interleukin-4 and interferon-gamma production in CD4+ T-lymphocytes activated by phorbol 12-myristate 13-acetate and ionomycin was assessed via flow cytometry in order to determine the clinical significance of the Th1/Th2 ratio in 42 patients with ITP. The study cohort included 28 untreated patients, seven postprednisolone therapy patients and seven postsplenectomy patients. The mean level of the Th1/Th2 ratio in the untreated group was 36.9 (95% CI 25.8-47.9), and significantly higher than in the control group (mean 12.8, 95% CI 9.5-16.1). The mean levels of the Th1/Th2 ratio in the postprednisolone therapy and postsplenectomy groups were 20.5 (95% CI 8.4-32.6) and 16.4 (95% CI 3.1-29.7), respectively, but were no significant differences as compared with control subjects. When untreated patients were divided into two subgroups by Th1/Th2 ratio, the mean level of platelet associated IgG in the high Th1/Th2 subgroup (higher than upper limit of control group) tended to be higher than in the normal Th1/Th2 subgroup. In conclusion, the high Th1/Th2 ratio was closely related to the etiology and disease status of chronic ITP.

Combination chemotherapy of ranimustine, doxorubicine, and dexamethasone for relapsing multiple myeloma--a pilot study.

Twenty patients with relapsing myeloma were treated with combination chemotherapy of ranimustine, doxorubicine, and dexamethasone (RAD) between July 1996 and March 2000. Of the 19 evaluable patients, 5 (26.3%) achieved partial response after the first round of RAD therapy and 10 (52.6%) achieved partial response after the second round of RAD therapy. Of 10 evaluable patients who had previously received high-dose dexamethasone therapy including VAD therapy, 2 (20%) achieved partial response after the first round of RAD therapy and 3 (30%) achieved partial response after the second round of RAD therapy. The median survival was 10.5 months and the progression-free survival was 9.3 months. Patients who responded to RAD therapy had a survival rate at 43 months of 59.3%. Toxicity and adverse events during RAD therapy were tolerable. This pilot study demonstrated that RAD therapy is useful for the treatment o frefractory myeloma.

Steroid-refractory chronic idiopathic thrombocytopenic purpura associated with hepatitis C virus infection.

OBJECTIVES: Hepatitis C virus infection has often been suggested as a possible cause of various kinds of autoimmune diseases. The aim of this study was to determine the relationship between chronic idiopathic thrombocytopenic purpura (ITP) and hepatitis C virus infection and to characterize the clinical features of anti-HCV antibody (HCVab) positive chronic ITP patients. SUBJECTS AND METHODS: We studied HCVab in 79 patients with chronic ITP (25 males, 54 females, mean age 42.3 yr, range 11-86 yr) using the third-generation ELISA method. RESULTS: HCVab was detected in 11 of the 79 patients (13.9%). Quantitative HCV-RNA studies showed a high serum concentration of HCV-RNA in these patients. The platelet counts in these 11 HCVab-positive patients (Group 1) were lower than in the 68 HCVab-negative patients (Group 2) [(2.6 +/- 0.9) versus (4.9 +/- 3.0) x 10(10)/L, respectively; p<0.02]. Significantly more patients in Group 1 required prednisolone therapy (10/11, 90.9%) than in Group 2 (31/68, 45.6%) (P < 0.005). The response rate to prednisolone treatment was significantly higher in Group 2 (19/31, 61.3%) than in Group 1(0/10, 0%) (P < 0.001). There was no difference in the response to splenectomy between Groups 1 (4/7, 57.1%) and 2 (3/5, 60%). CONCLUSION: Given these findings, we recommend that HCVab is measured upon diagnosis of chronic ITP, and that splenectomy is planned in patients with HCVab in the event that prednisolone treatment is ineffective.

Ribosome-lamella complex of leukemic cells in a patient with aggressive NK cell leukemia.

A 36-year-old male was admitted to the hospital with anemia and leukopenia. A bone marrow specimen revealed the proliferation of leukemic cells with flower-like nuclei observed in adult T-cell leukemia. The leukemic cells were positive for HLA-DR, CD2, CD7, and CD56. A diagnosis of aggressive NK cell leukemia was made, the patient was treated with induction chemotherapy and cord blood stem cell transplantation, and he is well now. Seen with electron microscopy, some leukemic cells had ribosome-lamella complexes (RLC). This is the first reported case of leukemic cells with flower-like nuclei seen with light microscopy and RLC seen with electron microscopy.