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The successful treatment of an elderly patient with primary central nervous system lymphoma is described. A 74-year-old Japanese man with left hemiplegia and consciousness disturbance presented in December 2001. His performance status was Grade 4. Computed tomography of the brain revealed a tumor in the right paraventricle. A biopsy of the brain confirmed the diagnosis of non-Hodgkin lymphoma (diffuse large, B cell type). Radiographic examinations did not detect any other lesions outside the brain. Primary central nervous system lymphoma was diagnosed. Chemotherapy was initiated in January 2002 using intravenous administration of methotrexate (600 mg/m2, 6-h infusion, day 1) combined with etoposide (25 mg/m2, continuous infusion, day 2–5), doxorubicin (5 mg/m2, continuous infusion, day 2–5), vincristine (0.2 mg/m2, continuous infusion, day 2–5), cyclophosphamide (350 mg/m2, 2-h infusion, day 6) and dexamethazone (6 mg/body, 1-h infusion, day 1–6), with intrathecal administration of methotrexate (15 mg/body, day 8) and prednisolone (10 mg/body, day 8). Four courses of chemotherapy were completed without severe toxicities, followed by whole-brain radiotherapy (25 Gy). Complete remission was achieved, and the patient became alert with normalized movement of the left extremities. Despite poor prognostic factors (old age, low performance status), the patient was successfully treated as such and was still in remission without neurotoxicity in May 2004. The combination of methotrexate-based chemotherapy and radiotherapy with appropriate dose modification may improve the outcome in elderly patients with this disease since supportive therapy; CHOP, a combination of cyclophosphamide, doxorubicin, vincristine and prednisolone; and solo radiotherapy are usually not effective. [ABSTRACT FROM AUTHOR]

Oligella urethralis and Trueperella bernardiae are rare causes of bacteremia. A 96-year-old female nursing home resident with diabetes presented with polymicrobial bloodstream infection comprising these organisms and obstructive urinary tract infection. O. urethralis identified from blood cultures was resistant to fluoroquinolones and non-fourth-generation cephalosporins. Cases must be accumulated to define the clinical features of these organisms for infection control., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

This study aimed to establish a standard treatment for disseminated extranodal large B-cell lymphoma, including intravascular large B-cell lymphoma (DEN-LBCL/IVL), and to validate the clinical diagnostic criteria we proposed. Between 2006 and 2016, 22 patients were enrolled in a clinical trial conducted by the Hokuriku Hematology Oncology Study Group. The first cycle of chemotherapy consisted of dose-reduced cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with delayed administration of rituximab. From the second to the sixth cycle, patients received conventional rituximab and CHOP therapy. The primary endpoint was overall survival (OS), while the secondary endpoints included the complete response (CR) rate and time to treatment failure (TTF). The results showed a CR rate of 73%, a median OS of 65 months, and a median TTF of 45 months. These findings indicate that patients with DEN-LBCL/IVL were effectively treated with our new chemoimmunotherapy regimen. Our clinical diagnostic criteria are useful for identifying patients who require early intervention., Competing Interests: YM received research grants from Kyowa Kirin Pharma, Astellas Pharma, Eisai Pharma, Asahi Kasei Pharma, Daiichi-Sankyo Pharma, Taisho Pharma, Takeda Pharma, Chugai Pharma, Teijin Pharma, and Japan Blood Product Organization outside the submitted work. The other authors have no conflicts of interest to declare., (2024, National Center for Global Health and Medicine.)

Objective: In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA)., Methods: In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann-Whitney U-test, the log-rank test, logistic regression analysis, and Cox proportional hazards models., Results: Overall, 752 patients with RA-associated LPD (RA-LPD) and 770 with sporadic LPD were included in the study. We observed significant differences in the clinicopathologic features between patients with RA-LPD and those with sporadic LPD. Histopathological analysis revealed a high frequency of LPD-associated immunosuppressive conditions. Furthermore, patients with RA-LPD were evaluated based on the antirheumatic drugs administered. The methotrexate (MTX) plus tacrolimus and MTX plus tumor necrosis factor inhibitor (TNFi) groups had different affected site frequencies and histologic subtypes than the MTX-only group. Moreover, MTX and TNFi may synergistically affect susceptibility to Epstein-Barr virus infection. In case of antirheumatic drugs administered after LPD onset, tocilizumab (TCZ)-only therapy was associated with lower frequency of regrowth after spontaneous regression than other regimens., Conclusion: Antirheumatic drugs administered before LPD onset may influence the clinicopathologic features of RA-LPD, with patterns changing over time. Furthermore, TCZ-only regimens are recommended after LPD onset., (© 2024 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

•Tracheostomy wound myiasis is rarely observed in unconscious and immobile patients.•Maggots in the vicinity of the tracheostomy site should be closely monitored.•Controlling myiasis in hospitals requires fly control and patient fluid management., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: Daily uric acid excretion (Eua) is an essential index for patients with gout/hyperuricaemia. We identified alternative indices most correlated with 24-hour uric acid clearance (Cua 24 h) and 24-hour Eua (Eua 24 h) using data from the reference interval of urinary clearance and excretion of urate study., Methods: The subjects were indoor workers aged 20-65 years who met the Clinical and Laboratory Standards Institute Guidelines C28-A3c. Alternative indices using spot urine were urine uric acid creatinine ratio, Cua-creatinine clearance ratio (Cua/Ccr), Eua-CCr ratio (Eua/Ccr), estimated Cua (eCua), and estimated Eua (eEua). eCua and eEua are the values obtained by multiplying Cua/Ccr and Eua/Ccr with the estimated glomerular filtration rate., Results: The final number of subjects analysed was 739. Among the indices using spot urine, eCua and eEua showed the highest correlation with Cua 24 h and Eua 24 h, respectively. Compared with Cua 60 min and Eua 60 min obtained from 60-min urine collection, eCua and eEua showed lower root means squared error, lower bias, and significantly higher accuracy of within 30% and within 15%., Conclusions: The newly proposed eCua and eEua may be appropriate from a practical perspective., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The prevalence of patients with hyperuricemia or gout is increasing worldwide. Hyperuricemia and gout are primarily attributed to genetic factors, along with lifestyle factors like consuming a purine-rich diet, alcohol and/or fructose intake, and physical activity. While numerous studies have reported various comorbidities linked to hyperuricemia or gout, the range of these associations is extensive. This review article focuses on the relationship between uric acid and thirteen specific domains: transporters, genetic factors, diet, lifestyle, gout, diabetes mellitus, metabolic syndrome, atherosclerosis, hypertension, kidney diseases, cardiovascular diseases, neurological diseases, and malignancies. The present article provides a comprehensive review of recent developments in these areas, compiled by experts from the Young Committee of the Japanese Society of Gout and Uric and Nucleic Acids. The consolidated summary serves to enhance the global comprehension of uric acid-related matters.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Objectives: Although approximately 40 years have passed since Japanese spotted fever (JSF) was first reported in Japan, its treatment has not yet been standardised. As in other rickettsial infections, tetracycline (TC) is the first-line treatment, but successful instances of fluoroquinolone (FQ) combination therapy in severe cases have been reported. However, the effectiveness of TC plus FQ combined treatment (TC+FQ) remains controversial. Therefore, the antipyretic effect of TC+FQ was evaluated in this study., Methods: A comprehensive search of published JSF case reports was conducted to extract individual patient data. In cases where it was possible to extract temperature data, after homogenising patient characteristics, time-dependent changes in fever type from the date of the first visit was evaluated for the TC and TC+FQ groups., Results: The primary search yielded 182 cases, with individual data evaluations resulting in a final analysis of 102 cases (84 in the TC group and 18 in the TC+FQ group) that included temperature data. The TC+FQ group had significantly lower body temperature compared with the TC group from Days 3 to 4., Conclusions: Although TC monotherapy for JSF can eventually result in defervescence, the duration of fever is longer compared with other rickettsial infections such as scrub typhus. The results suggest that the antipyretic effect of TC+FQ was more effective, with a potential shortening of the duration that patients suffer from febrile symptoms., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Amenamevir has been approved for the treatment of herpes zoster (HZ); however, its therapeutic efficacy against central nervous system (CNS) infection may be insufficient due to its low spinal fluid permeability. We herein report a case of aseptic meningitis in a 91-year-old Japanese man treated with amenamevir for HZ in the trigeminal nerve region. Several cases of CNS infection have been reported in patients receiving amenamevir treatment for HZ. Patients with CNS complications often have skin rashes near the trigeminal region. Thus, we should be alert for signs of CNS infection when administering amenamevir to patients with such rashes.

Fungal co-infections of coronavirus disease 2019 (COVID-19) are generally infrequent, but are more common among patients with hematological diseases or severe cases in the intensive care unit (ICU). As fungal infections often carry a high mortality rate, preventing their development is considered important for patients with COVID-19. Caspofungin covers Candida spp. and Aspergillus spp. as causative pathogens of fungal infections associated with COVID-19, and is known to have few side effects among antifungal drugs. Recent studies have shown that caspofungin is expected to inhibit the growth of severe acute respiratory syndrome coronavirus 2. In addition, the inhibitory effects of caspofungin on spleen tyrosine kinase-related intracellular signaling are anticipated to suppress the overproduction of proinflammatory cytokines and immune thrombosis, which are problems in severe COVID-19. Early use of caspofungin in patients with COVID-19 with hematological diseases or in the ICU may help prevent fungal infections and reduce severe cases in COVID-19 patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier Ltd. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 rapid antigen detection (RAD) test kits are widely used as primary screening test in Japan because rapid diagnosis of coronavirus disease 2019 (COVID-19) is critical for infection control. We report cases with RAD test false-positive results in a ward for patients with disabilities. RAD tests potentially evoke hospital operational risk. It is desirable that performing PCR test appropriately when patients admitted to a medical treatment ward with COVID-19 symptoms instead of RAD test., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Although spiral bacteria are uncommon, they cause bacteremia. We evaluated their characteristics, in particular, the time from the start of blood culture to the first report of a positive result to physicians, using the BACTEC blood culture system. In cases of spiral bacteremia, an extended treatment period should be considered., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Invasive trichosporonosis is a rare and lethal fungal infection that occurs in immunocompromised patients. Breakthrough trichosporonosis can occur in patients treated with echinocandins since Trichosporon spp. are resistant to these antifungal agents. We report a case of breakthrough Trichosporon asahii fungemia. A 62-year-old Japanese woman with relapsed follicular lymphoma was treated empirically with broad-spectrum antibiotics and micafungin due to an intermittent fever during reinduction chemotherapy. After four cycles of anti-cancer chemotherapy, she experienced a high neutropenic fever and T. asahii was subsequently detected from a blood culture. The patient was not given voriconazole due to the contraindication for use with carbamazepine, and she was successfully treated with fluconazole plus liposomal amphotericin B without any serious complications. The combined therapy of fluconazole and liposomal amphotericin B may therefore be useful in treating T. asahii fungemia, especially in patients receiving antiepileptic agents.

Background: Pneumococcal pneumonia is the most frequent form of pneumonia. We herein assessed the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in the prevention of pneumonia overall in rheumatoid arthritis (RA) patients at risk for infections. We hypothesized that PPSV23 vaccination is superior in preventing pneumococcal pneumonia compared with placebo in RA patients., Methods: A prospective, multicenter, double-blinded, randomized, placebo-controlled (1:1) trial was conducted across departments of rheumatology in Japanese National Hospital Organization hospitals. RA patients (n = 900) who had been treated with biological or immunosuppressive agents were randomly assigned PPSV23 or placebo (sodium chloride). The primary endpoints were the incidences of all-cause pneumonia and pneumococcal pneumonia. The secondary endpoint was death from pneumococcal pneumonia, all-cause pneumonia, or other causes. Cox regression models were used to estimate the risk of pneumonia overall for the placebo group compared with the vaccine group., Results: Seventeen (3.7%) of 464 patients in the vaccine group and 15 (3.4%) of 436 patients in the placebo group developed pneumonia. There was no difference in the rates of pneumonia between the two study groups. The overall rate of pneumonia was 21.8 per 1000 person-years for patients with RA. The presence of interstitial pneumonia (hazard ratio: 3.601, 95% confidence interval: 1.547-8.380) was associated with an increased risk of pneumonia in RA patients., Conclusion: PPSV23 does not prevent against pneumonia overall in RA patients at relative risk for infections. Our results also confirm that the presence of interstitial lung disease is associated with pneumonia in Japanese patients with RA., Trial Registration: UMIN-CTR UMIN000009566 . Registered 17 December 2012.

Aim: We examined the utility of the neutrophil CD64 level as a rapid and sensitive diagnostic marker for infections in febrile aged patients., Methods: The expression level of CD64 per neutrophil was quantitatively measured with flow cytometry using a QuantiBrite kit in samples from febrile (aged >65 years) patients. Information about the presence or absence of infectious disease was retrospectively obtained from each patient's medical record in which attending physicians were obliged to write down a tentative diagnosis after resolution of manifestations., Results: With receiver operating characteristic curve evaluation using the results, a CD64 level >2000 molecules per neutrophil was sensitive and specific for detecting infection. Among 102 patients suspected of having infection, 72 patients were diagnosed with infectious diseases, and 30 patients had non-infectious diseases. The sensitivity and specificity of determination of the neutrophil CD64 level were 88% and 63%, respectively. However, considering the high frequency of infections in elderly patients (71% in the present study), the post-test probability reached as high as 93%. The positive likelihood ratio was 2.4, and the negative likelihood ratio was 0.2., Conclusions: Considering the frequency of infectious diseases in elderly patients, determination of the neutrophil CD64 level helps detect infectious diseases., (© 2015 Japan Geriatrics Society.)

Introduction: Patients with rheumatoid arthritis (RA) treated with abatacept (ABT) are at increased risk for vaccine-preventable infections. The aim of the present study is to evaluate the humoral response to 23-valent pneumococcal polysaccharide (PPSV23) vaccination in RA patients receiving ABT., Methods: The immunogenicity study was nested within a randomized, double-blind placebo-controlled study, designed to evaluate the efficacy of the PPSV23. PPSV23 was given to 111 RA patients, who were classified into three groups: RA control (n = 35), methotrexate (MTX) alone (n = 55), and ABT (n = 21). Before and 4-6 weeks after vaccination, we measured the patients' concentrations of antibodies against pneumococcal serotypes 6B and 23F using an enzyme-linked immunosorbent assay and determined their antibody functionality using a multiplexed opsonophagocytic killing assay, reported as the opsonization index (OI)., Results: The pneumococcal serotype-specific IgG concentrations and OIs were both significantly increased in all treatment groups in response to PPSV23 vaccination. In the ABT group, the IgG responses for the 6B serotype were lower compared with those in the MTX alone or control groups, whereas the OI responses were similar to those in the other two groups. In a subgroup analysis, the pneumococcal serotype-specific IgG responses were significantly lower in both serotypes (6B and 23F) in the ABT/MTX group; however, the OI responses in the ABT group were not different from the control group. There was no association between the pneumococcal serotype-specific IgG and OI responses for the 6B serotype in patients receiving ABT in contrast to the control or MTX alone patients. No severe adverse effects were observed in any of the treatment groups., Conclusions: OI responses indicate antibody functionality rather than simply their amount, so the similarity of these measurements between all three groups suggests that RA patients receiving ABT still benefit from receiving the PPSV23 vaccination, even though they produce less IgG in response to it. The results suggest an influence of ABT on the humoral response to PPSV23 vaccination under MTX treatment; however, preserved opsonin responses are expected in RA patients treated with ABT plus MTX., Trial Registration: University Hospital Medical Information Network Clinical Trials Registry: UMIN000009566. Registered 12 December 2012.

Vaccination against Streptococcus pneumoniae is recommended for rheumatoid arthritis (RA) patients receiving immunosuppressive treatments. The objective of this study was to evaluate the humoral response to 23-valent pneumococcal polysaccharide vaccination (PPSV23) in RA patients receiving methotrexate (MTX) alone or in combination with a tumor necrosis factor inhibitor, golimumab (GOM).PPSV23 was given to 114 RA patients, who were classified into three groups: RA control (n = 35), MTX alone (n = 55), and GOM + MTX (n = 24). Before and 4 to 6 weeks after vaccination, concentrations of antibodies against pneumococcal serotypes 6B and 23F were measured using an enzyme-linked immunosorbent assay and antibody functionality was determined using a multiplexed opsonophagocytic killing assay, reported as the opsonization index (OI).The IgG concentrations and OIs were both significantly increased in all treatment groups in response to PPSV23 vaccination. In the GOM + MTX group, the IgG responses were lower than those in the MTX alone or control groups, whereas the OI responses were similar to those in the other 2 groups. Furthermore, discrepancies between the IgG and OI responses were found in GOM + MTX group. No severe adverse effect was observed in any treatment groups.OI responses indicate that antibody functionality rather than antibody quantity is important. The similarity of these measurements between all 3 groups suggests that RA patients receiving MTX + GOM still benefit from receiving the PPSV23 vaccination, even though they produce less IgG in response to it. These results can help clinicians to better schedule and evaluate pneumococcal vaccination for RA patients., Competing Interests: The authors have no conflicts of interest to disclose.

Introduction: In rheumatoid arthritis (RA) patients receiving immunosuppressive treatments, vaccination against Streptococcus pneumoniae is recommended. The objective of the study was to evaluate the effects of tacrolimus (TAC) on immune response following administration of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) in patients with established RA., Methods: Patients with RA (n = 133) were vaccinated with PPSV23. Patients were classified into TAC (n = 29), methotrexate (MTX) (n = 55), control (n = 35), and TAC/MTX (n = 14) treatment groups. We measured the concentrations of pneumococcal serotypes 6B and 23F by using an enzyme-linked immunosorbent assay and determined antibody functionality by using a multiplexed opsonophagocytic killing assay, reported as the opsonization index (OI), before and 4 to 6 weeks after vaccination. A positive antibody response was defined as at least a twofold increase in the IgG concentration or as at least a 10-fold increase in the OI., Results: IgG concentrations and OIs were significantly increased in all treatment groups after PPSV23 vaccination. The TAC treatment group appears to respond in a manner similar to that of the RA control group in terms of 6B and 23F serotype concentration and function. In contrast, the MTX group had the lowest immune response. Patients who received a combination of TAC and MTX (TAC/MTX) also had a diminished immune response compared with those who received TAC alone., Conclusions: TAC monotherapy does not appear to impair PPSV23 immunogenicity in patients with RA, whereas antibody production and function may be reduced when TAC is used with MTX. Thus, PPSV23 administration during ongoing TAC treatment should be encouraged for infection-prone TAC-treated patients with rheumatic diseases., Trial Registration: University Hospital Medical Information Network Clinical Trials Registry: UMIN000009566. Registered 12 December 2012.

Interstitial lung disease (ILD) has a heterogeneous clinical presentation and establishing prognosis for these patients is challenging. We investigated the clinical characteristics and outcome of patients with idiopathic interstitial pneumonias (IIPs) and patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). We conducted a multicenter prospective study on 104 patients diagnosed with IIPs and 29 patients diagnosed with CTD-ILD, which were newly diagnosed and treated with corticosteroids initially. We compared the clinical characteristics, high-resolution computed tomography (HRCT) imaging date, and outcomes. Cox proportional hazard regression analysis was used to identify variables with increased risk of death. Survival was analyzed according to the Kaplan-Meier method and was assessed with the log-rank test. Of 133 patients with IIPs (n = 104) or CTD-ILD (n = 29), 44 patients died during the follow-up period (mean: 1.6 ± 0.78 years). Patients with IIPs seemed to be associated with worse survival compared with those with CTD-ILD; however, this difference was not significant (log-rank test, P = 0.084). Significant predictors for mortality in patients with IIPs at baseline were lower for performance status and definite usual interstitial pattern (UIP) on HRCT. Patients with UIP experienced worse survival than those with non-UIP. A definite UIP on HRCT and lower baseline performance status have important prognostic implications in patients with IIPs.

Background/aims: The Japanese National Hospital Organization evidence-based medicine (EBM) Study group for Adverse effects of Corticosteroid therapy (J-NHOSAC) is a Japanese hospital-based cohort study investigating the safety of the initial use of glucocorticoids (GCs) in patients with newly diagnosed autoimmune diseases. Using the J-NHOSAC registry, the purpose of this observational study is to analyse the rates, characteristics and associated risk factors of intracellular infections in patients with newly diagnosed autoimmune diseases who were initially treated with GCs., Methodology/principal Findings: A total 604 patients with newly diagnosed autoimmune diseases treated with GCs were enrolled in this registry between April 2007 and March 2009. Cox proportional-hazards regression was used to determine independent risk factors for serious intracellular infections with covariates including sex, age, co-morbidity, laboratory data, use of immunosuppressants and dose of GCs. Survival was analysed according to the Kaplan-Meier method and was assessed by the log-rank test. There were 127 serious infections, including 43 intracellular infections, during 1105.8 patient-years of follow-up. The 43 serious intracellular infections resulted in 8 deaths. After adjustment for covariates, diabetes (Odds ratio [OR]: 2.5, 95% confidence interval [95% CI] 1.1-5.9), lymphocytopenia (≦1000/μl, OR: 2.5, 95% CI 1.2-5.2) and use of high-dose (≧30 mg/day) GCs (OR: 2.4, 95% CI 1.1-5.3) increased the risk of intracellular infections. Survival curves showed lower intracellular infection-free survival rate in patients with diabetes, lymphocytopaenia and high-dose GCs treatments., Conclusions/significance: Patients with newly diagnosed autoimmune diseases were at high risk of developing intracellular infection during initial treatment with GCs. Our findings provide background data on the risk of intracellular infections of patients with autoimmune diseases. Clinicians showed remain vigilant for intracellular infections in patients with autoimmune diseases who are treated with GCs.

Monosodium urate (MSU) crystals are known to induce gouty arthritis, but also evoke specific cell immunity and work as an adjuvant by delivering several kinds of binding proteins, including idiotypic cancer vaccine peptides into dendritic cells. To investigate the potency of MSU crystals as a cancer vaccine carrier in vivo, this preclinical study examined whether intradermal injection of MSU crystals was safe for healthy adults. Subjects comprised 12 volunteers. Four different dose levels of MSU crystals were injected as follows: 2 μg (n = 3), 20 μg (n = 3), 200 μg (n = 3), or 2000 μg (n = 3). At 24 hours after administration, documented erythema was seen around the injection site in a dose-dependent manner, particularly in all adults with MSU dose ≥200 μg. However, redness was limited to the grade I level of the National Cancer Institute toxicity criteria. Serum uric acid levels did not show any change before and after injection. Moreover, neither gouty arthritis nor tophi developed in any volunteers, indicating that intradermal injection of MSU crystals did not induce systemic inflammation at the doses that evoked significant local inflammation. These findings suggest that intradermal injection of MSU crystals is fundamentally safe and should be made available for clinical trials using MSU-crystal-conjugated cancer vaccines.

We describe a rare case of secondary malignant fibrous histiocytoma (MFH) following Langerhans cell histiocytosis (LCH). A 23-year-old Japanese male exhibited systemic lymphadenopathy, multiple lung tumors, and osteolytic changes in bilateral iliac bones in 1989. A biopsy specimen from the left iliac bone revealed an infiltration of S-100 protein-positive histiocyte-like cells intermingled with eosinophils, which confirmed the diagnosis of eosinophilic granuloma, a type of LCH. Although the patient was treated with prednisolone initially, the disease did not respond well and progressed gradually over time. The patient subsequently received multiple courses of chemotherapy and immunosuppressive therapy with many kinds of anticancer agents for 6 years. He also received radiotherapy totaling 136.8 Gy for lung tumors and osteolytic lesions of the pelvis. In 1997, because of the LCH refractoriness, biopsy was performed again from the right inguinal lymph node. Microscopic examinations demonstrated a mixture of spindle-shaped cells and histiocyte-like cells, which appeared to be in a storiform pattern. The tumor cells were immunohistologically positive for CD68 and vimentin, but negative for CD1a and S-100 protein. Therefore, the patient was diagnosed with MFH. Although chemotherapy was continued, the patient died of pneumonia during the neutropenic period following chemotherapy. Autopsy revealed systemic invasion of MFH and dissemination of mucormycosis. LCH was not detected histologically in any tissues.

Monosodium urate (MSU) crystals have been reported to evoke specific cell immunity and to work as an adjuvant in a mouse model. The crystals also have another unique characteristic to bind with positively charged proteins, which could help to deliver some antigens into human dendritic cells (DC). We focused on the application of MSU crystals as not only an adjuvant but also as a carrier of positively charged antigenic protein to induce human cytotoxic T cells (CTL) efficiently in vitro. We selected human leukocyte antigen (HLA)-A2 expressing the multiple myeloma IM-9 cell line and its product idiotype (Id) protein as one of the best pairs of target cells and positively charged tumor-specific antigen, respectively. Following the sensitization of DC derived from HLA-A2-positive volunteers pulsed with tumor-specific monoclonal immunoglobulin G-Fab fragments (IM-9 Fab) attached to MSU crystals, the DC-stimulated CD8(+) T cells killed significantly more target cells (40.1 +/- 1.7%) than those stimulated by DC pulsed with MSU crystals alone (6.2 +/- 8.6%, P < 0.01) or IM-9 Fab alone (4.7 +/- 8.1%, P < 0.01). These cytotoxic effects of the DC-stimulated CD8(+) cells were reduced when MSU crystals were precoated with fetal bovine serum. In addition, we confirmed that MSU crystals facilitated human DC to express the maturation marker, CD83 and deliver (Fab')(2), attaching to the crystals by flow cytometer analysis. MSU crystals have distinct advantages of a protein carrier binding with positively charged proteins and delivering antigenic protein into DC, as well as an adjuvant promoting DC maturation and inducing CTL.

Hyperuricemia caused secondly from acquired disorders which affect production or excretion of uric acid is defined as secondary hyperuricemia. Many conditions are associated with this type of hyperuricemia and are classified into three types according to the underlying pathophysiology, including accelerated purine nucleotide degradation, ATP breakdown and purine de novo biosynthesis as overproductive type, use of drugs affecting renal urate handling and renal insufficiency as underexcretion type, or overintake of alcohol or fructose as mixed type. Determining uric acid clearance and urate excretion is important for pointing out original disorder; however, sometimes the result from correcting causal factor should be waited for to fix up a final diagnosis. Anti-hyperuricemia agents are used according to the pathophysiology.

Complete elimination of the plasma cell dyscrasia is a rational therapeutic goal, as intercepting supply of precursor protein is a necessary condition for a major regression of amyloid deposits. High-dose melphalan with autologous stem cell transplantation has shown the ability to induce complete hematological response (HR) along with recovery of organ dysfunction. However, the rate of HR with this treatment rarely exceeds 40%. We describe here the first known case of successful reduced intensity allogeneic stem cell transplantation (RIST) for a patient with primary amyloidosis complicated with nephrotic syndrome but without cardiac disease, who had obtained only partial HR by high-dose melphalan with autologous stem cell transplantation. RIST may be feasible and be capable of achieving complete HR along with recovery from nephrotic syndrome with acceptable toxicity.

Two antibiotics recommended by the guideline of Infectious Diseases Society of America (IDSA) were selected for treatment of febrile neutropenia, and these paired antibiotics were changed periodically three times. The clinical efficacy of each antibiotic was retrospectively evaluated at the end of the final period. There was no significant difference about efficacy rate between two kinds of antibiotics in the same sequential period. However, the efficacy rate has been rising and febrile duration has been shortening by degrees. Only a few drug resistant bacteria were recognized by the surveillance culture during antibiotic cycling. Recently, antibiotic cycling therapy has attracted attention especially in the ICU. However, a clinical study of treatment for febrile neutropenia has not been reported. Our trial suggests that cycling therapy may be useful for febrile neutropenia. However, Some deviation in the patients characteristics of each period may affect the result. It seems that further examination is necessary about usefullness of the cycling therapy for febrile neutropenia.