The side‐effects and efficacy of leflunomide in Japanese patients with rheumatoid arthritis

Aims: To investigate the efficacy and safety of leflunomide, including the side‐effects, we assessed 84 rheumatoid arthritis (RA) patients who received leflunomide treatment. Methods: We analyzed the C‐reactive protein (CRP), white blood cell count (WBC), KL‐6, and visual analogue scale (VAS) scores, modified Stanford Health Assessment Questionnaire (MHAQ) score, American Rheumatism Association score (ACR20 and ACR50) within a time course after treatment with leflunomide. We treated 84 RA patients, 12 male and 72 female from 28 to 81‐years‐old, with an average age of 63.5 years. The patients were divided into three groups: a group consisting of 38 patients who received 100 mg/day of leflunomide for 3 days followed by 20 mg/day thereafter; a second group of 11 patients who received a no‐loading dose of 10 mg/day; and a third group of 35 patients who received a no loading dose of 20 mg/day. Results: The 50% decrease of CRP seen in 2 weeks was 52% of the total of 84 patients. The WBC score did not change significantly after the medication was given. The KL‐6 score did not change significantly, either. The VAS pain score improved 4 weeks later, and then further improved 8 weeks later. Therefore, RA patients using leflunomide obtained pain relief 4 weeks after commencing medication. The MHAQ score did not change significantly until 8 weeks after the patients started the medication. ACR20 was 62% and ACR50 was 38% at 8 weeks after treatment. The side‐effects of leflunomide observed in our patients were rash, respiratory infection, diarrhea, nausea, alopecia, muscle pain, headache, dizziness and general fatigue. Twenty‐three out of 84 patients experienced side‐effects (27%), and 48/84 (57%) experienced withdrawal. In our hospital, there were no patients who developed severe interstitial pneumonia (IP) or who died after taking leflunomide; however, the incidence of side‐effects of the 100 mg/day loading dose (42.1%) was 2.5 times higher than in the patients who received 20 mg/day (17.1%) of a no‐loading dose. Conclusion: Because of this, it is possible that a 100 mg/day loading dose is a relatively high risk dose in terms of causing side‐effects, especially for severely ill RA patients with a high CRP level.     

Association of mannose‐binding lectin gene polymorphisms with Kawasaki disease in the Japanese

Objective: Kawasaki disease (KD) is a systemic vasculitis in childhood; its etiology is unknown. The possibility that KD is an infectious disease has been discussed and investigated for decades, in light of the implication that infections are involved in the pathogenesis of KD. Young children rely on their innate immune system for protection against virus and micro‐organisms. Human mannose binding lectin (MBL) is a C‐type serum lectin synthesized by the liver as an acute phase protein and it plays an important role in the innate immune system. Here, we investigate the relationship between the MBL gene polymorphisms and the occurrence of KD in the Japanese population. Method: The frequencies of the genotypes, defined as mutations in codons 52, 54 and 57, and the functional promoter variants of the MBL were determined in 45 patients with KD. Results: The MBL codon‐54 polymorphism frequency of heterozygote (GGC/GAC) and promoter variants were significantly higher in the KD group than that in the control group (P < 0.05). Neither group showed codon 52 nor 57 polymorphisms. Conclusion: It is possible that mutations of the MBL gene might be related to the trigger of the pathogenesis of Kawasaki disease.     

JK null alleles identified from Japanese individuals with Jk(a−b−) phenotype

The Kidd blood group system consists of three common phenotypes: Jk(a+b?), Jk(a?b+) and Jk(a+b+), and one rare phenotype, Jk(a?b?). Jk^a/Jk^b polymorphism is associated with c.838G>A (p.Asp280Asn) in exon 9 of the JK (SLC14A1) gene, and the corresponding alleles are named JK*01 and JK*02. The rare phenotype Jk(a?b?) was first found in a Filipina of Spanish and Chinese ancestry, and to date, several JK null alleles responsible for the Jk(a?b?) phenotype have been reported. We report seven novel JK null alleles, 4 with a JK*01 background and 3 with a JK*02 background, identified from Jk(a?b?) Japanese.     

Association of Japanese dietary pattern with serum adiponectin concentration in Japanese adult men

Background and aimsAlthough previous studies suggest that the traditional Japanese dietary pattern is independently associated with a low cardiovascular disease mortality risk, the mechanisms mediating or linking this association are not well understood. Adiponectin has emerged as a valuable biomarker for cardiovascular diseases. The aim of present study was to evaluate whether dietary patterns are associated with serum adiponectin concentration in Japanese adult men.Methods and resultsWe designed a cross-sectional study of 702 men (median [interquartile range] age, 44.5 [37.8–54.2] years) living in Japan. Dietary consumption was assessed via a 75-item food frequency questionnaire. We used principal-components analysis to derive 3 major dietary patterns-“Japanese”, “sweets-fruits” and, “Izakaya (Japanese Pub)”- from 39 food groups. Serum adiponectin concentration was measured by using a specific sandwich enzyme-linked immunosorbent assay. After adjustment for potential confounders, the geometric mean (95% confidence interval) for log-transformed adiponectin concentration associated with “Japanese” dietary pattern factor score tertiles were 5.24 (4.84–5.69) for the lowest tertile, 5.82 (5.39–6.29) for the middle tertile, and 5.95 (5.47–6.46) for the highest tertile (P for trend <0.01). In contrast, a significant inverse association was found between the “Izakaya” pattern factor score tertiles and adiponectin concentration (P for trend = 0.03).ConclusionsGreater adherence to the “Japanese” dietary pattern was independently associated to a higher serum adiponectin concentration in Japanese adult men. This finding supports the hypothesis that the traditional Japanese diet may have a potentially beneficial effect on adiponectin concentrations. A long-term prospective study or randomized trials are required to clarify this causality.     

Japanese American Caregivers of Individuals with Dementia

Abstract

As the population of the United States continues to live longer than in previous years, a larger number of older adults are being diagnosed with dementia or other memory-related conditions. The individuals who experience a tremendous amount of stress and burden are the caregivers for the individual with dementia. The majority of the dementia caregiver research has been conducted on Caucasian caregivers, and to a lesser extent on Latino and African American caregivers. However, there is a paucity of research based on Japanese American care-givers. An understanding of how Japanese culture often affects Japanese American caregivers will assist clinicians in providing culturally competent health care to this group of caregivers. The authors provide an overview of the Japanese caregiver literature, followed by a discussion of traditional Japanese cultural values as they apply to a case example that illustrates the interaction of Japanese cultural values and dementia care-giving.     

Association of Japanese cedar pollinosis and sensitization with HLA-DPB1 in the Japanese adolescent

Background

Allergic rhinitis (AR) is a heterogeneous disorder that significantly affects daily activity, work productivity, sleep, learning, and quality of life in all generations. Japanese cedar (JC) pollen is the most common allergen responsible for the development of AR in Japan. AR caused by JC pollen is considered to be a multifactorial inheritance disease that is caused by both environmental and genetic factors. The aim of this study was to investigate whether Human Leukocyte Antigen-DPB1 (HLA-DPB1) is associated with JC sensitization/pollinosis.

Efficacy and safety of sitagliptin in Japanese patients with type 2 diabetes switched from glinides

Aims/Introduction

The efficacy and safety of sitagliptin, a dipeptidyl peptidase (DPP)‐4 inhibitor, were compared with those of glinides in Japanese patients with type 2 diabetes.

Materials and Methods

The participants were 82 patients with type 2 diabetes (glycated hemoglobin [HbA1c] ≥6.0% and <10%) under treatment with glinides for glucose control. The participants were randomly assigned to a group (n = 44) receiving continuous treatment with glinides and a group (n = 38) switched to sitagliptin. Patients were followed for 12 weeks to evaluate glucose control. A meal tolerance test was carried out in weeks 0 and 12 to examine the pancreatic secretory response to postprandial hyperglycemia.

Results

The changes in HbA1c from week 0 to week 12 were −0.25 and −0.05% in the sitagliptin and glinide groups, respectively, with a significant improvement with sitagliptin. The differences in fasting plasma glucose (FPG), glycoalbumin and 1,5‐anhydroglucitol between the two groups were 14.2 mg/dL, 0.7% and 1.7 μg/mL, respectively, showing significant improvements with sitagliptin. In the meal tolerance test, glucose at 0 min was lower in the sitagliptin group; however, there were no differences in glucose elevation at 30 and 60 min compared with 0 min. Plasma insulin and glucagon secretion at week 12 were significantly lower than at baseline in the sitagliptin group. Adverse events including hypoglycemia did not differ between the groups.

Conclusions

FPG decreased and glucose control improved in patients who switched from glinides to sitagliptin. Sitagliptin decreased secretion of insulin and glucagon in a meal tolerance test compared with glinides, whereas the agents showed similar inhibition of postprandial hyperglycemia. This trial was registered with UMIN (UMIN‐CTR no. 000003479).