Effectiveness and safety of adalimumab in Japanese patients with rheumatoid arthritis: retrospective analyses of data collected during the first year of adalimumab treatment in routine clinical practice (HARMONY study)

We retrospectively investigated the ability of adalimumab (ADA) to reduce disease activity, improve physical function, and retard the progression of structural damage in 167 patients with rheumatoid arthritis. Clinical and functional outcomes were compared between patients with or without prior biologic treatment and those with or without concomitant methotrexate (MTX) treatment. At week 52, 38.3% achieved clinical remission: 42.4 and 28.6% of patients achieved remission in those without and with previous biologics, respectively, while 42.7 and 12.5% of patients achieved remission in those with and without concomitant MTX, respectively. ADA treatment significantly reduced the rate of radiographic progression from 27.1 ± 46.0 (median 13.6; 25th-75th percentiles 8.3 to 28.9) at baseline to 0.8 ± 5.0 (median 0.0; 25th-75th percentiles -0.9 to 2.0) at week 52 (P < 0.0001). Radiographic progression was absent in 59.8% of patients. Sixty adverse events (34.21/100 patient-years) were reported, 16 of which were serious (9.12/100 patient-years). ADA therapy is highly effective for reducing disease activity, improving physical function, and limiting radiographic progression. It is generally safe and well tolerated by Japanese RA patients in routine clinical practice.     

A case of catastrophic antiphospholipid antibody syndrome complicated with systemic lupus erythematosus, double positive for anti-cardiolipin/β2 glycoprotein?I and anti-phosphatidylserine/prothrombin autoantibodies

A 16-year-old male with severe thrombocytopenia and progressive multiple organ infarctions was diagnosed as having catastrophic antiphospholipid syndrome (CAPS) complicated with systemic lupus erythematosus, and was successfully treated with combination of anticoagulants, corticosteroids, plasma exchange, and intravenous cyclophosphamide. Antibodies to phosphatidylserine/prothrombin (PS/PT) complex and cardiolipin (CL)/β(2)-glycoprotein?I (β(2)GPI) were simultaneously detected, indicating that the different pathways of both PS/PT and CL/β(2)GPI might be associated with the radical manifestation of CAPS.     

Prognosis of pneumocystis pneumonia complicated in patients with rheumatoid arthritis (RA) and non-RA rheumatic diseases

Clinical presentation of pneumocystis pneumonia (PCP) during immunosuppressive therapy for rheumatic diseases was compared between patients with rheumatoid arthritis (RA; n = 7) and those without RA (non-RA; n = 12) based on a chart review. Both RA and non-RA patients with PCP were treated with methotrexate (n = 7) combined with steroids (n = 6) and/or biologics (n = 4). RA-PCP patients were found to have a higher mortality rate than non-RA-PCP patients (3/7 vs. 0/12, respectively; p?=?0.036) due to a later exacerbation of interstitial pneumonia and a higher presentation rate of diffuse pulmonary lesions (4/7 vs. 1/12, respectively; p?=?0.036) despite lower mean levels of serum beta-D: -glucan (314?±?214 vs. 1139?±?1114?pg/ml, respectively; p?=?0.02) that suggested a lower burden of Pneumocystis jirovecii. In conclusion, PCP in RA patients with existing pulmonary lesions may trigger subsequent progression to lethal interstitial pneumonia.     

Association of 29C>T polymorphism in the transforming growth factor‐β1 gene with lean body mass in community‐dwelling Japanese population

Aim: Sarcopenia is the significant degenerative loss of skeletal muscle mass and strength associated with aging, and it is one of the components of frailty. We previously reported an association between the 29C>T polymorphism in the transforming growth factor‐β1 gene (rs1800470) and the prevalence of vertebral fractures in subjects with postmenopausal osteoporosis. The association was not attributable to bone mineral density, which suggests that polymorphism influences some aspects of bone quality that affects strength and/or frailty rather than bone strength itself. Thus, we examined the relationship between genetic polymorphism and lean body mass in a Japanese population. Methods: A total of 479 adults comprising 143 men and 336 women, age 23 to 85 years, participated in the present study. Fat‐free mass was measured by dual energy X‐ray absorptiometry, and the relative skeletal muscle index was calculated as the ratio of appendicular (sum of arms and legs) fat‐free mass to the square of height. Results: Total, leg, and appendicular fat‐free mass as well as the relative skeletal muscle index were significantly lower in male subjects with CT/TT genotypes compared to those with CC genotype. Female subjects did not show any genotype‐dependent differences when analyzed as a group, but when those without menstruation (postmenopausal women) were analyzed, arm fat‐free mass was significantly lower in the CT/TT genotypes than in the CC genotype. Conclusions: T allele of the 29C>T polymorphism in the transforming growth factor‐β1 gene might be a risk factor of sarcopenia in a Japanese population. Geriatr Gerontol Int 2012; 12: 292–297.     

Characteristics of urinary and serum soluble Klotho protein in patients with different degrees of chronic kidney disease

Background

Klotho is a single-pass transmembrane protein, which appears to be implicated in aging. The purpose of the present study was to characterize the relationship between the soluble Klotho level and renal function in patients with various degrees of chronic kidney disease (CKD).

Methods

The levels of soluble Klotho in the serum and urine obtained from one hundred thirty-one CKD patients were determined by a sandwich enzyme-linked immunosorbent assay system.

Results

The amount of urinary excreted Klotho during the 24 hr period ranged from 1.6 to 5178 ng/day (median 427 ng/day; interquartile range [IR] 56.8-1293.1), and the serum Klotho concentration ranged from 163.9 to 2123.7 pg/ml (median 759.7 pg/ml; IR 579.5-1069.1). The estimated glomerular filtration rate (eGFR) was significantly correlated with the log-transformed values of the amount of 24 hr urinary excreted Klotho (r?=?0.407, p?<?0.01) and the serum Klotho levels (r?=?0.232, p?<?0.01). However, a stepwise multiple regression analysis identified eGFR to be a variable independently associated only with the log-transformed value of the amount of 24-hr urinary excreted Klotho but not with the log-transformed serum Klotho concentration. Despite the strong correlation between random urine protein-to-creatinine ratio and the 24 hr urinary protein excretion (r?=?0.834, p?<?0.01), a moderate linear association was observed between the log-transformed value of the amount of 24 hr urinary excreted Klotho and that of the urinary Klotho-to-creatinine ratio (Klotho/Cr) in random urine specimens (r?=?0.726, p?<?0.01).

Conclusions

The amount of urinary Klotho, rather than the serum Klotho levels, should be linked to the magnitude of the functioning nephrons in CKD patients. The use of random urine Klotho/Cr as a surrogate for the amount of 24-hr urinary excreted Klotho needs to be evaluated more carefully.

     

Simple organocatalyst component system for asymmetric hetero Diels–Alder reaction of isatins with enones

A simple two catalyst component system consisting of primary β-amino alcohols as a catalyst and amino acids as a co-catalyst put together works as an efficient organocatalyst system in the hetero Diels–Alder reaction of isatins with enones to afford the chiral spirooxindole–tetrahydropyranones in good chemical yields and stereoselectivities (up to 86%, up to 85 : 15 dr., up to 95% ee).

A simple two catalysts component system of β-amino alcohols (catalyst) and amino acids (co-catalyst) works as an efficient organocatalysts in hetero Diels–Alder reaction of isatins with enones to afford chiral spirooxindole-tetrahydropyranones.     

Synthesis and investigation of sulfonated poly(p-phenylene)-based ionomers with precisely controlled ion exchange capacity for use as polymer electrolyte membranes

To achieve precise control of sulfonated polymer structures, a series of poly(p-phenylene)-based ionomers with well-controlled ion exchange capacities (IECs) were synthesised via a three-step technique: (1) preceding sulfonation of the monomer with a protecting group, (2) nickel(0) catalysed coupling polymerisation, and (3) cleavage of the protecting group of the polymers. 2,2-Dimethylpropyl-4-[4-(2,5-dichlorobenzoyl)phenoxy]benzenesulfonate (NS-DPBP) was synthesised as the preceding sulfonated monomer by treatment with chlorosulfuric acid and neopentyl alcohol. NS-DPBP was readily soluble in various organic solvents and stable during the nickel(0) catalysed coupling reaction. Sulfonated poly(4-phenoxybenzoyl-1,4-phenylene) (S-PPBP) homopolymer and seven types of random copolymers (S-PPBP-co-PPBP) with different IECs were obtained by varying the stoichiometry of NS-DPBP. The IECs and weight average molecular weights (M_ws) of ionomers were in the range of 0.41–2.84 meq. g⁻¹ and 143 000–465 000 g mol⁻¹, respectively. The water uptake, proton conductivities, and water diffusion properties of ionomers exhibited a strong IEC dependence. Upon increasing the IEC of S-PPBP-co-PPBPs from 0.86 to 2.40 meq. g⁻¹, the conductivities increased from 6.9 × 10⁻⁶ S cm⁻¹ to 1.8 × 10⁻¹ S cm⁻¹ at 90% RH. S-PPBP and S-PPBP-co-PPBP (4 : 1) with IEC values >2.40 meq. g⁻¹ exhibited fast water diffusion (1.6 × 10⁻¹¹ to 8.0 × 10⁻¹⁰ m² s⁻¹), and were comparable to commercial perfluorosulfuric acid polymers. When fully hydrated, the maximum power density and the limiting current density of membrane electrode assemblies (MEAs) prepared with S-PPBP-co-PPBP (4 : 1) were 712 mW cm⁻² and 1840 mA cm⁻², respectively.

Poly(p-phenylene)-based sulfonated polymers with well-controlled IECs were synthesized via a three-step procedure including preceding sulfonation of precursor monomers.     

The association between fecal incontinence and sexual activity and function in women attending a tertiary referral center

Introduction and hypothesis

To determine whether fecal incontinence (FI) is associated with sexual activity and to compare sexual function in women with and without FI.

Methods

We conducted a retrospective chart review of all new patients seen in an academic urogynecology clinic. Women who reported fecal incontinence, as defined by loss of fecal material on the Wexner scale, were compared with those without fecal incontinence. We compared sexual activity and Pelvic Organ Prolapse Incontinence Sexual Questionnaire-12 (PISQ-12) scores between groups.

Results

In our population of women with pelvic floor disorder, 588 women reported FI compared with 527 who did not. On multivariate analysis, FI was not associated with sexual activity status, but was associated with worsened PISQ-12 scores (p?<?0.001). PISQ-12 item analysis found that women with FI reported more dyspareunia, fear, and avoidance of sexual activity with greater partner problems (all p <0.05) than women without FI.

Conclusions

Women with FI were as likely to engage in sexual relations as women without FI; however, sexually active women with FI had poorer sexual function than those without FI.