Efficacy on the risk of vertebral fracture with administration of once-weekly 17.5 mg risedronate in Japanese patients of established osteoporosis with prevalent vertebral fractures: a 156-week longitudinal observational study in daily practice.

Currently, the only available evidence for the efficacy of once-weekly 17.5 mg risedronate in preventing vertebral fractures was obtained in a 48-week study in Japan. We performed a 156-week prospective, longitudinal, observational study to determine the efficacy of the 17.5 mg risedronate in preventing vertebral fractures. We included Japanese patients with established osteoporosis who were older than 50 years and had radiographically confirmed vertebral fractures. The primary endpoint was the incidence of vertebral fractures every 24 weeks, with the final interval spanning 36 weeks. We also calculated the change in bone mineral density of the lumbar spine (L2-4 BMD) and urinary N-telopeptide of type I collagen (u-NTX), and assessed the incidence of adverse drug reactions and the drug adherence rate. Data from 241 patients were available for analysis of vertebral fracture prevention. The incidence rate of vertebral fractures decreased in a time-dependent manner (P = 0.0006; Poisson regression analysis). The risk ratio (fracture incidence per 100 person-years in the final 36 weeks versus that in the first 24 weeks) was 0.21 (95 % confidence interval 0.08-0.55). Compared to baseline values, L2-4 BMD increased by 6.41 % at 156 weeks, while u-NTX decreased by 36 % at 24 weeks and was maintained thereafter (P < 0.0001). The incidence rate of adverse drug reactions was 9.18 %. Drug adherence rates assessed every 4 weeks were over 90 %. Our results indicate that 156 weeks of treatment with once-weekly 17.5 mg risedronate effectively reduced the risk of vertebral fracture in Japanese patients with established osteoporosis older than 50 years.

[Usefulness of Polyethylene-Glycol Precipitation As a Screening Method for Macroprolactinemia].

Macroprolactin is mostly a complex of monomeric prolactin (PRL) with IgG and considered to be biological inactive. Its presence commonly leads to diagnostic confusion and misdiagnosis. Polyethylene-glycol (PEG) precipitation method is widely used for a screening of macroprolactinemia. We applied PEG precipi- tation method for 200 samples which was ordered test of PRL. The PRL recovery was 65.0±11.2% (mean ±SD). In our data, PRL recovery less than 42.5% (mean-2SD) indicates the presence of macroprolactin. The prevalence of macroprolactinemia was 4.5%(9/197) in total samples and 9.5%(2/21) in hyperprolac- tinemia. Our result indicates the need for PEG screening for macroprolactinemia to avoid misdiagnosis. [Short Communication].

[Cross-reactivity evaluation of improved estradiol (E2) assay reagent based on chemiluminescent enzyme immunoassay].

We evaluated the performance of a newly-improved estradiol(E2) assay reagent (NEW LP-E2-N), which replaces murine monoclonal antibody in the present reagent (LP-E2-N) with sheep monoclonal antibody, since we had experienced discrepant E2 assay results between LP-E2-N and other commercially available E2 assay kits. Several examinations with the new assay reagent indicated a good performance in terms of the limit of quantity, reproducibility (within-run and between-day), dilution linearity, and influence of blood components except hemoglobin. Using analogues and/or metabolites of E2, low or no cross-reactivity has been shown in NEW LP-E2-N: 0.26% with 25 ng/mL of estrone (El), 0.14% with 100 ng/mL of estradiol-3-sulfate, 0.02% with 200 ng/mL of 17α-ethynylestradiol, and less than 0.001% with 100 ng/mL of estriol(E3), estra-17-glucuronide, and estramustine, respectively. Although discrepant results between NEW LP-E2-N and LP-E2-N were observed in 12 samples, including 9 cases under oral hormone therapy, data from these samples were similar to those using 2 commercially available E2 assay kits, Architect and Eclusys, suggesting that the NEW LP E2-N shows adequate clinical efficacy. A correlation study was performed with LP E2-N, Architect, and Eclusys using 149 serum samples obtained from patients and healthy volunteers, and the correlation results were as follows: r = 0.831, y = 0.98x + 40.6 against LP-E2-N, r = 0.991, y = 1.08x + 12.4 against Architect, r = 0.995, y = 0.80x - 3.7 against Eclusys. In conclusion, the NEW LP-E2-N reagent displayed a relatively favorable kit performance except for in the elevation of assay results with hemoglobin, as well as a low cross-reactivity with E2 analogues and/or metabolites.

[A case of Burkitt lymphoma with multifocal bone invasion].

A 12-year-old boy admitted to a local hospital with fever, migratory arthralgia, and periosteal reaction on X Ray. He was transferred to our hospital because magnetic resonance imaging scan of his whole body showed multiple abnormal signals in bones. Laboratory findings on admission showed the increased erythrocyte sedimentation rate, uric acid, lactate dehydrogenase, alkaline phosphatase, C-reactive protein, immunoglobulin G, hemolytic complement activity and soluble interleukin-2 receptor. Peripheral blood and bone marrow examination did not show any abnormality. The clinical appearance of his condition suggested the diagnosis of chronic recurrent multifocal osteomyelitis (CRMO). He was treated with steroid, however his fever and bone pain continued. A bone and bone marrow biopsy was performed and the results of histopathology showed precursor-B acute leukemia/lymphoma. His bone pain relapsed after the chemotherapy for ALL. Finally, blast cells resembling L3 morphology were detected in the peripheral blood. The reevaluated bone marrow was predominantly replaced with Burkitt like lymphoblasts. He was diagnosed with Burkitt lymphoma by further specific examination.

[Report of immunoassay control surveys conducted in the past 30 years by the Subcommittee for Radioisotope in vitro Test, the Medical Science and Pharmaceutical Committee, and the Japan Radioisotope Association].

Immunoassay control surveys, were conducted by the Subcommittee for Radioisotope in vitro Test, the Medical Science and Pharmaceutical Committee, and the Japan Radioisotope Association, between 1978 to 2008. A total of 40 analytes for 26 hormones, 14 tumor markers and pharmaceutical drugs were investigated in participating facilities. In the first immunoassay control survey in 1978, samples were measured using only RI kits, however, non-RI kits increased gradually during the next 30 years. In the 30th immunoassay control survey, more than 90% samples were measured using non-RI kits. Coefficient variation (CV) of intra-kits has been decreasing yearly in all analytes for hormones as well as tumor markers. However, improvement of CV in inter-kits has not been seen in the past 30 years by a lack of international standards, although there has been continuous effort over the years for the standardization of immunoassay. Growth hormone (GH) deficiency has been diagnosed using various loading tests. However, the clinical diagnosis varies according to the GH kit used. Standardization for GH measurement has been possible by using recombinant GH as the standard among commercial GH kits. The diagnosis of subclinical Cushing's syndrome also varies according to the cortisol kits being used. Candidate reference measurement procedure and low level cortisol standards have been developed by the Biomedical Standard Section, of the National Metrology Institute of Japan. Standardization of measurement is necessary for improvement of immunoassay.

[A case of mycoplasma hominis infection on chronic refractory lower leg ulceration caused by livedo vasculopathy].

Mycoplasma hominis is a common inhabitant of the human urogenital tract and most frequently causes diseases of the genitourinary tract. Extragenital M. hominis infections are uncommon, with almost all occurring in immunosuppressed persons or those predisposed due to surgery or trauma. We report a case of non surgical, non-traumatic wound infection caused by M. hominis. A 28-year-old immunocompetent woman with livedo vasculopathy had an open wound on dorsum of her right foot with signs and symptoms of infection. However, gram staining of the wound swab demonstrated no microorganisms, and initial bacterial cultures did not reveal any microbial growth. After 2 days of culture, minute translucent colonies were appeared and subsequently identified as M. hominis. She was successfully treated with levofloxacin(LVFX). For the patient's being immune-competent, this infection seems to need a substantial bacterial transfer from the inhabitant organ. The transfer is likely mediated by the fluid's drop, for anatomical locations of vagina and the infection site on leg. Namely, the hinder leg infection is suspected to be caused by continual and heavy bacterial exposure originated from the vaginal M. hominis. This clinical case suggests that infections may occur even in normal immunological status if the site is close to, and lacks anatomical barrier from, the M. hominis inhabitant organ. Especially in infection at chronic refractory lower leg ulceraion, M. hominis should be considered as a causative organism.

Evaluation of a new rapid and fully automated electrochemiluminescence immunoassay for thyrotropin receptor autoantibodies.

BACKGROUND: Hyperthyroidism in Graves' disease is caused by autoantibodies to the TSH receptor (TSHR), and measurement of the TSHR autoantibody (TRAb) yields important information to diagnose and decide on the course of treatment of Graves' disease. We evaluated basic and clinical performance of a new, rapid, and fully automated electrochemiluminescence immunoassay Elecsys Anti-TSHR (Elecsys TRAb) for measuring serum TRAb. METHODS: For evaluation of basic performance of the assay, we carried out intra- and interassay precision studies using five serum pools and three serum pools, respectively, and the assay was compared with four commercial TRAb assays. Clinical performance of the assay was evaluated with sera from 298 patients with untreated Graves' disease, 220 patients with destructive (painless and subacute) thyroiditis, and 332 healthy volunteers. The optimal cutoff point, which was calculated by receiver operating characteristic (ROC) analysis with the above subjects, was then used to classify an independent sample set of 80 patients with untreated Graves' disease, and 152 patients with destructive thyroiditis. RESULTS: Intraassay coefficient of variation (CV) was 4.24% at 1.85 IU/L and interassay CV was 10.1% at 1.46 IU/L. All the correlation coefficient values calculated against four commercial assays were larger than 0.85. ROC analysis resulted in a specificity of 99.1% with a sensitivity of 97.0% at a decision limit of 1.86 IU/L from comparison with untreated Graves' disease and destructive thyroiditis. The cutoff point yielded a sensitivity of 87.5% and specificity of 96.7% with the independent sample set. CONCLUSION: In spite of the short measuring time of only 27 minutes, the assay showed the same or better results with the existing commercial products. The short measuring time would contribute to speedy, preconsultation diagnosis of thyroid disease, especially of Graves' disease.

[Anaerobiospirillum succiniciproducens septicemia].

We report the first case of septicemia caused by anaerobic spiral-shaped Gram negative bacilli, Anaerobiospirillum succiniciproducens in Japan. A 71-year-old male who had been suffered from terminal stage of liver cirrhosis and hepatocelluler carcinoma was admitted to our hospital for his symptoms of general malaise and increasing ascites on September 1, 2004. He developed diarrhea seven times a day on the eighth hospital day and had fever of 38.7 degrees C with WBC 12,600/microl and CRP 6.6 mg/dl on the next day. Blood culture grew Gram negative spiral bacilli. We initially could not identify the offending bacterium that resembled to Campyrobacter morphologically using commercially available indentification kits. However, 16SrRNA sequencing test revealed 100% compatibility with Anaerobiospirillum succiniciproducens.

[Evaluation of cardiac dysfunction after herceptin treatment in patients with metastatic breast cancer by echocardiography].

Herceptin (Trastuzumab) is a humanized recombinant monoclonal antibody that binds the extracellular domain of the human epidermal growth factor receptor 2 (HER2) and is used in the treatment of patients with HER2 overexpressing metastatic breast cancer. Treatment with Herceptin is generally well tolerated. At times, however, it exerts cardiac toxicity especially when used in combination with anthracyclines. We evaluated cardiac function before and after Herceptin treatment in nine patients with metastatic breast cancer by echocardiography, measuring ejection fraction (EF) and deceleration time (DcT). EF was significantly reduced after treatment(P<0.05). Although the present study failed to show significant changes in DcT, definite diastolic disturbance of the left ventricle did occur in a couple of patients. We conclude that cardiac dysfunction may be a common side effect of Herceptin even in early stages of treatment and that echocardiography will be a useful means of monitoring cardiac function in these patients.