Prevalence of hepatitis B virus infection in patients with rheumatic diseases in Tohoku area: a retrospective multicenter survey.

Hepatitis B virus (HBV) reactivation has been increasingly recognized in patients receiving chemotherapy and immunosuppressive therapy; however, the prevalence of HBV infection and rate of HBV screening in patients with rheumatic diseases remains unclear. In this study, we aimed to assess the prevalence of HBV infection and fulminant HBV hepatitis in patients with rheumatic diseases. We also investigated the rate of HBV screening before immunosuppressive therapy in patients with rheumatic diseases. A retrospective questionnaire survey was conducted in the North-east area (Tohoku) of Japan. Questionnaires, comprising 6 questions, were sent to 318 rheumatologists in May 2010, and responses were gathered until June 2011. In total, 71 rheumatologists (22.3%) responded to the survey. We enrolled 7,650 patients with rheumatoid arthritis (RA) and 1,031 patients with systemic lupus erythematosus (SLE). When limited to institutes at which almost all (≥ 90%) patients were tested for HBV serology, 1.1% (40/3,580) patients with RA and 0.3% (3/1,128) patients with SLE were positive for hepatitis B surface antigen (HBsAg), and 25.2% (177/703) patients with RA and 13.7% (34/248) patients with SLE were positive for hepatitis B core antibody (HBcAb). About one-third of rheumatologists did not check HBsAg and more than half did not check hepatitis B surface antibody (HBsAb) or HBcAb at all before therapy. Fulminant HBV hepatitis was observed in 1 RA patient who was current HBV carrier. In conclusion, the prevalence of HBV infection is high in patients with RA and SLE. HBV screening before immunosuppressive therapy should be strictly performed.

The performance of the BD geneOhm MRSA™ assay for MRSA isolated from clinical patients in Japan, including the effects of specimen contamination and ways to improve it.

The BD geneOhm MRSA™ assay has been increasingly used in recent years, and it is possible to use it to screen and detect methicillin-resistant Staphylococcus aureus (MRSA) from a specimen within 2 h. The purpose of the present study was to evaluate the performance, i.e., the specificity and sensitivity, of the BD geneOhm MRSA™ assay to detect MRSA. Its specificity was assessed to be 100% compared to bacterial culture methods, which are commonly used in medical laboratories. Its bacterial limit of detection was over 10 colony-forming units (cfu) per reaction, although MRSA was detected at a cfu below 10 per reaction in a few samples. Additionally, the effect of MRSA isolate contamination was examined. While contamination with protein or other bacteria did not affect the outcome, contamination with a high concentration of blood resulted in an unresolved outcome. To inactivate polymerase chain reaction (PCR) inhibitors, the DNA samples were freeze-thawed prior to the BD geneOhm MRSA™ assay, which led to the sensitivity of the assay increasing. In summary, the BD geneOhm MRSA™ assay is rapid and shows high specificity and sensitivity of cultured MRSA isolates. It will, therefore, be a valuable diagnostic tool for detecting MRSA in specimens from clinical patients.

Changes of low back pain after vascular reconstruction for abdominal aortic aneurysm and high aortic occlusion: a retrospective study.

BACKGROUND: The purpose of the present study is to clarify the influence of acute and chronic interruption of blood flow from lumbar arteries as well as the influence of vascular reconstruction on low back pain, back muscles, and lumbar discs. METHODS: Subjects were 34 patients with AAA in whom vascular reconstruction was performed. A second group was comprised of 9 patients with HAO. The presence of low back pain before surgery and at follow-up examination was retrospectively examined in the AAA group and the HAO group to investigate postoperative changes. The CSA and degeneration of the multifidus muscle and the lumbar discs on magnetic resonance imaging were assessed in the AAA group and control group. RESULTS: Low back pain, significant atrophy, or degeneration of the multifidus muscle or degeneration of the lumbar disc did not newly develop after surgery in the AAA group. These results indicated that acute interruption of lumbar arteries did not induce the development or deterioration of low back pain and organic changes in the back muscles or lumbar discs. The frequency of low back pain before surgery was significantly higher in the HAO group than that in the AAA group. However, the frequency of low back pain after surgery did not differ significantly between the 2 groups because low back pain in the HAO group was improved after surgery. CONCLUSION: The finding that low back pain was improved by merely performing treatment for the vascular system might provide support for the presence of vascular backache.

Synthesis and structure-activity relationships of novel 7-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids as antitumor agents. Part 2.

We have previously reported that a series of 7-substituted 6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids possess moderate cytotoxic activity. In a further attempt to find clinically useful antitumor agents, we investigated the structure-activity relationships (SARs) of a new series of compounds obtained by changing the C-6 position of the fluorine atom in addition to the C-5 and C-7 positions and evaluating their cytotoxic activity against several murine and human tumor cell lines. Our results showed that the 6-unsubstituted 1,8-naphthyridine structure had the most potent cytotoxic activity against murine P388 leukemia twice that of the 6-fluoro analogue. In addition, introduction of an amino group at the C-5 position did not have any substantial effect on the cytotoxic activity, while both the 5-chloro and 5-trifluoromethyl groups decreased the cytotoxic activity by 5- to 10-fold. Moreover, aminopyrrolidine derivatives at the C-7 position showed more potent cytotoxic activity than other amines or carbon derivatives. Among the 7-(3-aminopyrrolidinyl) derivatives, the trans-3-methoxy-4-methylaminopyrrolidinyl derivative (27l) was determined to have potent cytotoxic activity in both in vitro and in vivo assays and high water solubility. Finally, the (S,S)-isomer (AG-7352, 3) of 27l, with a cytotoxic activity against human tumor cell lines more potent than that of etoposide, was selected for further development.

Synthesis and structure-activity relationships of novel 7-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids as antitumor agents. Part 1.

In an attempt to search for clinically useful antitumor agents, we have discovered that a series of 1,7-disubstituted-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids possessed moderate cytotoxic activity. We investigated the structure-activity relationships in this series of compounds by changing N-1 and C-7 positions and the core ring structure itself and evaluated the synthesized compounds against several murine and human tumor cell lines. These modifications led us to the following findings. (1) The 2-thiazolyl group at the N-1 position of the naphthyridine structure is the best substituent for antitumor activity. (2) Regarding core ring structure, the naphthyridine derivative is the most active followed by pyridopyrimidine analogue. (3) At the C-7 position, aminopyrrolidine derivatives are more effective than other amines or thioether derivatives. Finally, the trans-3-amino-4-methoxypyrrolidinyl derivative (43j) and the 3-amino-3-methylpyrrolidinyl derivative (43f) as well as 3-aminopyrrolidinyl derivative (AT-3639, 1) were determined to be effective in in vitro and in vivo antitumor assays, and their activity was comparable to that of etoposide.

Start and initial results of the Fukushima Prefecture acute myocardial infarction registration survey.

Acute myocardial infarction (AMI) remains one of the most serious heart diseases and elucidation of its pathogenesis and advances in treatment strategies have been desired. In 2009, to understand the status of AMI in Fukushima Prefecture for improving treatment outcomes, a new AMI registration survey system was conducted throughout the prefecture. A total of 1,556 cases were registered in the initial 2 years from 2009 to 2010. The hospital-based overall incidence of AMI in Fukushima Prefecture was 37.9 people per population of 100,000 per year. Mortality from AMI within 30 days of onset was 10.2%. We report herein the actual situation of AMI onset and treatment in Fukushima Prefecture based on the initial results of the survey.

Epidemiological and microbiological analysis of community-associated methicillin-resistant Staphylococcus aureus strains isolated from a Japanese hospital.

Reports of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have recently increased in Japan; however, these studies contain limited information on their epidemiology. We performed a single-center study in the Tokyo Medical University Hospital located in Shinjuku, a central area of Tokyo, Japan. From 2,099 MRSA isolates obtained during July 2007 to March 2009, we selected 44 MRSA isolates with a MIC of <2 µg/mL for imipenem. Among 44 isolates, 28 strains had type IV or type V SCCmec, and we classified them as CA-MRSA. We identified only 1 Panton-Valentine leukocidin (PVL)-positive MRSA strain, which belonged to SCCmec type V. The PVL-positive CA-MRSA strain was isolated from a patient with multiple subcutaneous abscesses. The patient had returned to Japan from India; thus, the strain may have been contracted from outside of Japan. Thirteen (46.4%) and 15 strains (53.6%) were isolated from outpatients and inpatients, respectively. The major sites of infection included the respiratory tract (8 strains, 28.6%), skin/soft tissue (4 strains, 14.3%), and nasal cavity (4 strains, 14.3%). It is important to note that the most common site of CA-MRSA infection in inpatients was the respiratory tract; respiratory infections with CA-MRSA frequently cause severe infectious diseases.

Synthesis and structure-activity relationships of 3-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridines as novel antitumor agents.

In order to obtain clinically useful antitumor agent, we have designed and synthesized various 3-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridines, and evaluated their cytotoxic activity. The series of novel 3-substituted derivatives synthesized in this study showed good antitumor activity against murine P388 leukemia. Particularly, the 3-formyl 1,8-naphthyridine displayed an antitumor activity equal to that of the 3-carboxy 1,8-naphthyridine against murine and human tumor cell lines as well as in vivo test for mouse leukemia. These results demonstrate that the carboxy group at the C-3 position of 1,8-naphthyridine ring is not essential for antitumor activity. In addition, the trend of cytotoxic activity for the 3-substituted 1,8-naphthyridines was different from that of antibacterial activity.

Rapid diagnosis of bacterial meningitis by using multiplex PCR and real time PCR.

BACKGROUND: The purpose of the present study was to improve a method for a rapid identification of bacteria in bacterial meningitis by using multiplex polymerase chain reaction (PCR). METHODS: Ten species of bacteria which cause meningitis in children were investigated, and cerebrospinal fluid from patients with purulent meningitis was studied. The ribosomal RNA genes of bacteria are essential, and are highly conserved in the bacterial kingdoms with consensus region. The 23S rRNA region shows a larger variation among species than in the 16S rRNA region. The authors set primers in the universal region and specific region of 23S rRNA, then amplified these regions by multiplex PCR and real-time PCR. RESULTS: All species of bacteria showed one band by PCR using universal primer. Haemophilus influenzae and Streptococcus pneumoniae showed two bands by multiplex PCR using a combination of universal primers and specific primers. The authors detected H. influenzae within 15 min by using real-time PCR. CONCLUSION: It was possible to identify clinically significant bacterial species in cerebrospinal fluid by multiplex PCR, and to identify H. influenzae by real-time PCR within a short period.