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We experienced an outbreak of extensively drug-resistant pulmonary tuberculosis (XDR-TB) in a hemodialysis facility. The primary case involved a 51-year-old male hemodialysis patient, with a history of treatment for Mycobacterium tuberculosis infection seven years previously. There was no drug resistance, and the patient completely recovered after undergoing treatment with isoniazid (INH), rifampicin (RFP) and ethambutol (EB). He was admitted to another hospital due to a recurrence of pulmonary tuberculosis in June 2006. At first, he was treated with HRS [INH, RFP and streptomycin (SM)]; however, the drug regimen was changed to INH, EB, levofloxacin (LVFX) and kanamycin (KM) in August following the results of a drug susceptibility test. Although the patient was receiving outpatient tuberculous therapy, he was readmitted in June 2007 due to relapse and conversion of a sputum culture to positive status. Additionally, the XDR-TB organism was identified. Following these events, five staff members of the hemodialysis facility and a member of the patient's family were diagnosed with XDR-TB infection. The staffs who were infected with XDR-TB had worked in the same dialysis room, drug resistance was found in all cases and drug resistant gene mutations were found in three cases; therefore, we considered this to be an outbreak. As XDR-TB infection was suspected in all cases, no patients took drugs to treat latent tuberculosis infection (LTBI). Regarding the causes of the outbreak, the first is the delay of four months in making a diagnosis of re-exacerbation of tuberculosis. Second, in Case 2, the patient developed laryngeal and tracheobronchial tuberculosis after first being diagnosed with asthma, and the tuberculosis diagnosis was delayed. Third, the sputum smear of Case 2 was strongly positive. There is only one previously reported outbreak of XDR-TB in Japan; therefore, we consider this outbreak to be educational.

Objective: To conduct a clinical investigation of patients with multidrug-resistant (MDR) tuberculosis who received either drug therapy alone or drug therapy in combination with surgery., Subjects and Methods: A total of 56 patients with MDR tuberculosis who were admitted to hospitals of the National Hospital Organization in the Kyushu region between January 2004 and September 2009 and received drug therapy either alone or in combination with surgery were investigated., Results: As surgery could not be performed in patients with advanced age or with bilateral extensive lesions, only 12 patients (21%) were able to undergo surgery. Initial drug resistance was seen in 10 patients (23%) in the drug therapy group and four patients (33%) in the combination therapy group. Underlying diseases included diabetes in 15 patients (34%) in the drug therapy group and in 6 patients (50%) in the combination therapy group. Negative conversion of the sputum culture result was observed in 43% in the drug therapy group and in 75% in the combination therapy group. The death within three years was seen in 20 patients (45%) in the drug therapy group and 1 patient (8%) in the combination therapy group. In the drug therapy group there were more cases with resistance to 5 drugs, resistance to levofloxacin (LVFX), and/or kanamycin (KM) in those who died of tuberculosis than in non-tuberculous death cases., Conclusion: Resistance to 5 drugs, resistance to LVFX, and resistance to KM were contributing factors of tuberculous death. Patient's operability was one of the factors associated with a good prognosis.

Short course regimens; 2HRZ (E)(S)/4HR (E), 6HRS (E)/3-6HR and 6-9HR have been accepted as a standard chemotherapy (SC) for initial treatment of pulmonary tuberculosis in Japan. We studied the frequency of the treatment completion, the causes of the treatment failure and the outcome of the patients in whom INH or RFP was discontinued within 6 months after starting SC. The subjects included 597 newly diagnosed culture positive pulmonary tuberculosis patients admitted to 16 national hospital in 1996. Results were as follows. 1. In 47 (7.9%) of the 597 patients, either INH (19; 3.2%) or RFP (33; 5.5%) was discontinued. These 47 cases were defined as a SC incompleted group and the other 550 as a SC completed group. 2. The patients in the SC incompleted group were seen more frequently in the ages of 20s (11.9%), 50s (10.9%), 60s (11.7%) or 70s (11.4%). 21 (13.6%) of 154 female patients and 26 (5.9%) of 443 male patients were in the SC incompleted group. 3. The causes of cessation of INH or RFP were drug side effects (33; 5.5%), drug resistance (10; 1.7%) and complications or underlying diseases (8; 1.3%). 4. Fever or eruption (19; 3.2%) and drug induced hepatitis (12; 2.0%) were frequently seen as drug related side effects causing the cessation of INH or RFP. 5. The rate of culture negative conversion of TB bacilli at 6 months after the start of the treatment was 98.9% in the SC completed and 88.9% in the SC incompleted group respectively. In the SC incompleted group, there were three cases continuously positive and two other patients who relapsed and became culture positive again. In these five patients, INH or RFP was discontinued because of drug resistance.

Clinical efficacy and safety of pareteral sulbactam/ampicillin (SBT/ABPC) was compared with cefotiam (CTM) in a randomized clinical trial of pneumonia in the elderly at 13 National Hospitals of Kyushu island. 37 patients received SBT/ABPC 3 g i.v., b.i.d., and 31 patients received CTM 1 g i.v., b.i.d. for 7 to 14 days. 1. 68 patients (37 for SBT/ABPC and 31 for CTM) were evaluated for safety. No statistical differences were noted in the patients' backgrounds of either group. 2. The clinical efficacy of SBT/ABPC was 96.3% (26/27 cases) while CTM was 75.2% (17/23 cases). This was found to be statistically significant (Fisher's exact test: p < 0.05). 3. 100% of evaluated cases (10 for SBT/ABPC and 4 for CTM) showed bacterial elimination. 4. No side effects were observed in the study. 5. Abnormal laboratory findings were noted in 10.8% (4/37 cases) for SBT/ABPC and 3.2% (1/31 cases) for CTM. The major adverse events were mild elevation of GOT, GPT and A1-P for SBT/ABPC, and mild platelets overproduction for CTM. No statistical differences were noted in both groups. These results are consistent with SBT/ABPC as a highly effective antibiotic in the treatment of elderly patients with pneumonia.

Forty-eight cases of tuberculous pleurisy were examined and the following results were obtained. (1) Most of the patients were male, and there was no significant age and underlying diseases. (2) Fever and chest pain were observed mainly in younger patients, and sputum and dyspnea in older patients. (3) All of the cases examined had exudative pleural effusion, and increased ADA activity was frequently observed. (4) Mycobacterium tuberculosis was detected in the sputum of 65%, and also in the pleural effusion of 28% of the patients. The pathological diagnosis of tuberculosis was made by pleural biopsy in 83% of the patients, suggesting that pleural biopsy is very useful in the diagnosis of tuberculosis pleurisy. (5) The prognosis of the patients with tuberculosis pleurisy was good. Steroid therapy was generally ineffective.

High-performance liquid chromatography (HPLC) with electrochemical detection has been developed for the trace analysis of electrochemically active substances in biological fluids such as catecholamines. The recent development of this system, both instruments and application, has been reviewed. The principle of instrument and newly developed electrode for electrochemical detector have been described at the first section. Series electrodes, especially with coulometric detection, gave much higher selectivity to the analysis of biological substances. The application of HPLC with electrochemical detection to the determination of estrogens in biological fluids clarified the metabolic pathway of catechol estrogens. The applicability to the determination of vitamin D3 and related compounds has been also suggested. For the purpose of extending the applicability of HPLC with electrochemical detection to electro-inactive compounds, pre- and post-column labeling methods have been developed. Pre-column derivatization reagents possessing ferrocene as an electrophore provided a selective and sensitive response to the detector, because of their high-reversibility and low applied potential in the redox reaction. Post-column reaction by using immobilized enzyme reactor has been widely used for the determination of acetylcholine and choline in biological fluids.

Idiopathic herniation of the spinal cord is a very rare disease, only 2 cases being so far reported in the literature. A 61-year-old man with a gradual loss of power in his lower extremities was diagnosed as intradural arachnoid cyst, and underwent operation. During operation, not only an arachnoid cyst was observed dorsally, but was also duplicated the dura mater ventrally. In the latter lesion, a ventral part of the spinal cord was herniated from a defected area of the dural inner layer. Although this dural inner layer as well as the arachnoid cyst was resected, his clinical symptoms remained unchanged after operation. When a shift of the spinal cord is detected in an image, we should precisely determine the relationship between the spinal cord and the dura mater during operation with consideration of a possibility of the presence of idiopathic herniation of the spinal cord.

The IgE mediated reactions such as 48 hr homologous passive cutaneous anaphylaxis (PCA) and active anaphylactic bronchoconstriction in rats were inhibited in a dose dependent manner by treatment with 7-acetyl-5-oxo-5H-[1]benzopyranol[2,3-b] pyridine (Y-9000) and disodium cromoglycate (DSCG) given intraperitoneally. The inhibitory activity of Y-9000 was to the same extent as that seen with DSCG. The IgE mediated reactions were also inhibited by oral treatment with Y-9000 but not with DSCG. In addition, the treatment with Y-9000 resulted in inhibition of IgG mediated reaction such as anaphylactic asthma in the passively sensitized guinea pigs and 4 hr heterologous PCA in rats. However, DSCG failed to prevent these reactions. Y-9000 also inhibited the active systemic anaphylaxis of the mouse and non-immunological reactions in rats such as histamine release after an intraperitoneal injection of dextran, anaphylactoid reaction and paw edema induced by the dextran, egg white or carrageenin. This agent had a stimulating effect on the adrenals, and showed glucocorticoid like activity, but bronchodilator and antagonistic activities on chemical mediators were nil. These results suggest that the anti-allergic activities of Y-9000 are elicited by inhibiting the release of allergic mediators in a manner similar to DSCG, and are partially mediated by stressor activity.

The optical resolution of racemic 4-[alpha-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid (dl-I), a new potent and long lasting thromboxane synthetase inhibitor, was investigated. (S)-3-(3,5-Dinitrobenzoylthio)-2-methylpropionyl group was introduced to alpha-hydroxy moiety of methyl ester of dl-I by three steps of reaction to give the corresponding ester compound (VIa). Then, two diastereomers of VIa, alpha-VIa and beta-VIa, were separated by column chromatography using on silica gel. Alkaline hydrolysis of alpha-VIa and beta-VIa, followed by reactions with sodium ethylate gave optically pure sodium salts of (-)-I and (+)-I, respectively. The separative determination methods for the diastereomers of VIa, and for the enantiomers of the sodium salts of dl-I by high performance liquid chromatography were also established.

The pro-drugs of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid(I) with a potent anti-inflammatory activity were synthesized in order to reduce its gastrointestinal side effects. Various esters synthesized were evaluated for their anti-inflammatory activity and ulcerogenicity. Among the compounds maintaining a potent activity of I, N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate (II-18) showed excellent biopharmaceutical characteristics. The ulcerogenic effect of II-18 on the rat gastric mucosa was about 3 times less than that of I. It was suggested that II-18 may be an useful biolabile pro-drug for I among the compounds tested.

A 75 year old woman who was admitted to Higashisaga National Hospital due to chronic bronchitis showed a high fever (39.2 degrees C) and marked lymphadenopathy of the bilateral inguinal lymph-nodes. Chest X-ray showed diffuse infiltration. Cryptococcus was detected in biopsied lymph-nodes. Although 5-fluorocytosine, miconazole, amphotericin-B were administered for six weeks, she died and an autopsy was performed. Disseminated cryptococcosis was observed in the lung, liver, spleen, kidney, bone marrow, and lymph-nodes of the lung hilum, paratrachea, retroperitoneum, gall bladder and groin. She was a human T cell leukemia type I (HTLV-I) carrier, and this could be related to disseminated cryptococcosis.

Several imidazolylpyridinemethanols and imidazolylbenzenemethanols were prepared and evaluated for an inhibitory activity against arachidonic acid-induced platelet aggregation. The result shows that the arylmethanol moiety is essential for the activity and may correspond to the 15-OH group of prostagrandin H2 (PGH2). Among the compounds tested, 4-[alpha-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid (XV) was found to have a potent inhibitory activity and a long duration of action. Structure-activity relationships are also discussed briefly.