Clinico-radiological features of subarachnoid hyperintensity on diffusion-weighted images in patients with meningitis.

AIM: To investigate the clinical and radiological features of meningitis with subarachnoid diffusion-weighted imaging (DWI) hyperintensity. MATERIALS AND METHODS: The clinical features, laboratory data, and radiological findings, including the number and distribution of subarachnoid DWI hyperintense lesions and other radiological abnormalities, of 18 patients seen at five institutions were evaluated. RESULTS: The patients consisted of eight males and 10 females, whose ages ranged from 4 months to 82 years (median 65 years). Causative organisms were bacteria in 15 patients, including Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus agalactiae, Staphylococcus aureus, Klebsiella pneumoniae, and Listeria monocytogenes. The remaining three were fungal meningitis caused by Cryptococcus neoformans. Subarachnoid DWI hyperintense lesions were multiple in 16 of the 18 cases (89%) and predominantly distributed around the frontal lobe in 16 of the 18 cases (89%). In addition to subarachnoid abnormality, subdural empyema, cerebral infarction, and intraventricular empyema were found in 50, 39, and 39%, respectively. Compared with paediatric patients, adult patients with bacterial meningitis tended to have poor prognoses (7/10 versus 1/5; p = 0.1). CONCLUSION: Both bacterial and fungal meningitis could cause subarachnoid hyperintensity on DWI, predominantly around the frontal lobe. This finding is often associated with poor prognosis in adult bacterial meningitis.

Radiation safety design for the J-PARC Project.

The High-Intensity Proton Accelerator Project, named J-PARC, is in progress, with the aim of enabling studies on the latest basic science and the advancement of nuclear technology. In the project, a high-energy proton accelerator complex with the world's highest instantaneous intensity is under construction. In order to establish a reasonable shielding design, both simplified and detailed design methods were used in the shielding design of J-PARC. This paper reviews the present status of the radiation safety design study for J-PARC.

KL-6 as an indicator for lymphocytic interstitial pneumonia (LIP) in a human T-lymphotrophic virus type 1 (HTLV-1) carrier.

A 59-year-old woman was admitted to our hospital complaining of a productive cough, dyspnea on effort, and low-grade fever. Although chest X-rays showed no marked abnormalities, her level of serum KL-6 was extremely high. We therefore suspected the presence of interstitial pneumonia. High-resolution computed tomography (CT) scan revealed infiltrative shadows in S6 of the right lung, and her serum was positive for antihuman T-lymphotropic virus type 1 (HTLV-1) antibodies. From the clinical symptoms, radiographic findings, and histological findings, the diagnosis was probable lymphocytic interstitial pneumonia (LIP). After high-dose corticosteroid therapy, the level of serum KL-6 decreased rapidly. We conclude that KL-6 is a convenient and reliable marker for evaluating the activity of pulmonary manifestations in HTLV-1 carriers and that it is especially useful in monitoring the effectiveness of treatments.

Syndrome of inappropriate secretion of ADH (SIADH) following cisplatin administration in a pulmonary adenocarcinoma patient with a malignant pleural effusion.

We report a patient with pulmonary adenocarcinoma complicated by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) following systemic chemotherapy with cisplatin (CDDP) and vindesine (VDS). A 66-year-old woman was diagnosed as having pulmonary adenocarcinoma with malignant pleural effusion following investigations for cough and dyspnea. After drainage of the effusion she received combination chemotherapy with CDDP and VDS. She developed SIADH 48 hours following chemotherapy. Interestingly, the use of carboplatin (CBDCA) and VDS in the subsequent treatment course was well tolerated indicating that the SIADH was most likely to have been induced by administration of CDDP.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1999)].

From October 1999 to September 2000, we collected the specimen from 430 patients with lower respiratory tract infections in 17 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 515 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 506 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 101, Haemophilus influenzae 104, Pseudomonas aeruginosa (non-mucoid) 58, P. aeruginosa (mucoid) 11, Moraxella subgenus Branhamella catarrhalis 41, Klebsiella pneumoniae 18, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or above of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 57.7%. Vancomycin and arbekacin showed the most potent activities against MRSA without detection of ABK-resistant strain (MIC: 64 micrograms/ml) and decrease of VCM-sensitive strains those were found in 1998. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) decreased to 34.7% from 46.0% in 1998. The frequency of PRSP was 3.0%, being the least number after 1991. Carbapenems showed strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 101 strains with MIC of 0.063 microgram/ml. Generally, all drugs showed strong activities against H. influenzae with MIC80s of 4 micrograms/ml or below. MICs of ofloxacin ranged between 0.063 microgram/ml and 4 micrograms/ml in 1998, however, those were 0.125 microgram/ml or below in all H. influenzae in 1999 showing the strongest activity. Tobramycin and ciprofloxacin showed strong activities against P. aeruginosa (both mucoid and non-mucoid) with MIC80s of 1 microgram/ml. Number of isolated P. aeruginosa (mucoid) was little as 11, however, the susceptibilities to all drugs were better than P. aeruginosa (non-mucoid). K. pneumoniae showed good susceptibilities to all drugs except for ampicillin with decreasing of low-sensitive strains compared to those detected in 1998. Also, all drugs generally showed strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or below. The drug which showed the strongest activity was imipenem inhibiting all 41 strains with MIC of 0.063 microgram/ml. On the patients' characteristics, the number of patients aged 80 years or older who had been increased was decreased in 1999 in the distribution by age. The percentage of the elderly patients aged 70 years or older was 47.0%, which occupied almost a half number of the total patients as in the last year. As for the incidence by disease, bacterial pneumonia and chronic bronchitis were the highest. They were noted in 37.9% and 30.5% of the patients, respectively. In 1999, bronchial asthma was frequently observed as compared in recent years. It was noted in about 10% of the patients which is the same % as in bronchiectasis. We examined the number of strains from these patients with infections before and after administration of antibiotics. In patients with bacterial pneumonia, the number of isolated strains was almost the same between those before and after administration. However, in patients with chronic bronchitis, the number of strains remarkably decreased to less than the half of the total after administration of antibiotics in the last year, but it decreased to 2/3 of the total in 1999. On the administration of antibiotics and isolated bacteria by the day of administration, the bacteria which were isolated more before administration were H. influenzae in 28.4%, S. pneumoniae in 25.7%, M. (B.) catarrhalis in 12.0% and S. aureus in 10.6%. The frequency of S. aureus after administration over 15 days was almost the same as that before administration, but the frequency of P. aeruginosa (both mucoid and non-mucoid) was 36.8% which was higher than that before administration. The frequency of isolated S. pneumoniae was decreased after administration and none of them was isolated after completion of administration. However, that of H. influenzae was decreased to 7.1% after administration within 3 days, and many H. influenzae were isolated after completion of administration as 21.4%.

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1999). I. Susceptibility distribution].

The bacterial strains isolated from patients diagnosed as having urinary tract infections (UTIs) in 9 institutions in Japan were supplied between the period of August 1999 to July 2000. Then, the susceptibilities of them to many kinds of antimicrobial agents were investigated. The number of them were 499 strains. The breakdown of these strains was Gram-positive bacteria as 31.3% and Gram-negative bacteria as 68.7%. Susceptibilities of these bacteria to antimicrobial agents were as follows; vancomycin (VCM), ampicillin (ABPC) and imipenem (IPM) showed strong activities against Enterococcus faecalis. The increase of low-susceptible strains which was noticed in the former year showed a slight recovery in this year. VCM showed a strong activity against MRSA preventing growth of all strains with 1 microgram/ml. In addition, the activity of arbekacin (ABK) was also strong with the MIC90 of 2 micrograms/ml against MRSA. However, MSSA and MRSA showing low susceptibilities were detected in one strain each (MIC: 16 micrograms/ml and 32 micrograms/ml, respectively). Carbapenems showed high activities against Citrobacter freundii and Escherichia coli. Meropenem (MEPM) prevented growth of all strains within 0.125 microgram/ml. Quinolone resistant E. coli decreased in this year compared with those in the last year, that percentage was less than 5%. Almost all drugs showed strong activities against Klebsiella pneumoniae and Proteus mirabilis. MEPM and carumonam (CRMN) prevented growth of all strains within 0.125 microgram/ml. On the other hand, one strain of K. pneumoniae showing resistance to cefaclor (CCL) and one strain of P. mirabilis showing low susceptibility to most of cephems were detected. Against Pseudomonas aeruginosa, almost drugs were not so active. The MIC90s of carbapenems were 8 micrograms/ml and those of all other drugs were more than 16 micrograms/ml.

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1999). II. Background of patients].

Five-hundred forty four bacterial strains isolated from 412 patients diagnosed as having urinary tract infections (UTIs) in 9 institutions in Japan were supplied between the period of August 1999 to July 2000. Then, the clinical background of patients were investigated such as sex, age and type of infections, infections and kind of bacteria, frequency of isolation of bacteria by age and infections, bacteria and infections by timing of administration of antibiotics, and bacteria and infections by surgical procedures. About the relationship between age and sex of patients and type of infections, the number of male patients aged less than 50 years was few, and complicated UTIs without indwelling catheter was the most frequent. In females, the number of patients aged less than 20 years was few. Complicated UTIs without indwelling catheter was the most frequent among female patients aged between 40 to 59 years, in other age groups, uncomplicated UTIs was most frequent. As for type of infections and kind of bacteria, Escherichia coli decreased when the infections became complicated, and Pseudomonas aeruginosa and Enterococcus faecalis increased when the infection became complicated. Considering this result by age of patients, isolation frequency of E. coli was gradually decreased with aging in patients aged more than 20 years with uncomplicated UTIs or complicated UTIs without indwelling catheter. The isolation frequencies of E. faecalis and Staphylococcus aureus were gradually increased with aging in complicated UTIs without indwelling catheter. In patients with complicated UTIs with indwelling catheter, there was no difference between age group, and P. aeruginosa and E. faecalis were frequently isolated. As for type of causative organisms in UTIs before and after the administration of antibiotics, the isolation of bacteria was remarkably decreased after administration in patients with uncomplicated UTIs and complicated UTIs without indwelling catheter. E. coli decreased after administration of antibiotics, and P. aeruginosa and E. faecalis increased after administration in patients with all infections. As for type of causative organisms in UTIs and surgical procedures, E. coli were more frequently isolated in patients with uncomplicated UTIs when surgical procedures were experienced. Also, Klebsiella spp. and E. faecalis were more frequently isolated in patients with surgical procedures. However, in complicated UTIs, type of causative organisms had no relationship with surgical procedures.

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1999). III. Secular changes in susceptibility].

The bacteria (Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as having urinary tract infections (UTIs) in 9 institutions in Japan were supplied between the period of August 1999 to July 2000. Then, the susceptibilities of these bacteria to various antimicrobial agents were examined and the results were compared with those obtained between 1991 and 1998. Comparison was made by classifying strains isolated from patients into those with uncomplicated UTIs and those with complicated UTIs (including with or without indwelling catheter). About E. faecalis, increase of low sensitive strains noted in the former year showed a decreasing tendency, however, one strain each with MIC of 4 micrograms/ml to vancomycin (VCM) was detected in patients with both uncomplicated and complicated UTIs. As for S. aureus, many sensitive strains to cephems, imipenem (IPM) and VCM were noted, and each MIC50 was better than that in the former years. S. aureus strains showing low susceptibility to arbekacin (ABK) were detected in patients with complicated UTIs in this year as well as in the former year, and one strain each with MIC of 16 micrograms/ml and 32 micrograms/ml was detected. Susceptibilities of E. coli were effective to all drugs except for penicillins and minocycline (MINO). Decrease of low sensitive strains was also noted in all drugs except for quinolones. Each MIC90 of ciprofloxacin (CPFX) and sparfloxacin (SPFX) in patients with complicated UTIs against E. coli was 3 degrees classes lower than that in patients with uncomplicated UTIs. As for Klebsiella pneumoniae, decrease of low sensitive strains to cephems was noted in patients with uncomplicated UTIs in 1998. In 1999, low sensitive strains decreased also in patients with complicated UTIs, and few were detected. Susceptibilities of K. pneumoniae to quinolones were effective as compared with those in the former years with the MIC80s of 0.125 microgram/ml or below without detection of low sensitive strains. One low sensitive strain of K. pneumoniae with MIC of 8 micrograms/ml was detected for gentamicin (GM). Susceptibilities of P. aeruginosa to carbapenems were notable. The MIC90 of meropenem (MEPM) and IPM was 4 micrograms/ml each which was 2 degrees better than that in 1998. Resistant P. aeruginosa strains to other drugs except for monobactams decreased in 1999.

Induction of cytochrome P450 3A4 by docetaxel in peripheral mononuclear cells and its expression in lung cancer.

Several recent studies have demonstrated that the cytochrome p450 (CYP) family plays an important role in the metabolism of taxanes. However, the role of CYP gene expression in tumors and peripheral mononuclear cells (PMN) is unknown. We therefore investigated the levels of CYP3A4 and CYP2C gene expression using reverse transcription polymerase chain reaction (RT-PCR) in PMN from 16 previously untreated lung cancer patients to determine whether the expression of the two genes is induced by docetaxel (TXT). Neither the CYP3A4 nor the CYP2C gene was induced after administration of carboplatin (CBDCA) alone. Expression of the CYP3A4 gene was induced by the administration of TXT alone or TXT and CBDCA, but expression of the CYP2C gene was unaffected. We also measured the expression of both genes using RT-PCR in 20 autopsy samples (ten non-small-cell lung cancers and their corresponding normal lung tissues) obtained from patients who had not received any chemotherapy during life. The level of CYP2C gene expression in samples of lung cancer was significantly higher than in normal lung tissue, but the level of CYP3A4 gene expression was not. These results suggest that the CYP3A4 gene is induced by TXT, and that it plays an important role in intracellular TXT metabolism.

[Epidemiological study on vancomycin-resistant enterococci from fecal samples in the east area of Japan].

Recently, Vancomycin-resistant enterococci (VRE) have become important nosocomial pathogens in the world. In Japan, the VRE-infection was first reported in 1996. However, an epidemiological study on VRE has not been aggressively done in Japan. We conducted a survey study to explore the incidence and antimicrobial susceptibility of vancomycin-resistant enterococci isolated from fecal samples at 45 hospitals in the east area of Japan (Kanto, Koshinetsu, Tohoku, and Hokkaido) during June 1998 to March 1999. The Enterococcosel agar containing vanocomycin (BBL) was used for screening VRE from fecal samples in each hospital. The susceptibilities of the isolates to 8 antimicrobials were determined by the broth microdilution method and the definitions of resistance were based on current standards of the NCCLS standards. The VRE genotypes (vanA, vanB, vanC1, and van C2/3) were confirmed by amplifying the respective genes by PCR. Eight hundred and ninety four strains of enterococci were tested by the microtiter plates hybridization method (WAKUNAGA SEIYAKU, Japan). One thousand five hundred eighty three strains of enterococci were collected from 6,914 patients in 45 hospitals. These strains included 72 (4.5%) strains Enterococcus faecalis, 33 (2.1%) strains Enterococcus faecium, 17 (1.1%) strains Enterococcus avium, 1,040 (65.7%) strains Enterococcus gallinarum, 386 (24.4%) strains Enterococcus cassliflavus, and 35 (2.2%) strains Enterococcus flavescens. These strains of vancomycin-resistant E. faecalis were isolated from 3 patients, two of these 3 strains had van A gene and other one had van B gene. Those 3 strains were in the Kanto area, and 2 of 3 strains were in Tokyo, Generally, though van A type VRE was highly resistaant to both vancomycin and teicoplanin. In our study, two strains of van A type E. faecalis were highly resistant to vancomycin (MICs > 128 micrograms/ml) and susceptible to teicoplanin with MICs 4 micrograms/ml. Those two strains were different in susceptibilities of minocycline and ofloxacin. The result of the analysis of PFGE had also different patterns. VanB type E. fecalis was highly resistant to vancomycin and susceptible to teicoplanin (MICs 0.25 microgram/ml). For ampicillin and imipenem, 3 strains of E. faecalis were susceptible (MIC < or = 1 microgram/ml). One of 562 strains of E. gallinarum had vanB and vanC1 genes and was moderately resistant to vancomycin and susceptible to teicoplanin. All strains of E. casseliflavus and E. flavescens had vanC2/C3 gene only. All strains of E. faecium and E. avium did not detect van genes. From this result, it was supposed that VRE were very rare in the east of Japan.

SGLT gene expression in primary lung cancers and their metastatic lesions.

Cancer cells show increased glucose uptake and utilization in comparison with their normal counterparts. Glucose transporters play an important role in glucose uptake. We previously reported the differential gene expression of the GLUT family in primary and metastatic lesions of lung cancer. To investigate the role of Na( +) / glucose cotransporter (SGLT) genes in cancers, we examined the levels of expression of SGLT1 and SGLT2 genes in primary lung cancers and their metastatic lesions. Ninety-six autopsy samples (35 primary lung cancers, 35 corresponding normal lung tissues, 10 metastatic liver lesions, and 16 metastatic lymph nodes) from 35 patients were analyzed for SGLT1 and SGLT2 expression by reverse transcription (RT)-polymerase chain reaction (PCR). There were no significant differences in the level of expression of either gene between the primary lung cancers and normal lung tissues. The level of SGLT1 expression in the metastatic lesions and primary lung cancers did not differ significantly. The level of SGLT2 expression was, however, significantly higher in the metastatic lesions of both the liver and lymph node than in the primary lung cancers. These results suggest that SGLT2 plays a role in glucose uptake in the metastatic lesions of lung cancer.

Association between expression of the MRP3 gene and exposure to platinum drugs in lung cancer.

To investigate the roles played by the multidrug resistance-associated protein (MRP1) homologues MRP3 and MRP4 in resistance to platinum drugs, we examined steady-state levels of mRNA for both MRP3 and MRP4 in normal lung and lung cancer specimens as well as peripheral mononuclear cells (PMN) after platinum drug exposure. MRP3 and MRP4 gene expression levels were monitored in the PMN of 10 previously untreated lung cancer patients within 24 hr after carboplatin (CBDCA) administration. Expression levels for both genes were also examined in 80 autopsy samples (40 primary tumors and 40 corresponding normal lung tissues) from 40 patients with lung cancer. MRP3 and MRP4 gene expression levels were assessed by quantitative reverse transcription-polymerase chain reaction. MRP3 expression levels in the PMN rose rapidly within 24 hr after administration of CBDCA, whereas MRP4 expression levels remained the same. Furthermore, MRP3 expression levels in normal lung and tumor tissues from autopsy samples that had been exposed to platinum drugs while the patients were alive were significantly higher than those in unexposed tissues, but again MRP4 expression levels remained the same. These results suggest that platinum drugs and/or the physiological stress response to xenobiotics induce expression of the MRP3 gene.

[A case of lung adenocarcinoma showing diffuse air-space consolidation with idiopathic interstitial pneumonia].

Routine chest radiography demonstrated abnormal opacities in the right lower lung field of a 54-year-old man with idiopathic interstitial pneumonia. A high-resolution chest CT scan showed diffuse air-space consolidation in the right lower lung with replacement of a honeycomb area. The diagnosis was adenocarcinoma, and a right lower lobectomy was performed. Histopathologic examination showed moderately differentiated adenocarcinoma and the pathological stage was T3 N0 M0 (Stage IIB). About 1 year later, the cancer recurred with diffuse air-space consolidation in the whole of the right lung and the left middle and lower lung, which resulted in the patient's death. It was difficult to discriminate between an acute change for the worse of idiopathic interstitial pneumonia and a recurrence of lung cancer on the basis of the CT findings in this patient. It is important to elucidate the CT features of lung cancer associated with idiopathic interstitial pneumonia.

Carboplatin AUC and gamma-glutamylcysteine synthetase gene expression in peripheral mononuclear cells of lung cancer patients.

BACKGROUND: To investigate the association between glutathione-related enzymes and carboplatin (CBDCA) dose, we examined gene expression levels for both subunits of gamma-glutamylcysteine synthetase (heavy; gamma-GCSh, light; gamma-GCS1) in peripheral mononuclear cells (PMN) of lung cancer patients before and after CBDCA administration. MATERIALS AND METHODS: PMN and plasma samples were obtained from 10 advanced non-small lung cancer patients before and after CBDCA administration. We analyzed the gene expression levels by reverse transcription-polymerase chain reaction. RESULTS: Gamma-GCSh expression levels in PMN increased within 24 hours after CBDCA administration, whereas gamma-GCS1 expression levels did not. However, the actual area under the concentration curve (AUC) of CBDCA did not correlate with gamma-GCSh expression at 24 hours or the increased ratio of gamma-GCSh expression in PMN. CONCLUSION: Expression of gamma-GCSh is induced by CBDCA, however, CBDCA AUC is not a determinant for the increased expression levels of gamma-GCSh in PMN.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1998)].

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and analyzed some characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In these 18 institutions around the entire Japan, 532 strains of presumably etiological bacteria were isolated mainly from the sputa of 438 patients with lower respiratory tract infections during the period from October in 1998 to September in 1999. MICs of various antibacterial agents and antibiotics were determined against 85 strains of Staphylococcus aureus, 100 strains of Streptococcus pneumoniae, 96 strains of Haemophilus influenzae, 75 strains of Pseudomonas aeruginosa (non-mucoid strains), 6 strains of Pseudomonas aeruginosa (mucoid strains), 38 strains of Moraxella subgenus Branhamella catarrhalis, 26 strains of Klebsiella pneumoniae etc., and the susceptibilities of 517 strains were assessed except for those strains that died during transportation. S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus: MRSA) accounted for 60.0%. Vancomycin (VCM) and arbekacin (ABK) showed the most potent activities against MRSA. But one of MRSA showed resistance to ABK with the MIC of 64 micrograms/ml. The sensitive strains of MRSA to VCM have decreased. The frequency of penicillin (PC)-intermediate S. pneumoniae (PISP) + PC-resistant S. pneumoniae (PRSP) have increased in 46.0% for 1998 comparatively from 30.9% of 1997's. But PRSP decreased, and PISP increased into 39.0% of 1998 years from 19.8% of 1997's. Panipenem (PAPM), imipenem (IPM) and faropenem (FRPM) showed the most potent activities against S. pneumoniae with MIC80s of 0.125 microgram/ml or below. Against H. influenzae and M. (B.) catarrhalis, almost all the drugs showed good activities. The sensitive strains of them against ceftazidime (CAZ) decreased in 1997, but those have increased in 1998. Inversely, the susceptibility of them against cefotiam (CTM) had been higher in 1997, but those have been lower in 1998. Tobramycin (TOB) showed the most potent activity against P. aeruginosa (both mucoid and nonmucoid strains). All drugs except ampicillin (ABPC) were active against K. pneumoniae. A quite few of K. pneumoniae showed low susceptibilities. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. The examination of age distribution indicated that the proportion of patients with ages over 70 years was 48.6% of all the patients showing a slight increase in every year. About the proportion of diagnosed diseases as follows: Bacterial pneumonia was the most frequent with 40.2%. The ratio of it has increased slightly, and the increased rate was 10% in patients with ages over 70 years compared with the results in 1997. Chronic bronchitis have decreased slightly with 27.6% in 1998. Number of strains isolated from patients before administration of antibiotics were more than those after administration of them in chronic bronchitis, but these were almost same number in bacterial pneumonia. Administration of antibiotics has changed the results of the frequency of isolation of bacterial species. Bacterial isolations before administration of antibiotics were as follows: S. pneumoniae 26.7%, H. influenzae 23.8%, S. aureus 13.3% and M. (B.) catarrhalis 10.8%. The frequencies of S. aureus decreased after antibiotics administration over 15 days, but the frequencies of P. aeruginosa (both mucoid and non-mucoid) was not affected. The frequencies of P. aeruginosa was 45.5% after administration over 15 days. The frequencies of S. pneumoniae decreased upon administration of antibiotics, these were only 4.5% over 15 days. The frequencies of H. (

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1998). III. Secular changes in susceptibility].

Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Echerichia coli, Klebsiella spp. and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 9 hospitals during June 1998 to May 1999, and the results were compared with those obtained during the same period from 1990 to 1997 in uncomplicated UTIs and complicated UTIs. Among E. faecalis strains, those with low susceptibilities to almost drugs have increased in the latest period. All 5 S. aureus strains isolated from uncomplicated UTIs were the most susceptible to gentamicin (GM). Over 50% of S. aureus strains isolated from complicated UTIs were susceptible to GM, and on the contrary the resistant strains have increased with the MIC90 of 256 micrograms/ml or above. Among S. aureus strains isolated from complicated UTIs, those with low susceptibilities to arbekacin (ABK) have increased in the latest period compared to those during period of 1996-1997, and the MIC90s of them have changed into the lower state from 1 microgram/ml in 1996-1997 to 4 micrograms/ml in 1998. S. aureus strains have continued high susceptibilities to vancomycin (VCM). The susceptibilities to minocycline (MINO) of E. coli showed MIC90: 4 micrograms/ml in 1997, but those have returned in the latest period in uncomplicated UTIs. The MIC90s of ofloxacin (OFLX) to E. coli isolated from uncomplicated and complicated UTIs have been lower 2-3 classes in the latest period than those in 1997. Among Klebsiella spp. strains isolated from uncomplicated UTIs, those with low susceptibilities to almost cephems had increased in 1997, but few of them were detected in the latest study. The sensitive strains of P. aeruginosa to almost drugs have increased during the latest period. The MIC50s of cefozopran (CZOP) and OFLX against P. aeruginosa were the best in our history. The sensitive strains of P. aeruginosa to ceftazidime (CAZ) have increased and its percentage was 30%. Piperacilline (PIPC), cefoperazone (CPZ), GM and OFLX resistant P. aeruginosa strains have increased in the latest period.

[CPT-11 (irinotecan)--evidence from molecular and pharmacological studies and clinical applications].

Irinotecan (CPT-11) is a derivative of the chemotherapeutic agent Camptothecin. CPT-11 inhibits the nuclear enzyme topoisomerase I. It has demonstrated a broad spectrum of antitumor activity in preclinical tumor model systems. Significant advances have been made toward the understanding of the pharmacokinetics and schedule dependency of this agent. The principal dose limiting toxicities are diarrhea and leukopenia. CPT-11 has been evaluated using a variety of dosing schedules. Two main schedules have been studied and produce similar activity and side-effects: the "Japanese-North American" one where CPT-11 is given at a weekly dose of 100-150 mg/m2 for 4 consecutive weeks followed by a 2 week rest period, and the "European" one-350 mg/m2 every 21 days. CPT-11 has demonstrated significant clinical activity in the treatment of patients with gastrointestinal, pulmonary, gynecologic, and lymphoid malignancies. A recent randomized trial demonstrated a survival advantage in metastatic non-small cell lung cancer and previously untreated metastatic colorectal cancer. Further study of this agent to determine its role in combination chemotherapeutic regimens is currently underway.

[Activities of antimicrobial agents against 5,180 clinical isolates obtained from 26 medical institutions during 1998 in Japan. Levofloxacin--Surveillance Group].

The surveillance study was conducted to determine the antimicrobial activity of fluoroquinolones (ofloxacin, levofloxacin, ciprofloxacin, tosufloxacin) and other 20 antimicrobial agents against 5,180 clinical isolates obtained from 26 medical institutions during 1998 in Japan. The resistance to fluoroquinolones was remarkable in Enterococci, methicillin-resistant staphylococci and Pseudomonas aeruginosa from UTI. However, many of the common pathogens such as Streptococcus pneumoniae including penicillin-resistant isolates, methicillin-susceptible Stahylococcus aureus, Moraxella catarrhalis, the family of Enterobacteriaceae, Haemophilus influenzae including ampicillin-resistant isolates have been kept to be susceptible to fluoroquinolones. About 90% of P. aeruginosa isolates from RTI were susceptible to fluoroquinolones. In conclusion, the results from this surveillance study suggest that fluoroquinolones are useful in the treatment of various bacterial infections including respiratory infections.