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Background The aim of this study was to evaluate the efficacy and feasibility of preoperative chemotherapy with S-1 plus cisplatin in patients with initially unresectable locally advanced gastric cancer. Methods We enrolled patients with initially unresectable locally advanced gastric cancer because of severe lymph node metastases or invasion of adjacent structures. Preoperative chemotherapy consisted of S-1 at 80 mg/m2 divided in two daily doses for 21 days and cisplatin at 60 mg/m2 intravenously on day 8, repeated every 35 days. If a tumor decreased in size, patients received 1 or 2 more courses. Surgery involved radical resection with D2 lymphadenectomy. Results Between December 2000 and December 2007, 27 patients were enrolled on the study. No CR was obtained, but PR was seen in 17 cases, and the response rate was 63.0%. Thirteen patients (48.1%) had R0 resections. There were no treatment related deaths. The median overall survival time (MST) and the 3-year overall survival (OS) of all patients were 31.4 months and 31.0%, respectively. Among the 13 patients who underwent curative resection, the median disease-free survival (DFS) and the 3-year DFS were 17.4 months and 23.1%, respectively. The MST and the 3-year OS were 50.1 months and 53.8%, respectively. The most common site of initial recurrence after the R0 resection was the para-aortic lymph nodes. Conclusions Preoperative S-1 plus cisplatin can be safely delivered to patients undergoing radical gastrectomy. This regimen is promising as neoadjuvant chemotherapy for resectable gastric cancer. For initially unresectable locally advanced gastric cancer, new trials using more effective regimens along with extended lymph node dissection are necessary.

Energy distributions of secondary charged particles were calculated in tissue substitutes irradiated by neutrons from 0.14 to 65 MeV, using the Particle and Heavy Ion Transport code System. The calculations were compared with experimental data measured by tissue equivalent proportional counters (TEPC). It is found that the calculated distributions of the lineal energy, y, generally agree well with the measured ones for neutrons from several 100 keV to 15 MeV. In the case of 40 and 65 MeV neutron irradiations, wall effects of TEPC should be considered and the fluence of alphas is underestimated by the calculations. Integrated dose contributions of the secondary charged particles are generally in good agreement with those of the measured ones.

BackgroundPoorly defined cohorts and weak study designs have hampered cross-cultural comparisons of course and outcome in schizophrenia.AimsTo describe long-term outcome in 18 diverse treated incidence and prevalence cohorts. To compare mortality, 15- and 25-year illness trajectory and the predictive strength of selected baseline and short-term course variables.MethodHistoric prospective study. Standardised assessments of course and outcome.ResultsAbout 75% traced. About 50% of surviving cases had favourable outcomes, but there was marked heterogeneity across geographic centres. In regression models, early (2-year) course patterns were the strongest predictor of 15-year outcome, but recovery varied by location; 16% of early unremitting cases achieved late-phase recovery.ConclusionsA significant proportion of treated incident cases of schizophrenia achieve favourable long-term outcome. Sociocultural conditions appear to modify long-term course. Early intervention programmes focused on social as well as pharmacological treatments may realise longer-term gains.

The classification of 'Manic-depressive illness(MDI)' has been changing in this several years greatly. MDI is recently named as a 'mood(affective) disorder' according to the ICD and DSM diagnostic system. Since 1990, with ICD-10(WHO), and 1994, with DSM-IV(APA), practitioners have had at their disposal two(practically compatible) classifications of mental disorders containing operational criteria for diagnosis, and helpful in guiding clinical and therapeutic approach. In ICD-10, mood disorder belongs to the F3 category, and there are seven subcategories which were divided in to subclasses. The two other subclasses of 'F06.3 organic mood disorder' 'F41.2 mixed anxiety and depressive disorders' were set up additionally.

To determine the optimum pouch reconstruction after total gastrectomy, we conducted a randomized trial to compare the usefulness between PR and PI in terms of quality of life.Thirty patients younger than 70 years of age were selected and randomly classified into the following 2 groups: pouch and Roux-en-Y (PR; n = 15) and pouch and interposition (PI; n = 15). In each subject, the postoperative symptoms, food intake in a single meal, body weight, serum nutritional parameters, endoscopy, emptying time of the gastric substitute, and gallstone formation were evaluated.There were no significant differences in terms of the postprandial symptoms, food intake, body weight, and serum nutritional parameters until 2 years postoperative. Endoscopy showed a tendency of food stasis in the PR group, although this was not significant. The gastric emptying test in the PR group indicated that the retention capacity was slightly superior to that in the PI group.The impact of the duodenal passage on symptoms and nutrition could not be ascertained.

There have been many reports proposing some advantages of pylorus-preserving gastrectomy for gastric ulcer compared to the conventional distal gastrectomy. However, it is not clear whether similar results will be obtained from the patients with early gastric cancer.Of 50 patients with early gastric cancer, 25 underwent pylorus-preserving gastrectomy under strict criteria and the other 25 underwent distal gastrectomy with Billroth I anastomosis by the same surgeon. The subjects were then interviewed and examined periodically to assess symptoms, food intake, body weight and serum nutritional parameters. Endoscopy and a radioisotope gastric emptying test was performed 1 year after the operation.Many of the patients with pylorus-preserving gastrectomy complained of gastric fullness after meals, resulting in poor food intake; a significant between-group difference was found up to 1 year after the operation. A low incidence of reflux gastritis and slow gastric emptying were confirmed in the patients after pylorus-preserving gastrectomy.Pylorus-preserving gastrectomy has advantages over distal gastrectomy in terms of the avoidance of dumping syndrome and protection against duodeno-gastric reflux. However, more time was necessary for improved gastric fullness or food intake. Pylorus-preserving gastrectomy should be applied in younger patients with early gastric cancer expecting long survival.

Most acute psychotic episodes are regarded as indicators of schizophrenia. We developed an algorithm for the treatment of such episodes. In Japan, psychiatrists tend to prescribe two or more neuroleptics at once, but it is thought that using a single neuroleptic is better, and the algorithm we report is based on this view. Since there are few reports on how to choose and use a single neuroleptic in Japan, our method is simply an example, with insufficient scientific support. It will need to be revised in future.

In order to evaluate antimicrobial activities of clarithromycin (CAM), minimum inhibitory concentrations (MICs) of CAM and control drugs were determined against clinical isolates that were obtained from outpatients in 1994 and 1996. The results are summarized as follows; 1. It was not showed that CAM-resistant strains were increasing among Staphylococcus spp., beta-streptococci, Moraxella subgenus Branhamella catarrhalis, Haemophilus influenzae, Bordetella pertussis, Campylobacter jejuni subsp. jejuni, Chlamydia trachomatis and Mycoplasma pneumoniae. It appeared that resistances to CAM and macrolides (MLs) were increasing among Streptococcus pneumoniae and Peptostreptococcus spp. 2. The drug susceptibility patterns to MLs were similar and detection frequencies of induced resistant strains that were resistant to only 14-membered ring MLs including CAM and constitutive resistant strains that were resistant to 14 and 16-membered ring MLs were high among Streptococcus pneumoniae and Peptostreptococcus spp. It appears that MLs-resistance systems are linked to each other, and that this was a cause of increasing MLs-resistance among these bacterial species. 3. Notwithstanding of antibiotic resistance problems, CAM is still useful since it maintains strong antimicrobial activities against M. (B.) catarrhalis, B. pertussis, C. jejuni subsp. jejuni, C. trachomatis and M. pneumoniae, and it controls arginate producing abilities of mucoide strains of Pseudomonas aeruginosa.

Long-term mortality and morbidity was evaluated in 267 patients with a minimum follow-up of 10 yr and the physical status, graft function and quality of life in 15 patients with a functioning graft surviving for over 20 yr were reviewed. Actual patient and graft survival rates were 80.2% and 51.1% at 10 yr (n = 267) and 56.4% and 32.7% at 20 yr (n = 55), respectively. Although the rate of graft failure due to rejection was 4 times higher than that of patient death within 10 yr, it decreased to the level of patient death in the second decade. Dominant causes of death in patients with graft surviving for over 10 yr were hepatic failure due to viral hepatitis and malignancies. In 15 patients with graft currently surviving beyond 20 yr, while all patients have excellent graft function, malignancy occurred in 5, viral hepatitis in 3, aseptic necrosis in 3, and diabetes mellitus in one patient. No patient has suffered cardiovascular complications. Despite a high rate of morbidity, they show a satisfying status of rehabilitation (full time working 11/ 15, 73.3%). In order to attain more improved QOL in patients with long-term surviving renal transplant, close follow-up aiming at diminution of complications is required throughout the period after transplantation.

The authors modified the operative procedures used in pouch and interposition (PI) reconstruction in an attempt to improve the surgical results after a total gastrectomy, because a randomized controlled trial had revealed that the clinical assessment of PI was quite poor, even though it is a physiological route. In most of the treated patients, the gastric emptying test revealed delayed emptying, and an X-ray video film showed folding and twisting of the jejunal conduit between the pouch and duodenum, which disturbed the transmission of the nutrition. Modified PI (m-PI) was performed by decreasing the length of the jejunal conduit and widening the jejunal pedicle to preserve the blood and nerve supply. The m-PI group showed a lower incidence of symptoms, a greater food intake, and a greater weight recovery than the PI group. The gastric emptying test also revealed an acceptable degree of emptying. We conclude that the m-PI reconstruction is more useful for improving the postoperative quality of life than the previously used method of PI reconstruction.

The mechanism of pleural fibrosis in malignant and inflammatory pleural effusion remains unclear. We measured the levels of type III procollagen N-terminal amino peptide (PIIIP) and type IV collagen 7S in patients who had pleural effusion and lung carcinoma, and in others who had inflammatory diseases (parapneumonic and tuberculous pleuritis). The PIIIP level and the PIIIP/type IV collagen 7S ratio in patients with malignant pleural effusion were significantly lower than those in patients with inflammatory pleural effusion (p0.01), but the levels of type IV collagen 7S did not differ. The ratio of PIIIP to type IV collagen 7S was higher in patients with tuberculous pleuritis than in those with parapneumonic pleuritis (p0.05). These data indicate that pleural fibrotic adhesion may be accelerated in inflammatory pleural effusion because of elevated production of type III collagen; basement membrane injury in malignant and inflammatory pleural effusion may be caused by similar damage. We conclude that a high level of PIIIP and a high PIIIP/type IV collagen 7S ratio may indicate the presence of inflammatory pleuritis, and that the latter may indicate the presence of tuberculous pleuritis.

The reservoir and transit capacity of the post-gastrectomy jejunal pouch was evaluated, using a radioisotopic method, to examine the relationship of the gastric emptying to postprandial symptoms and to the food intake status.Thirty-seven patients who had undergone total gastrectomy for cancer (Roux-Y reconstruction, 8; Hunt- Lawrence pouch and Roux-Y, 15; pouch interposition, 5; modified pouch interposition, 9) were retrospectively studied. Based on the percent retention in the gastric substitute, the emptying curves were classed as showing delayed, intermediate, and rapid emptying types.All of the patients with pouch reconstruction showed either delayed or intermediate emptying. High frequency of the sensation of epigastric fullness, nausea, or vomiting was demonstrated in the patients with delayed emptying (p0.01). The patients with delayed emptying showed poor food intake compared to those with intermediate emptying (p0.05). Given the X-ray video film and endoscopic findings, the delayed emptying was thought to be due to poor drainage of the efferent loop resulting from the post-operative adhesions.The present study revealed that delayed emptying is associated with postprandial symptoms and with poor food intake. The examination of gastric emptying is useful in evaluating or predicting the postoperative status.

In order to evaluate antimicrobial activity of arbekacin (ABK), coagulase-type and minimum inhibitory concentrations (MICs) of ABK and other drugs were determined against 700 strains of methicillin-resistant Staphylococcus aureus (MRSA) that were obtained in our laboratory from 1990 to 1996, 7 years. The results are summarized as follows; 1. The MIC-distributions of ABK against 100 strains of MRSA obtained yearly did not show stochastically significant differences. 2. The coagulase-type distributions showed differences over the years. Coagulase-type II strains increased and type IV strains decreased, and MIC-distributions of ABK and other drugs were different according to coagulase-types. 3. The detection frequencies of ABK-resistant strains (MIC of ABK:or = 12.5 micrograms/ml) were 2.0 approximately 8.0% through the years. The frequency reported in 1980 was equal to the frequency obtained in 1992 approximately 1993 in a nationwide survey. Coagulase-types II, IV and VII that were ABK-resistant strains were frequently obtained, and most of ABK-resistant strains were also highly resistant to gentamicin.

In order to evaluate antimicrobial activity of cefodizime (CDZM), minimum inhibitory concentrations (MICs) of CDZM and control drugs were determined against clinical isolates collected from nation-wide medical institutions and in our laboratory from September to December of 1992 and from September to December of 1995. The results are summarized as follows: 1. Bacterial species with no or few strains resistant to CDZM included Streptococcus pyogenes, Haemophilus influenzae, Citrobacter koseri, Proteus mirabilis and Neisseria gonorrhoeae. The range of MIC values of CDZM against Klebsiella pneumoniae was spread. Other strains, Streptococcus pneumoniae, Moraxella subgenus Branhamella catarrhalis, Escherichia coli, Citrobacter freundii, Enterobacter spp., Serratia marcescens, Proteus vulgaris, Morganella morganii, Providencia spp., Peptostreptococcus spp. and Bacteroides fragilis group were resistant to cephems including CDZM. 2. The MIC90's of CDZM were 0.05 approximately 3.13 micrograms/ml against Streptococcus spp., H. influenzae, M. (B.) catarrhalis, E. coli, Klebsiella spp., P. mirabilis, N. gonorrhoeae and Peptostreptococcus spp. obtained in 1995 that were frequently found in daily treatment of infections. It appears that the effectiveness of CDZM was still relatively high against community-acquired infections. 3. Among H. influenzae isolates included imipenem (IPM)-resistant and norfloxacin (NFLX)-resistant strains. The MIC-range of CDZM against strains collected in 1995 including IPM-resistant and NFLX-resistant strains wasor = 0.025 approximately 0.1 microgram/ml, and MIC90 against these strains was 0.05 microgram/ml. CDZM showed strong antimicrobial activities against H. influenzae strains resistant to carbapenems and new-quinolones.

The purpose of the study was to evaluate the potential of dynamic Gd-DTPA-enhanced MR imaging in assessing of the function of transplanted kidneys. Dynamic MR imaging was performed using the GRASS pulse sequence in 21 subjects (56 examinations), and in each examination 30 images were obtained after a bolus injection of Gd-DTPA. Imaging findings including signal increase and/or signal drop in cortex, signal drop in medulla, and signal drop in calyces were utilized for the evaluation of renal function. Renal function was also evaluated using the following parameters: Ta, time between the initial observation of signal increase in cortex and signal drop in medulla. Tb, time between the initial observation of signal drop in medulla and in calyces; Tc, Ta + Tb, and Max. C/M, maximum ratio of signal intensity between cortex and medulla among 30 images. In the group of patients with normal graft function (Ccror = 60ml/min), all imaging findings were observed. In the group of patients with mild graft dysfunction (30ml/minor = Ccr60ml/min), all imaging findings but signal drop in cortex were observed. The time parameters of Ta, Tb, and Tc were significantly larger, and Max. C/M was significantly smaller than those observed in the group with normal graft function. In the group of patients with severe graft dysfunction (Ccr30ml/min), almost none of the findings were observed. The investigation in patients in the postoperative state revealed a close correlation of the imaging findings and the values of parameters with changes in graft function over time. The results indicated the usefulness of the method in semiquantitative evaluation of graft function, including that of patients in postoperative state. This study suggests that dynamic Gd-DTPA-enhanced MR imaging could be a valuable method for the management of transplanted kidneys.

To evaluate antimicrobial activities of tosufloxacin (TFLX), minimum inhibitory concentrations (MICs) of TFLX and other drugs were determined against clinical isolates that were obtained in our laboratory from February of 1993 to January of 1994 (Period I), and from February of 1995 to January of 1996 (Period II). The results are summarized as follows: 1. Compared to MIC90's reported by others for TFLX in the 1980's, those obtained by us against beta-streptococci, Streptococcus pneumoniae, Peptostreptococcus spp., Haemophilus influenzae and Salmonella spp. were similar to, but those obtained against other bacteria were higher than those reported values. 2. Detection frequencies of resistant strains to TFLX were compared between Period I and Period II. MIC90's of TFLX against Staphylococcus spp., Morganella morganii, Providencia spp., Pseudomonas aeruginosa, beta-streptococci, S. pneumoniae and Peptostreptococcus spp. were lower in Period II than in Period I. TFLX-insensitive or -resistant H. influenzae were found among strains isolated in either of the Periods. 3. Most of the TFLX-resistant Gram-negative organisms tested were also resistant to other NQ's. 4. TFLX showed strong antimicrobial activities against penicillin-resistant S. pneumoniae.

In order to evaluate the antimicrobial activity of meropenem (MEPM), minimum inhibitory concentrations (MICs) of MEPM and control drugs were determined against clinical isolates from blood and cerebrospinal fluid that were obtained from January, 1993 to December, 1994. The results are summarized as follows; 1. The MIC-range, 50% MIC (MIC50) and 90% MIC (MIC90) of MEPM were equal to those of imipenem (IPM) and panipenem (PAPM) against Streptococcus pneumoniae including benzylpenicillin (PCG)-insensitive or -resistant S. pneumoniae, Streptococcus agalactiae and Listeria monocytogenes which are Gram-positive strains, and were stronger than those of ampicillin (ABPC) and cefotaxime (CTX). 2. The MIC-range, MIC50 and MIC90 of these 3 drugs of carbapenems (MEPM, IPM and PAPM) were different against Escherichia coli and Haemophilus influenzae which are Gram-negative strains. The MIC90 of MEPM wasor = 0.025 microgram/ml and those of IPM and PAPM were 0.2 microgram/ml against E. coli. The MIC90 of MEPM was 0.1 microgram/ml, that of IPM was 25 micrograms/ml and that of PAPM was 6.25 micrograms/ml against H. influenzae. Thus, the antimicrobial activity of MEPM was stronger than those of IPM and PAPM. The MIC90's of IPM and PAPM against H. influenzae were high with the MIC of IPM at 12.5 approximately 25 micrograms/ml and the MIC of PAPM at 3.13 approximately 12.5 micrograms/ml against 3 IPM-resistant strains among 17 isolates. 3. The MIC90 of ABPC was 0.39 microgram/ml and that of CTX was 0.1 microgram/ml against 20 strains of S. pneumoniae including 6 strains of PCG-insensitive or resistant S. pneumoniae. The MIC90 of ABPC and CTX were higher than those of 3 carbapenem drugs. There were E. coli of 8 strains with ABPC-high resistance (the MIC of ABPC was100 micrograms/ml) and 2 strains for which MIC of CTX were 0.39 microgram/ml and 3.13 micrograms/ml. It was found that 29.4% of H. influenzae were beta-lactamase producing strains. 4. It appeared that antimicrobial activities of carbapenems, particularly MEPM were strong against clinical isolates from blood and cerebrospinal fluid. MEPM will be first choice drug by empiric therapy in infections including sepsis and purulent meningitis.

To examine the antimicrobial activity of clarithromycin (CAM) against strains clinically isolated from outpatients in 1994, minimum inhibitory concentrations (MICs) were determined for CAM and the control drugs. The results were as follows; 1. MIC50 and MIC90 of CAM were similar to those investigated in 1980's against many bacterial species. 2. CAM showed strong antimicrobial activities against beta-lactamase producing Moraxella subgenus Branhamella catarrhalis, Bordetella pertussis, Campylobacter jejuni subsp. jejuni and Peptostreptococcus spp. 3. It appears that resistance to MLs including CAM is increasing among Streptococcus pneumoniae.

In order to evaluate antimicrobial activity of meropenem (MEPM), minimum inhibitory concentrations (MICs) of MEPM and control drugs were determined against clinical isolates in 1993. The results were as follows; 1. Antimicrobial activities of MEPM against Gram-positive bacteria were stronger than those of cephems (CEPs), were approximately equal to those of panipenem (PAPM), and were weaker than those of imipenem (IPM). 2. Carbapenems showed strong antimicrobial activities against Enterobacteriaccae, glucose non-fermentative Gram-negative rods and Bacteroides fragilis group that were multiple drug resistant including the third generation CEPs. Antimicrobial activities of MEPM against these organisms were stronger than those of IPM and PAPM. 3. MIC-ranges of MEPM against Enterobacteriaceae and Haemophilus influenzae were lower than those of IPM and PAPM. We observed that MEPM had better permeability into the cells of H. influenzae, higher affinities to 3 to 5 different penicillin-binding protein and high stability against beta-lactamase than those of IPM and PAPM.

We report a pulmonary blastoma lacking sarcomatous features in 33-year-old woman. Abnormal shadow was detected in the right upper field in a routine chest X-ray film. The preoperative imaging films showed a 4 x 4 cm, well-circumscribed solid tumor in S3 of the right lung. The preoperative clinical diagnosis of primary lung cancer was considered. The operative findings showed that an elastic hard tumor, 5 cm in diameter, was localized in S3 of the right lung and partially contacted the middle lobe. Right upper and middle lobe resection was performed with lymph node dissection. The postoperative diagnosis was pulmonary blastoma, well differentiated fetal lung (= WDFA). It is considered that the degree of the malignancy of WDFA is lower and the prognosis of WDFA is better than conventional pulmonary blastoma (= biphasic blastoma). There are not available treatments except for surgical resection. It is suggested that it necessary to collect as many cases as possible, to make definite classifications and to examine the clinical course and prognosis of pulmonary blastoma.

In order to investigate antimicrobial activities of clavulanic acid/ticarcillin (CVA/TIPC) against Escherichia coli, Enterobacter spp. and Pseudomonas aeruginosa in 1992 and 1994, beta-lactamase activities were analyzed and minimum inhibitory concentrations (MICs) were determined including those of the control drugs. The results are as follows; 1. Compared to a report in 1980, the MIC distributions of CVA/TIPC against E. coli and P. aeruginosa did not show large differences. We found, however, that CVA/TIPC-resistant strains increased among Enterobacter spp. 2. Almost all of CVA/TIPC-resistant strains of Enterobacter spp. were also resistant to cephems and new quinolones, thus they were multiple drug resistant. 3. CVA/TIPC showed strong antimicrobial activities against penicillinase producing E. coli.

In order to evaluate antimicrobial activity of cefepime (CFPM), minimum inhibitory concentrations (MICs) of CFPM and other drugs were determined against clinical isolates that were obtained in 1994. 1. CFPM showed a wide antibacterial spectrum against Staphylococcus spp. and glucose non-fermentative Gram-negative rods ((G)NF-GNR). Antimicrobial activities of CFPM against Staphylococcus spp. were stronger than those of ceftazidime (CAZ) and somewhat stronger than those of cefotaxime (CTX), and antimicrobial activity of CFPM against Pseudomonas aeruginosa was same as that of CAZ. 2. Antimicrobial activities of CFPM against almost all of Enterobacteriaceae were stronger than those of CAZ and CTX. And CFPM showed strong antimicrobial activities against CAZ-resistant Escherichia coli, Citrobacter freundii and Enterobacter spp. 3. Antimicrobial activities of CFPM were weaker than those of CAZ against some of strains of Klebsiella oxytoca, beta-lactamase high producing strains of Moraxella subgenus Branhamella catarrhalis and than those of CTX against beta-lactamase high producing strains of Prevotella spp. 4. The feature of new cephems was demonstrated in that CFPM had wider antibacterial spectrum than cephems of previous genenations against Staphylococcus spp. and (G)NF-GNR and CFPM showed strong antimicrobial activities against almost all of oxacephem-resistant Enterobacteriaceae.

In order to investigate antimicrobial activities of clavulanic acid/amoxicillin (CVA/AMPC) against freshly isolated clinical strains obtained in 1995, beta-lactamase activities and minimum inhibitory concentration (MICs) were determined including those of the control drugs. The results are summarized as follows; 1. Detection frequencies of beta-lactamase producing strains were as follows: methicillin-susceptible Staphylococcus aureus subsp. aureus (MSSA, 90.0%), Haemophilus influenzae (22.0%), Moraxella subgenus Branhamella catarrhalis (100.0%), Escherichia coli (100.0%), Klebsiella pneumoniae subsp. pneumoniae (100.0%) and Neisseria gonorrhoeae (14.0%). It appeared that beta-lactamases produced by these strains were mostly penicillinase or enzyme of similar that. 2. Antimicrobial activities of CVA/AMPC against beta-lactamase producing strains were stronger than those of AMPC, and MIC90 of CVA/AMPC against benzylpenicillin (PCG)-insensitive or resistant Streptococcus pneumoniae was lower than those of sultamicillin, cefaclor and cefpodoxime. 3. CVA showed strong beta-lactamase inhibitory effect against M.(B.) catarrhalis of direct and indirect pathogenicity. We can expect CVA/AMPC to negate or decrease the influence of indirect pathogenicity.

A comparison was made for frequencies of isolation o glucose non-fermentative Gram-negative rods ((G)NF-GNR) from clinical specimens during a period from July, 1986 to June, 1987 (the first period) and that from January, 1994 to December, 1994 (the second period). Also, minimum inhibitory concentrations of principal drugs were determined against these isolates. The obtained results are summarized as follows: 1. Thirty four (34) species of (G)NF-GNR were found from 35,200 clinical specimens in the two periods. Numbers of strains of (G)NF-GNR obtained were 4,575 during the first period and 4,704 during the second period, thus no significant difference existed in numbers of strains isolated in the two periods. 2. Among the 34 species to which the 4,704 strains were classified into, Pseudomonas aeruginosa comprised 68.4%, Stenotrophomonas maltophilia 6.9%, Acinetobacter baumannii 5.6%, Burkholderia cepacia 3.1%, Acinetobacter Iwoffii 2.6%, Alcaligenes xylosoxidans subsp. xylosoxidans 2.4%, Flavobacterium indologenes 1.7%, Pseudomonas putida 1.1%, Acinetobacter junii 1.1% and Moraxella subgenus Moraxella lacunata 0.9%. When these frequencies of isolation were compared with those in the first period, it was found that B. cepacia decreased significantly (P0.01) and that S. maltophilia increased significantly (P0.001). 3. MIC determinations revealed multiple drug resistance strains in many different species of bacteria. Minocycline, however, were active against many such strains, and ofloxacin was found to have strong antibacterial activity against some strains.

A study was done to determine susceptibilities of Haemophilus influenzae that were obtained in our laboratory in 1994 to new quinolones (NQ) and other drugs. The results were as follows; 1. Among the 300 isolates, the detection frequency of NQ-resistant strains was 8.7% (26 strains), including isolates from chronic lower respiratory tract infections (22 strains) and those from middle meatus of nose (2 strains), etc. NQ-resistant strains were not isolated from children. 2. The cross resistance was studied for different NQs against NQ-resistant strains. Clavulanic acid/amoxicillin, cefteram, cefpodoxime, cefditoren, cefodizime (CDZM) and cefpirome showed strong antimicrobial activities against NQ-resistant strains. MIC90 of CEPs against all isolated strains including NQ-resistant strains and beta-lactamase producers was low. And the MIC90 of CDZM wasor = 0.025 microgram/ml, which was the lowest among all the antibiotics tested. 3. We found 47 strains (15.7%) of beta-lactamase producers among the 300 isolates, the frequency of beta-lactamase producing strains was high among strains obtained from children.

In order to evaluate antimicrobial activity of norfloxacin (NFLX), minimum inhibitory concentration (MICs) of NFLX and control drugs were determined against clinical isolates from ocular infections that were obtained in our laboratory from July, 1993 to December, 1994. The results are summarized as follows; 1. Compared to MIC distributions of NFLX against clinical isolates from ocular infections studied in 1986 and 1987, the MIC80 of NFLX against Corynebacterium spp., Enterobacter spp., Serratia spp., Burkholderia cepacia, Flavobacterium spp., Alcaligenes spp. increased 8 times. Almost all of NFLX-resistant strains among them were ofloxacin (OFLX)-resistant, new quinolones resistant strains, and a part of them were aminoglycosides, beta-lactams-resistant as well, thus all of these strains were multiple drug resistant. 2. MIC of NFLX against Pseudomonas aeruginosa were lower than that of OFLX. 3. NFLX showed strong antimicrobial activities against so-called "particular bacteria" including Staphylococcus aureus subsp. aureus, Moraxella spp., Haemophilus spp., and P. aeruginosa from ocular infections. And MIC80 of NFLX against these bacteria was 0.05-1.56 microgram/ml. We observed that NFLX eye drops was administered so that concentrations above the MIC against these clinical isolates were maintained.

In order to evaluate antimicrobial activity of cefmenoxime (CMX), minimum inhibitory concentrations (MICs) of CMX and control drugs were determined against clinical isolates from patients of sinusitis that were obtained in our laboratory from October of 1993 to March of 1994. The results are summarized as follows; 1. CMX showed strong antimicrobial activities against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella subgenus Branhamella catarrhalis that were 3 major aerobic bacteria from sinusitis. Antimicrobial activities of CMX against benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) and PCG-resistant S. pneumoniae (PRSP) were stronger than those of ampicillin (ABPC), and these strong activities suggested that CMX might have strong antimicrobial activities against beta-lactamase producing H. influenzae and M. (B.) catarrhalis. 2. Antimicrobial activities of CMX against microaerophiles, Streptococcus constellatus, Streptococcus intermedius and Gemella morbillorum and against Peptostreptococcus spp., from chronic sinusitis and odontogenic maxillary sinusitis, were stronger than those of most of the control drugs. 3. The MIC90's of CMX against isolates from patients of sinusitis wereor = 0.025-0.39 micrograms/ml. These values were lower than transitional concentrations in mucous membrane of maxillary sinus obtained when "1% CMX nasal solution" was used with nebulizer. It appears likely that sufficient concentrations exceeding MICs against main organisms would be obtained by nebulizer treatment using CMX nasal solution.

Antimicrobial activities were examined for sulbactam/ampicillin (SBT/ABPC) against clinically isolated microbial strains in 1987, 1990, 1994. Besides, the beta-lactamase productivity and MICs of these strains were measured, and the following conclusions were obtained. 1. The ratio of beta-lactamase producing strains were 90% of methicillin (DMPPC)-susceptible Staphylococcus aureus subsp. aureus (MSSA), about 80% of DMPPC-resistant S. aureus (MRSA), 100% of Escherichia coli, Klebsiella pneumoniae subsp. pneumoniae and Proteus mirabilis, 95% of Moraxella subgenus Branhamella catarrhalis and 15-20% of Haemophilus influenzae. Several kinds of beta-lactamase productivity were observed. 2. Antimicrobial activities of SBT/ABPC against beta-lactamase producing strains of MSSA, M. (B.) catarrhalis, H. influenzae, and almost all of Enterobacteriaceae were stronger than those of ampicillin (ABPC) and piperacillin (PIPC), but antimicrobial activities of SBT/ABPC were weak against MRSA and cephems (CEPs)-resistant strains detected in some of Enterobacteriaceae. 3. It appeared that benzylpenicillin (PCG)-insensitive Streptococcus pneumoniae (PISP) or PCG-resistant S. pneumoniae (PRSP) and CEPs-resistant Escherichia coli increased year by year. 4. Antimicrobial activities of SBT/ABPC were strong against Streptococcus pyogenes, S. pneumoniae, M. (B.) catarrhalis and H. influenzae including beta-lactamase producing strains. Additionally, beta-lactamase inhibiting effect of SBT was observed against beta-lactamase produced by S. aureus and K. pneumoniae which demonstrate indirect pathogenicity. Thus, SBT/ABPC is an injectable antibiotic that is expected to demonstrate clinical usefulness, especially as the first line drug for the respiratory tract infections that are community-acquired.

We examined beta-lactamase productions by clinically isolated strains of bacteria. The results were as follows; 1. It appears that beta-lactamases produced by strains of five species of Staphylococcus spp. are mostly penicillinase (90%). Source of beta-lactamase producing strains of Haemophilus influenzae (23%) and all of Moraxella subgenus Branhamella catarrhalis: strains (100%) are "HighLow producer" strains. 2. A large proportion of beta-lactamase producing strains of Enterobacteriaceae and Bacteroides fragilis group appeared to be "High producer" 3. beta-lactamase producing abilities are different among glucose non-fermentative Gram-negative rods. It appears that some of the strains appeared to be "High producers".

Antibacterial activities of cefetamet (CEMT) against clinically isolated strains from patients with community acquired respiratory tract infections were compared to those of other oral beta-lactam antibiotics in the period from January to March 1994. The following results were obtained. 1. CEMT showed strong antibacterial activities against three major pathogens causing community acquired respiratory tract infections, Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae. However, antibacterial activities of CEMT against benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) and PCG-resistant S. pneumoniae (PRSP) were slightly weaker than of those of some the reference antibiotics. 2. No MIC value changes of CEMT were observed from year to year against Moraxella subgenus Branhamella catarrhalis and Klebsiella pneumoniae.

To examine the antimicrobial activity of cefditoren (CDTR) against strains clinically isolated from outpatients at this hospital from November, 1993 to February, 1994, the minimum inhibitory concentrations (MICs) were determined including those of the control drugs. The results were as follows: 1. CDTR showed strong antimicrobial activities against Staphylococcus aureus subsp. aureus, Streptococcus pyogenes and Streptococcus pneumoniae. The MICs of CDTR against benzylpenicillin-insensitive or -resistant S. pneumoniae distributed in the lowest concentration range even compared to those of the control drugs. 2. CDTR showed strong antimicrobial activities against Haemophilus influenzae, Moraxella subgenus Branhamella catarrhalis, Escherichia coli, and Klebsiella spp. The MIC of CDTR against CEPs-resistant E. coli was lower than those of most control drugs. 3. Since the microbes described above the major pathogens for the community-acquired infections, CDTR will be effective against infectious diseases transmitted at outpatient visits.

In order to investigate antibacterial activities of new quinolones (NQs) against a number of clinical isolates obtained in our laboratory during a period from February, 1993 to January, 1994, minimum inhibitory concentrations (MICs) were determined using most of the NQs available in the market as of December, 1993. The obtained results are summarized as follows: 1. Noticeable differences were observed among the antibacterial activities of 8 different NQs tested against Gram-positive bacteria, i.e., there were large differences in their MIC distributions. Some differences were also observed among different NQs in ratios of NQ-resistant strains among Staphylococcus spp. From these results, it seems necessary to further study tolerance mechanisms of these Gram-positive bacteria toward different NQs and also to examine possible differences in antibacterial activities among different NQs against Gram-positive bacteria in clinical settings. 2. MIC distributions against Gram-negative bacteria were also different among the 8 NQs tested. Though elevated MICs were observed against NQ-resistant Gram-negative bacteria in many cases, and somewhat higher, though not exceedingly high, MIC values than those against NQ-sensitive bacteria were found in other cases, patterns of MIC values against different NQ-resistant Gram-negative bacteria were similar for all of the 8 NQs tested. This may explain the fact that most of NQ-resistant Gram-negative bacteria showed similar resistant patterns to the 8 NQs tested. 3. Among the NQ-resistant bacteria, were found Haemophilus influenzae and Neisseria gonorrhoeae strains. Ratios of resistant strains were approximately 10% or lower for the former and approximately 20% for the latter. 4. With MICs of ampicillin and cefaclor used as control, it appears that benzylpenicillin (PCG)-insensitive or PCG-resistant Streptococcus pneumoniae (PISP or PRSP) and CEPs-resistant Escherichia coli are increasing.

In order to examine antimicrobial activities of fosfomycin (FOM), the minimum inhibitory concentrations (MICs) of FOM and those of control drugs were determined against Streptococcus pneumoniae and Haemophilus influenzae isolated from sinusitis patients from September to November, 1993, and the following results were obtained. 1. Among 50 S. pneumoniae strains tested, there were 10 strains (20.0%) of benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) and 2 strains (4.0%) of PCG-resistant S. pneumoniae (PRSP); but the MIC distributions of FOM among the PISPs and the PRSPs were almost identical to those among the PCG-susceptible S. pneumoniae (PSSP). 2. There were 12 strains (24.0%) of beta-lactamase producing strains among 50 strains of H. influenzae tested, but the FOM's MIC distribution among these strains was almost identical to that among beta-lactamase non-producing strains. 3. The results obtained on the MIC90s of FOM against S. pneumoniae and H. influenzae suggest that the nebulization treatment with FOM nasal preparation satisfies the condition "above the MIC".

In order to evaluate antimicrobial activity of ciprofloxacin (CPFX), minimum inhibitory concentrations (MICs) of CPFX and other drugs were determined against clinical isolates that were obtained in our laboratory from January to December of 1991, and of 1993. The results are summarized as follows: 1. CPFX-resistant strains were on the increase in various strains, compared to those in the early 1980s. However, many of CPFX-resistant strains were multi-drug resistant including beta-lactams. In addition, they showed cross resistance to other fluoroquinolone agents. 2. MIC distribution of other drugs suggested that there were increased frequencies of benzylpenicillin (PCG)-insensitive Streptococcus pneumoniae (PISP) and CEPs-resistant Escherichia coli. However, MIC distribution of CPFX to these resistant strains were in a relatively low range. 3. When isolates of 1991 were compared to those of 1993, we confirmed that CPFX-resistant strains decreased among certain bacteria such as Staphylococcus aureus. Also we confirmed that fewer CPFX-resistant strains were found among bacteria that may be highly related to infections encountered in daily medical care.

To investigate antibacterial activities of isepamicin (ISP), MICs of ISP as well as other aminoglycosides (AGs) were determined against many strains of Gram-negative bacilli that were clinically isolated in 1993. 1. No ISP-resistant strains were observed among isolates of Escherichia coli, Citrobacter diversus, Klebsiella spp., Enterobacter spp. or Proteus mirabilis. 2. ISP-resistant strains were observed among isolates of Citrobacter freundii, Serratia spp., Proteus vulgaris, Morganella morganii, Providencia spp. and Pseudomonas aeruginosa. The frequency of resistant strains in each species, however, was lower for ISP than other AGs. 3. When MIC90s were compared, antibacterial activities of ISP determined in this study were quite similar to those determined during the drug's development period (1980's) in Japan, suggesting no increase in the number of ISP-resistant strains over the years. 4. The number of clinically isolated Gram-negative bacilli resistant to multiple drugs are increasing in from year to year Japan. Our results in this study suggest that antibacterial activities of ISP may be potent enough against such Gram-negative bacilli resistant to multiple drugs.

In 1899, Kraepelin, E. proposed the concept of affective disorder as "Das manisch-melancholische Irressin". The classification of MDI had changed in several years. WHO developed the ICD-10 in 1990. In the F3 category of ICD-10, it is stated that MDI is a "mood (affective) disorder". In that category, there are seven categories which are divided in to several subclasses. The episodic mood disorders are "manic episode", "bipolar affective disorder", "depressive episode" and "recurrent depressive disorder". In contrast to these groups, the persistent mood disorders are "dysthymia" and "cyclothymia". In addition, there are two other items, "organic mood disorder" (F06.3) and "mixed anxiety and depressive disorders" (F41.2).

Antimicrobial activity of cefuroxime axetil (CXM-AX) was compared with those of other cephem antibiotics against clinically isolated strains obtained mainly from outpatients of our center in a period from January to September of 1990 and 1993. Minimum inhibitory concentrations were determined and the following results were obtained. 1. The results suggested that, compared with reports of studies conducted with clinical isolates in early 1980's, MIC80 of CXM were equal to or lower against Staphylococcus spp., Streptococcus pyogenes, Escherichia coli, Klebsiella spp., Proteus mirabilis, Haemophilus influenzae, Moraxella subgenus Branhamella catarrhalis, Neisseria gonorrhoeae, Peptostreptococcus spp., and Propionibacterium acnes, except for Streptococcus pneumoniae, MIC80 which was slightly higher. 2. MIC90 of comparator drugs reflected those of new resistant organisms recently appeared, such as benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP), cephem-resistant E. coli and Klebsiella spp., new quinolone-resistant H. influenzae and N. gonorrhoeae. Methicillin-resistant Staphylococcus aureus (MRSA) was detected also from specimens of community acquired infections. From the nature of MRSA detected in those situations MRSA appeared to present a continuing problem. 3. MIC90 against strains obtained from patients with community acquired infections was a good index of increases of multidrug-resistant organisms in the past. Therefore, the determination of MIC90 is important in examining changes with time of sensitivities or resistances of clinically isolated strains to antimicrobial drugs. 4. Antimicrobial activities of CXM against recent clinical isolates showed the existence of problems as mentioned above. However, MIC of CXM as well as those of comparator drugs indicated that antimicrobial activities of CXM against Staphylococcus spp., Streptococcus spp., H. influenzae appeared to be relatively strong, and it is concluded that cefuroxime axetil still is one of the clinically useful oral antimicrobial drugs in the 1990's.

beta-Lactamase production and activities in sputa of patients with community-acquired lower respiratory tract infections (LRTI) were determined and following results were obtained: 1) Suspected causative organisms frequently isolated were H. influenzae and Streptococcus pneumoniae. Similar results were previously reported. 2) Various beta-lactamase producing indigenous bacteria were detected. In many cases these indigenous beta-lactamase producing strains were isolated even when suspected causative bacteria were not beta-lactamase producers. 3) beta-Lactamase activities were detected from 61.5% of the sputa tested. Remaining activities of antibiotics added to the sputa were highly correlated with detection of beta-lactamases produced by suspectedly causative and indigenous strains and with presence of beta-lactamase activities in the sputa. Sulbactam/cefoperazone was stable in sputa than other antibiotics tested. 4) We concluded that the beta-lactamase produced by indigenous strains can be one of the factors of indirect pathogenicity in the community-acquired LRTI.

Patients with gastric cancer aged 70 years or over were divided into 3 age groups (70-74, 75-79, 80 years or over) and were compared with patients aged 60-69 years, (which is the age group with the highest incidence of stomach cancer) with regard to the incidence of postoperative complications. In addition, factors which might be associated with increased mortality were investigated. There were no significant differences with regard to the incidence of postoperative complications (16-21%) or the mortality rate (0-3%, within 30 days after surgery) between the various age groups. However, the incidence of those complications which later proved fatal was higher in those aged 75 years or over. Factors associated with the development of complications in each age group were the type of surgical technique used, the operation time, and the severity of hemorrhage during surgery. The prognosis for gastric resection was poor in patients aged 80 years or over. Our findings indicated that curative resections should be performed for gastric cancers in the elderly if the general physical condition of the patients permits. A more conservative approach is desirable when the general condition is not favorable.

In order evaluate antimicrobial activities of cefodizime (CDZM), minimum inhibitory concentrations (MIC's) of CDZM and other control drugs were determined against various clinical isolates, that were sent to our center from nation-wide medical institutions or were isolated and identified in our laboratory from various specimens of infected patients. The followings are a summary of the results: 1. Bacterial species with no or few strains resistant to cephems including CDZM included Streptococcus pyogenes, Haemophilus influenzae, Citrobacter diversus, most of Klebsiella pneumoniae and Proteus mirabilis. Some strains of Klebsiella oxytoca were resistant to cephems increases in beta-lactams resistant Streptococcus pneumoniae and cephem resistant Escherichia coli seemed likely. Among Citrobacter freundii, Enterobacter spp., Serratia marcescens, Proteus vulgaris, Morganella morganii and Providencia spp. belonging to a category of so-called "mildly toxic bacteria", high portions of the strains examined were resistant to cephems including CDZM and these strains were also resistant to new quinolones, thus they showed multiple drug resistance. 2. MIC90's of CDZM against Streptococcus spp., H. infleunzae, Moraxella subgenus Branhamella catarrhalis, E. coli, Klebsiella spp. and P. mirabilis, frequently found in daily treatment of infections, were less thanor = 0.025 to 1.56 micrograms/ml. This indicates that CDZM would be expected to have enough antibiotic activity in infections caused by above mentioned bacteria. However, cautions are needed in the treatment of infections by beta-lactam resistant S. pneumoniae, cephem resistant E. coli and cephem resistant K. oxytoca with CDZM. 3. Among the above mentioned "mildly toxic bacteria", many multiple drug resistant strains exist. Therefore, we evaluated an usefulness of concomitant use of CDZM with aminoglycosides in the treatment of infections by these bacteria, using other reports which indicates the usefulness in vitro and in vivo. 4. Antibacterial activities of CDZM we observed in this study seem to indicate that CDZM concentrations in infected areas are maintained at above MIC levels for relatively long periods of time.