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We conducted a retrospective, hospital-based study of patients who were diagnosed with bacterial endophthalmitis on admission to the Department of Ophthalmology, Hiroshima University Hospital, between January 1999 and December 2003. Thirty eyes of 30 patients were identified. Of these patients, 19 eyes had postoperative endophthalmitis, 8 eyes had penetrating trauma and 3 eyes were infected from an endogenous source. All of the patients underwent immediate three-port pars plana vitrectomy. Vitreous specimens of diabetic patients demonstrated a significantly higher incidence of positive bacterial culture. Diabetic vitreous appeared to be a good medium for culture. Visual acuity of hand motion or less at the latest follow-up visit was associated with the presence of diabetes. Prompt treatment with vitrectomy and intra-vitreal antibiotics is crucial for patients with bacterial endophthalmitis, especially if they are diabetic.

Recently, the alteration of peripheral T cells has become a focus of attention in research on Crohn's disease (CD). To examine the characteristics of peripheral T cells in CD patients, we analyzed the expression of a memory T cell marker (CD45RO(Bright)CD3+) and the cytokine production by peripheral helper and cytotoxic T cells in patients with CD. With the use of monensin to prevent the secretion of cytokines under stimulation, we measured the count of intracellular cytokine-positive cells for production of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-4, IL-6, IL-10, and granulocyte-macrophage colony stimulating factor (GM-CSF) in the peripheral T cell population using flow-cytometry. The counts of lymphocytes, T cells, and helper T cells in patients with CD were significantly lower than in normal volunteers. Although no difference in the counts of lymphocytes, total T cells, helper and cytotoxic T cells was observed, the counts of intracellular cytokine producing helper T cells in IFN-gamma, TNF-alpha or GM-CSF were significantly higher in active cases than in quiescent cases. These results suggest that stable CD patients are immunosuppressive, and activation of some kinds of T-cells, especially Th1-associated cytokine producing T-cells, correlate with disease progression. Th1-associated cytokine analysis of peripheral T cells may be one of the useful markers to evaluate the activeness of Crohn's disease.

In major systemic inflammation such as severe peritonitis, various pro-inflammatory cytokines, such as TNF-alpha, IL-1 beta and IL-6, play important roles in the development of multiple organ dysfunction syndrome (MODS). The purpose of this study was to investigate the outflow of pro-inflammatory and anti-inflammatory cytokines from the efferent mesenteric lymphatic vessels under peritonitis. Mesenteric lymph samples were collected from adult male rats at 2, 4, 6, 8 and 10 hr after an intraperitoneal injection of zymosan at a dosage of 0.1 mg/g (non-lethal dose) or 0.5 mg/g (lethal dose). Blood samples were obtained at 10 hr after zymosan administration. The amounts of drained TNF-alpha and IL-6 in the lymph peaked at 2-4 hr and 4-8 hr after zymosan administration, respectively. The amounts of drained IL-10 in the lymph gradually increased until 10 hr. The amounts of drained TNF-alpha and IL-10 in the mesenteric lymph were significantly correlated with the dosage of zymosan. In conclusion, under intraperitoneal inflammation, pro-inflammatory cytokines (TNF-alpha and IL-6) increased in the mesenteric lymph and were drained into circulation. IL-10, one of the anti-inflammatory cytokines, also increased in the mesenteric lymph after several hours' delay and its increase was remarkable in several inflammations. These findings suggested that the gut might be one of the pro-inflammatory and anti-inflammatory cytokine-generating organs under peritonitis. The lymph-drained amounts of each cytokine under peritonitis are considered to differ with the time or severity of inflammation, which may cause different conditions in patients due to the imbalance of pro-inflammatory and anti-inflammatory cytokines.

The intrinsic resistance of methicillin-resistant Staphylococcus aureus (MRSA) is frequently explained by the production of an additional penicillin-binding protein (PBP), which is encoded by the mecA gene. The mec regulator genes, mecR1 and mecI, was identified in mecA-carrying Staphylococcus aureus N315. Between February and March, 1993, 179 clinical MRSA isolates were collected from institutions in Hiroshima prefecture. According to serological types of coagulase, enterotoxins, and toxic shock syndrome toxin-1 (TSST-1) productions, these strains were classified into 6 groups. In 53 strains chosen from all groups, mec regulatory gene distributions were divided into two groups; one with whole regulatory genes and another with the lacking region, including 3'-partial region of the mecR1 gene and mecI gene. This same deletion was detected across the different groups, suggesting that the deletion occurred at the ancestral strain before branching according to coagulase or enterotoxin productions. The strains with this lacking region showed a high-level of resistance to methicillin, while the strains with whole regulatory genes consisted of low and high levels of resistant strains. The highly resistant strains with whole regulatory genes were found to harbor a point mutation in the mecI gene. The basal levels of mecA gene transcription were elevated in the strains with the lacking region or the mecI point mutations. These data suggest that deletion or mutation of the mecI gene, the repressor on the mecA gene, might play an important role in methicillin resistance in clinical isolates of MRSA.

The purpose of this study was to assess the point at which the postoperative infection has occurred in order to decide upon the proper duration of prophylactic antibiotic use. Another goal of this study was to determine whether prediction for the development of postoperative infections in major surgery such as esophagectomy should be the same as that in routine gastroenterological surgery. Twenty-five patients who underwent transthoracic esophagectomy and 127 patients who underwent gastrectomy were studied. On the third day after gastric surgery, the body temperature of patients who developed an infection was higher than that of the patients who did not develop an infection. The relative changes in peripheral white blood count (WBC), and C-reactive protein (CRP) concentration on the third and fourth days were more predictive of the development of infection than the absolute values. Almost all patients with systemic inflammatory response syndrome (SIRS) on the third day after gastric surgery developed an infection. On the other hand, the incidence of SIRS in patients who did not develop an infection was high on both the third and fourth days after esophageal surgery. It was nearly impossible to predict who would develop an infection in esophageal surgery. The high incidence of postoperative infections, and their significant consequences justify planned successive postoperative antibiotic use in esophageal surgery.

An adult living related partial liver transplantation was performed on a 49 year old female with terminal hepatic failure due to primary biliary cirrhosis (PBC). The donor was her 53 year-old sister. A sufficient volume of graft tissue was obtained, which comprised 1.5% of the body weight of the recipient. The recipient had an excellent recovery without any major complications, and was discharged 35 days after the operation. At 15 months after the operation, the patient has shown no signs of rejection while using FK506 and prednisolone as immunosuppressants. The progression of symptomatic PBC can be predicted, and the timing of the transplantation can be easily determined. In addition, the results of liver transplantation for PBC are good. Therefore, adult living related partial liver transplantation is an excellent treatment for primary biliary cirrhosis.

The aim of this study was to evaluate the characteristics of the polymorphonuclear leukocyte (PMN) function after surgical stress. We investigated Mac-1 expression and superoxide generation by peripheral PMNs and serum granulocyte-colony stimulating factor (G-CSF) concentrations in 15 patients who underwent either gastrectomy (n = 8) or esophagectomy (n = 7). The serum G-CSF rapidly increased within 24 hours after operation. The maximum levels of serum G-CSF in the cases of esophagectomy were about 5-8 fold those of gastrectomy, although the increases in PMN counts within 24 hours of esophagectomy were lower than those after gastrectomy. Mac-1 expression and superoxide generation by PMN counts and serum G-CSF. After esophagectomy, Mac-1 expression on peripheral PMNs remained elevated through the 7th day after operation, while superoxide generation by PMNs in response to PMA declined to below preoperative levels after the 3rd day. These results suggest that, after major surgery such as esophagectomy, there is a discrepancy between Mac-1 expression and superoxide generation by the peripheral PMN despite a high level of serum G-CSF.

Resistance patterns against various antimicrobial agents including beta-lactams, aminoglycosides, tetracyclines, fluoroquinolones, macrolides were examined for 58 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated at Hiroshima University Hospital from April to November 1992. All the MRSA strains produced type II-coagulase but not beta-lactamase. Regarding aminoglycoside-modifying enzymes, 7 strains (12%) appeared to be producing aminoglycoside 4',4"-adenyltransferase AAD(4',4") encoded by aadD without coproduction of bifunctional aminoglycoside 6'-acetyltransferase/2"-phosphotransferase AAC(6')/APH(2") encoded by aacA-aphD (referred to as tobramycin-resistant type, TOBr). The remaining 51 strains (88%) were phenotypically producers of both enzymes (i.e., mix-resistant type, Mixr). AAD(4',4"), encoded by aadD which was reported to be closely linked with bleomycin (BLM)-resistance determinant, could be seen in 100% MRSA strains and ca. 90% strains expressed AAC(6')/APH(2"). BLM endowed Mixr-type but not TOBr-type MRSA strain with enhanced resistance to arbekacin (ABK) dose-dependently, presumably by modifying the production of AAC(6')/APH(2"). The manifestation of ABK-resistant phenotype by Mixr-type MRSA required the coexistence of BLM. Therefore, ABK must be administered carefully to cure MRSA infection in patients who have been treated with BLM.

Resistance patterns against 25 antimicrobial agents consisting of beta-lactams, aminoglycosides, tetracyclines, fluoroquinolones, macrolides and etc. were examined for 69 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated at Hiroshima University Hospital from July 1991 to April 1992. Regarding overall resistance (the percentage of highly and moderately resistant strains), the following antimicrobial agents were no more effective chemotherapeutics for MRSA infections (%resistance): methicillin (100), flomoxef (100), kanamycin (100), tobramycin (100), amikacin (100), isepamicin (100), gentamicin (78), dibekacin (100), ofloxacin (99), levofloxacin (99), temafloxacin (99), erythromycin (100), clarithromycin (100), tetracycline (93), minocycline (93) and fosfomycin (100). Further spread of arbekacin-resistant strain, which was isolated in April 1991, into a clinical environment could not be recognized during the period covered in the present study. All the MRSA strains were resistant either constitutively (26 strains) or inducibly (43 strains) to macrolide-lincosamide-streptogramin B (MLS) antibiotics. When expression is constitutive, the strains are resistant to all MLS antibiotics. In contrast, 16-membered macrolide (i.e., jasamycin), lincomycin and mikamycin B escape resistance in the strains with a typical inducible resistance overcome in the presence of 14-membered macrolides by a translational attenuation mechanism. Three of 4 beta-lactamase-positive strains, however, can not be classified in these two resistance groups, being exclusively resistant to mikamycin B. The strains grown in the presence of any inducing MLS antibiotic became susceptible to mikamycin B even in the inducer-free culture.

Resistance patterns against 24 antimicrobial agents were examined for 50 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated at Hiroshima University Hospital during the period October 1990 and July 1991. Overall resistance (the percentage of highly and moderately resistant strains) to the antimicrobial agents is summarized as follows: methicillin 100%, flomoxef 100% (beta-lactams); kanamycin 94%, tobramycin 94%, amikacin 100%, isepamicin 94%, gentamicin 80%, dibekacin 94%, arbekacin 2% (basic oligosaccharide group/aminocyclitols); ofloxacin 96%, temafloxacin 96%, levofloxacin 96% (fluoroquinolones); erythromycin 98%, clarithromycin 98%, josamycin 30% (macrolides); vancomycin 0% (glycopeptide); tetracycline 94%, minocycline 94% (tetracyclines); fosfomycin 100%; mikamycin B 30%, nosiheptide 0% (peptide); rifampicin 2% (ansamycin); streptomycin 2% (basic oligosaccharide group); chloramphenicol 2%. Arbekacin resistance was observed in one case: the cross resistance was complete among the aminocyclitol antibiotics tested in this study and streptomycin, probably due to the ribosomal alteration.

Resistance patterns against 23 antimicrobial agents were examined for 42 strains of methicillin-resistant Staphylococcus aureus (MRSA). Thirty-four strains were isolated at Hiroshima University Hospital during 1984-1990 and 8 strains were collected in Tokushima city in 1986. Overall resistance to the antimicrobial agents in clinical use is summarized as follows: methicillin 100%, flomoxef 93% (beta-lactams); kanamycin 98%, tobramycin 88%, amikacin 83%, isepamicin 81%, gentamicin 60%, dibekacin 64%, arbekacin 0% (aminocyclitol aminoglycosides); ofloxacin 31%, TA-167 33% (fluoroquinolones); erythromycin 100%, clarithromycin 100%, josamycin 71% (macrolides); vancomycin 0% (glycopeptide); tetracycline 43%, minocycline 31% (tetracyclines); fosfomycin 93%. The MRSA strains remained susceptible to the non-clinical peptide group of antibiotics except for mikamycin B: mikamycin A 2%, mikamycin B 69%, nosiheptide 0%, bottromycin A2 0%, bottromycin D-1 0%, bottromycin D-2 0%. Since April 1990, the MRSA strains isolated at Hiroshima University Hospital showed a tendency to acquire resistance to tetracyclines and fluoroquinolones and to lose mikamycin B-resistance. As of August 1990, none of the MRSA strains isolated at Hiroshima University Hospital was resistant to vancomycin and arbekacin.

Concomitant with the extensive use of antibiotics, the number of multiple antibiotic-resistant strains has been increasing. Since resistance is mainly mediated by R plasmids, we undertook to investigate the characteristics of R plasmid-determined beta-lactamase in 6 Gram-negative rods. The beta-lactamase produced by each organism was classified by its substrate: type P which attacks penicillins, type C which attacks cephalosporins, and type C/P which attacks both penicillins and cephalosporins. Though the chromosomally mediated beta-lactamase of almost all Gram-negative rods is classified as type C, R plasmid-mediated beta-lactamase is almost equally active against both penicillins and cephalosporins. Therefore, we suggest that type C/P beta-lactamase was mediated by R plasmids in Gram-negative rods which already produced chromosomally mediated type C beta-lactamase. The strains which produced type C/P beta-lactamase tended to be more resistant to antibiotics than the other beta-lactamase producing strains. Among type C/P strains, the sensitivity to cephalosporins varied with the bacterial species, whereas all these strains were highly resistant to penicillins. Even for piperacillin, which is stable to cephalosporinase, the MIC at which the cumulative percentage of strains inhibited was 50% (MIC50) was over 50 micrograms/ml in all strains tested.

In this study 214 strains of Staphylococcus aureus were isolated from clinical specimens on the surgical ward from 1983 to 1988 and in addition, 62 airborne strains were collected in the operating room. Highly methicillin-resistant strains of S.aureus (H-MRSA, MIC greater than 100 micrograms/ml) not detected in 1983 showed a significant increase in frequency by 1987 accounting for about 60% of MRSA (MIC greater than or equal to 12.5 micrograms/ml). Countermeasures instituted in 1987 such as the use of disinfectant chlorhexidine alcohol significantly decreased the frequency of MRSA and H-MRSA isolates in 1988. In our study of coagulase type, MRSA type IV strains were predominant until 1984, whereas after 1986 type II was prevalent. All airborne strains collected in the operating room were methicillin-sensitive S.aureus, with type VII currently epidemic. We therefore concluded that cross infection with MRSA took place on the surgical ward rather than in the operating room.