Latitudinal variation in top-down and bottom-up control of a salt marsh food web.

The shrub Iva frutescens, which occupies the terrestrial border of U.S. Atlantic Coast salt marshes, supports a food web that varies strongly across latitude. We tested whether latitudinal variation in plant quality (higher at high latitudes), consumption by omnivores (a crab, present only at low latitudes), consumption by mesopredators (ladybugs, present at all latitudes), or the life history stage of an herbivorous beetle could explain continental-scale field patterns of herbivore density. In a mesocosm experiment, crabs exerted strong top-down control on herbivorous beetles, ladybugs exerted strong top-down control on aphids, and both predators benefited plants through trophic cascades. Latitude of plant origin had no effect on consumers. Herbivorous beetle density was greater if mesocosms were stocked with beetle adults rather than larvae, and aphid densities were reduced in the "adult beetle" treatment. Treatment combinations representing high and low latitudes produced patterns of herbivore density similar to those in the field. We conclude that latitudinal variation in plant quality is less important than latitudinal variation in top consumers and competition in mediating food web structure. Climate may also play a strong role in structuring high-latitude salt marshes by limiting the number of herbivore generations per growing season and causing high overwintering mortality.

Variation in tolerance and resistance to the leafhopper Empoasca fabae (Hemiptera: Cicadellidae) among potato cultivars: implications for action thresholds.

The potato leafhopper, Empoasca fabae (Harris) (Hemiptera: Cicadellidae), is an emerging pest of potato and insecticide applications to control this insect have increased in recent years. Based on field observations of leafhopper-crop dynamics, however, currently recommended action thresholds seem to be overly conservative. As a result, we initiated two experiments designed to quantify the impact of leafhoppers on potato yield, and determine how the magnitude of this effect changes among cultivars. In experiment 1, leafhoppers were manipulated (control versus insecticide-treated plots) on 17 potato varieties. In experiment 2, three cultivars (Superior, Atlantic, and Snowden) were planted representing early-, mid-, and late-season maturing lines, and six insecticide spray regimes were imposed (early-, late-, and full-season applications at high and low rates). In both experiments, leafhopper abundance, plant damage, and potato yield were measured. Overall, leafhoppers reduced yield in control plots by 15.7% relative to insecticide-treated plots. Leafhopper impact, however, varied among cultivars; a significant effect of leafhoppers on yield was detected in 6, 12, and 59% of cultivars tested in each of three trials. Of the 44 cases in which leafhoppers exceeded action thresholds, yield loss was only documented in 13 cases. Data from these experiments provide evidence that such variable effects ofleafhoppers on yield are explained by cultivar-specific resistance and tolerance traits. Our results suggest that potato growers can accept higher leafhopper densities than current thresholds recommend, particularly when cultivating resistant and/or tolerant varieties.

Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor drug.

S-1 is a novel oral fluorouracil antitumor drug that combines three pharmacological agents: tegafur (FT), which is a prodrug of 5-fluorouracil (5-FU); 5-chloro-2,4-dihydroxypyridine (CDHP), which inhibits dihydropyrimidine dehydrogenase (DPD) activity; and potassium oxonate (Oxo), which reduces gastrointestinal toxicity. Phase I and early Phase II clinical trials have already been completed. On the basis of the results of these trials, 80 mg/m2/day, given daily in two divided doses after breakfast and supper, a 28-day consecutive oral regimen is recommended. In this study, we investigated the pharmacokinetics of 5-FU, intact FT, CDHP, and Oxo, after administration of S-1, at a standard dose of 80 mg/m2/day, in advanced cancer patients. Twelve patients were recruited to the study; 5 patients with gastric cancer, 4 with colorectal cancer, and 3 with breast cancer. Among them, analysis was conducted on 12 patients for single administration and on 10 patients for consecutive administration. The initial dose of S-1 for each patient was determined according to his/her body surface area (BSA) as follows: for BSA < 1.25 m2, 80 mg/body/day; for 1.25 m2 < or = BSA < 1.5 m2, 100 mg/day; and for 1.5 m2 < or = BSA, 120 mg/day. For single administration, half of the standard dose was used. For 28-day consecutive administration, the standard dose was given daily in two divided doses. The average single dose per BSA was 35.9 mg/m2 (31.7-39.7 mg/m2). Pharmacokinetic parameters of plasma 5-FU were as follows: Cmax, 128.5 +/- 41.5 ng/ml; Tmax, 3.5 +/- 1.7 h; AUC(0-14), 723.9 +/- 272.7 ng x h/ml; and T(1/2), 1.9 +/- 0.4 h. In the 28-day consecutive regimen, there were no fluctuations in pharmacokinetics nor any drug accumulation. Because the pharmacokinetics of orally administered S-1 is almost similar to that of continuous i.v. infusion of 5-FU, we concluded that S-1 may improve patients' quality of life.

Nitric oxide induces a decrease in the mitochondrial membrane potential of peripheral blood lymphocytes, especially in natural killer cells.

Increased levels of nitric oxide (NO) at an inflammatory site may affect the biological activity of lymphoid cells. To investigate the effects of NO on the immune system, we measured the mitochondrial membrane potential (delta psi m) of the peripheral blood lymphocytes (PBL) cultured with a chemical NO donor. PBL from healthy volunteers were cultured with NOC18, a NO-generating compound, at various concentrations. The delta psi m of the PBL was measured by flow-cytometry using 3,3-dihexyloxacarbocyanine iodide (DiOC6(3)). NOC18 induced a decrease in the delta psi m of the PBL in a dose-dependent fashion, induced an increase in the levels of reactive oxygen species (ROS), and caused these cells to undergo apoptosis. Dual-color staining of the delta psi m and lymphocyte surface markers demonstrated that CD3-CD56+ natural killer (NK) cells were responsive to NO. Trolox, a vitamin E analog, partially reversed the NO-induced decrease in the delta psi m of the PBL. We showed that the delta psi m of peripheral NK cells were decreased by NO, which suggests that abundant NO at an inflammatory site may impair NK cell function.

Results of 1001 pancreatic resections for invasive ductal adenocarcinoma of the pancreas.

OBJECTIVE: To evaluate the recent results of pancreatic resection in patients with invasive ductal adenocarcinoma of the pancreas. DESIGN: Retrospective study. SETTING: Seventy-seven medical facilities belonging to the Japan Society of Pancreatic Surgery. PATIENTS: One thousand one patients who underwent a resection of the pancreas between January, 1, 1991, and December 31, 1994. MAIN OUTCOME MEASURES: Morbidity and survival after surgery for pancreatic cancer according to the modified TNM classification of the International Union Against Cancer. RESULTS: After pancreatic resection, the cumulative postoperative survival rates at 1 and 3 years were 44.5% and 10.3%, respectively. Patients with early-stage cancers had a more prolonged survival time, ie, the cumulative 3-year survival rates for patients with stage I or stage II cancers were 50.4% and 45.5%, respectively; the survival rates for patients with stage III and stage IVa and IVb cancers were 17.6%, 5.7%, and 0%, respectively. The survival rate for patients with N1 or N2 metastasis did not differ appreciably, and both groups had significantly better survival rates than patients with N3 metastasis (P < .001). A significant difference in the postoperative survival time of N1 metastasis was observed between patients with no lymph node dissection (mean survival, 326.4 days) and patients who received a lymph node dissection (D1) (mean survival, 478.2 days) (P < or = .01). CONCLUSIONS: The recent results of pancreatic resection for invasive ductal adenocarcinoma of the pancreas are generally unsatisfactory. Although the outcome of the patients with an N1 metastasis can be improved if they receive N1 lymph node dissection (D1), an extensive lymph node dissection in advanced cancers does not necessarily produce a favorable prognosis.

Changes in portal hemodynamics and hepatic function after partial splenic embolization (PSE) and percutaneous transhepatic obliteration (PTO).

Since April 1985, we have performed a multidisciplinary therapy consisting of partial splenic embolization (PSE), percutaneous transhepatic obliteration (PTO) or transileocolic vein obliteration (TIO), and endoscopic injection sclerotherapy (EIS) for patients with severe gastroesophageal varices and those with a portacaval shunt associated with portal hypertension. In this study, PSE and percutaneous transhepatic portography (PTP) were performed at the same time in seven liver cirrhosis patients with hypersplenism, gastroesophageal varices, or hepatocellular carcinoma. The changes in portal blood flow/pressure and hemodynamics were examined by a thermodilution method. The effects of PSE on blood biochemical parameters such as the platelet count, ICG R15, redox tolerance index (RTI), and oral glucose tolerance test (75 g OGTT) were also evaluated. PSE induced a decrease in the blood flow of the splenic artery and in the splenic vein pressure without decreasing the portal blood flow. The platelet count in the peripheral blood and the RTI increased significantly. These results suggest the possibility that PSE may reduce the potential perioperative risk in hepatocellular carcinoma complicated with liver cirrhosis.

A new peritoneal dissemination model established from the human pancreatic cancer cell line.

We established a new cell line, HPC-3P4a, with high peritoneal disseminated potential in nude mice. HPC-3P4a was derived from a human pancreatic carcinoma cell line (HPC-3) that had low capacity for peritoneal dissemination. HPC-3P4a developed peritoneal dissemination in 10 of 11 (90.9%) cases, whereas parental HPC-3 developed peritoneal dissemination in one of six (16.7%) cases. The metastatic foci in the peritoneum showed essentially the same histologic appearance of parental involvement. The tumorigenicity, motility, and adhesive activity of HPC-3P4a to the extracellular matrix were stronger than were those of the HPC-3. In FACS analysis, HPC-3P4a significantly increased the expression of alpha6 and alpha(v)beta5 integrins, while it decreased alpha2 integrin, hCD44H, and hCD44v 10, as compared with HPC-3. The VEGF production of HPC-3P4a was significantly lower than that of HPC-3. Analysis of gene macroarrays showed a variety of cytokines, interleukin, and other immunomodulatory, and their receptors were up-regulated and down-regulated on an mRNA level in HPC-3P4a cells, compared with HPC-3 cells. Intrasplenic injection of HPC-3P4a produced no liver metastasis. We named our original highly liver metastatic cell line HPC-3H4 (previously reported). This HPC-3H4 cell was established by repeated intrasplenic injection from parental cell HPC-3; thus, it developed high liver metastasis. Moreover, HPC-3H4 developed peritoneal dissemination by intra-abdominal injection. In contrast, HPC-3P4a did not develop liver metastasis by intrasplenic injection. These findings are very interesting and might suggest that the process of hematogenous metastasis differed from that of peritoneal dissemination. Thus, this cell line may be useful for investigating the mechanism of peritoneal dissemination in human pancreatic cancer.

The ratio of reduced glutathione/oxidized glutathione is maintained in the liver during short-term hepatic hypoxia.

Controversy persists as to whether reperfusion-induced injuries actually occur in the hepatocyte. The liver is the major source of glutathione, a scavenger of hydrogen peroxide. The aim of this study was to evaluate the sensitivity of the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) [GSH:GSSG] as an index of hepatic metabolic stress. A total of 121 rats were studied. The superior mesenteric vein (SMV) was occluded for 30 min, and this was followed by 0, 10, or 120 min of reperfusion. Total glutathione and GSSG levels in the liver, bile, and plasma were quantified, using glutathione reductase-coupled enzymatic assays. Results indicated that the hepatic GSH/GSSG ratio was maintained after an occlusion of the SMV, despite a decrease in adenosine triphosphate (ATP) level and energy charge potential. However, plasma levels of total glutathione and GSSG in the inferior vena cava increased after SMV occlusion and continued to increase after reperfusion. Biliary GSSG efflux decreased during 30-min occlusion of the SMV, and remained low even after reperfusion. The liver maintains homeostasis despite a decrease in biliary GSSG efflux, probably by secreting excess GSSG into the hepatic vein when the SMV is occluded. We conclude that the total amount of glutathione and GSSG in the plasma is directly correlated with oxidative stress in the liver.

Proximal gastrectomy and jejunal pouch interposition: evaluation of postoperative symptoms and gastrointestinal hormone secretion.

Reflux esophagitis, dumping syndrome and malnutrition are included in the postgastrectomy complications. To prevent or minimize such sequelae, proximal gastrectomy with an interposed jejunal pouch has been advocated as an organ-preserving surgical strategy to improve quality of life for the patients. Proximal gastrectomy was performed in 44 patients with tumors in the upper third of the stomach; 21 had reconstruction using jejunal pouch interposition between the esophagus and the remnant stomach (JP group), while 23 had reconstruction by esophagogastrostomy (EG group). Re-construction method was selected by each patient on the basis of the informed consent. Thirty-five patients had early gastric cancer. Postoperative courses of patients were reviewed in terms of symptoms, weight maintenance, nutritional status, blood chemistry values, endoscopic findings, and radiographic appearances after a barium meal. Concentrations of gastrointestinal hormones were measured in response to a test meal. The JP procedure permitted increased dietary volume. The JP group showed fewer severe postoperative symptoms than the EG group. After operation, all patients examined in both groups showed hypergastrinemia and all patients examined in the JP group showed hypersecretinemia. In proximal gastrectomy, the JP procedure improved patient's post-operative quality of life.

The enhanced effect of parenteral nutrition on hepatotoxicity.

Recent studies have demonstrated that enteral feedings are associated with decreased morbidity and mortality when compared with parenteral feedings. In this study, we hypothesized that (1) route of feeding affects morbidity and mortality in a model of drug-induced hepatotoxicity and (2) glutamine and polymyxin B, which have been reported to reduce bacterial translocation, attenuate this effect when TPN is used. Male virus-free Wistar rats were divided into six groups receiving: (1) ad libitum chow infused with intravenous (IV) saline (Chow), (2) standard total parenteral nutrition solution administered via gastrostomy (Enteral), (3) standard total parenteral nutrition infused via a central catheter (TPN), (4) standard TPN containing polymyxin B (TPN-PolyB), and (5) glutamine-enriched TPN (TPN-GLN). A final group of animals was not manipulated but harvested at time 0 to serve as controls. The dose of polymyxin B used in this study has previously been shown to significantly reduce bacterial translocation. After 4 d of feeding, all rats received 5% dextrose infusion after an intraperitoneal (IP) injection of acetaminophen (ACM). Rats were sacrificed 0, 6, and 24 h after ACM administration. The TPN group had a lower liver glutathione level after 6 and 24 h, greater levels of liver enzymes after 24 h, and a lower survival rate after 24 h compared with Chow. The Enteral group had less morbidity than TPN but greater morbidity than Chow. Addition of polymyxin B or glutamine had a minimal effect on morbidity or mortality when compared to the TPN group. We conclude that rats receiving IV nutrition have greater morbidity and mortality following a standard hepatic insult than chow-fed rats. We speculate that alteration of microsomal cytochrome P-450 or drug clearance may be related to the benefits of providing nutrients by the gastrointestinal route.

Establishment and characterization of a human gastric carcinoma cell line that is highly metastatic to lymph nodes.

The actual mechanisms by which carcinoma cells metastasize to lymph nodes are still unclear, and there is a need to establish in vivo experimental models suitable for the investigation of lymph node metastasis. For the purpose, we established a highly lymph node-metastasizing line, designated AZL5G, derived from a human gastric cancer cell line, AZ521, which had low capacity for lymph node metastasis. AZL5G cells transplanted orthotopically in the nude mouse stomach metastasize predominantly to the regional lymph nodes, showing little potential for hematogenous metastasis. AZL5G tumors developing in the stomach and regional lymph nodes showed poorly differentiated adenocarcinoma with medullary growth, and their histologic appearance strongly resembled that of parental AZ521. The growth activities in vitro of low-metastatic AZ521 and high-metastatic AZL5G were almost the same, but the tumorigenicity in vivo of AZL5G was significantly higher than that of AZ521. AZL5G cells also showed clearly higher abilities of cell locomotion and adhesion to type IV collagen and fibronectin in vitro as compared with AZ521 cells. Flow cytometric analysis demonstrated that the expression of integrin beta1 subfamily except for alpha6 integrin was generally increased in AZL5G cells than in AZ521 cells. Especially, the expression of alpha1 and alpha2 integrins in AZL5G cells was clearly higher than in AZ521, while alpha(v)beta3 integrin, E-cadherin, ICAM-1 and CD44H were not expressed by either cell line. The cell adhesion blocking assay showed that DGEA-containing peptide, which is composed of alpha2 integrin recognition sequence, significantly reduced the adhesiveness of AZL5G cells to type IV collagen as well as to type I collagen and laminin. Furthermore, the administration of anti-alpha2 integrin mAb or DGEA peptide in AZL5G-transplanted nude mice produced a significant reduction in the number of lymph node metastases. These data suggest that the up-regulation of alpha2 integrin expression by gastric cancer cells may play a critical role in the process of lymph node metastasis through the increased adhesiveness to type IV collagen. In conclusion, we established a gastric cancer cell line, AZL5G, with a highly metastatic potential to lymph nodes. This well-characterized line and its in vivo experimental model should be useful for investigation of the mechanisms of lymph node metastasis and for establishment of a new therapeutic approach for human gastric cancer.

Profiling analysis of differential gene expression between hematogenous and peritoneal metastatic sublines of human pancreatic cancer using a DNA chip.

We established the novel sublines HPC-1H5, HPC-3H4, HPC-4H4, and Panc-1H5, which have a high potential of liver metastasis, and HPC-1P5a, HPC-3P4a, HPC-4P4a, and Panc-1P5a, which have a high potential of peritoneal dissemination, derived from low metastatic HPC-1, HPC-3, HPC-4, and Panc-1cell lines, respectively. To clarify the molecular mechanisms of cancer metastasis and of the different levels of gene expression in a variety of metastatic potentials in pancreatic cancer, we performed a broad analysis of differential gene expression analysis between parental cell lines and metastatic sublines. In comparison with the parental cell lines, 65 and 36 genes were overexpressed and underexpressed in highly liver-metastatic sublines. On the other hand, 43 and 45 genes were overexpressed and underexpressed in highly peritoneal-metastatic sublines. uPAR and Serin protease were overexpressed, and E2A and IGF1R were underexpressed in both metastatic sublines. Hierarchical clustering analysis revealed 22 genes classifying liver, peritoneal metastatic sublines and low-metastatic parental cell lines. These genes might be targeted genes separating those two major metastatic forms after surgery. A greater number of cell line samples and more genes will have to be utilized in future studies in order to understand the involvement of genes in cancer metastasis more thoroughly. However, these results will help to clarify the molecular mechanisms of pancreatic cancer metastasis.

Differential gene expression screening between parental and highly metastatic pancreatic cancer variants using a DNA microarray.

To clarify the difference in genes expressed in hematogenous metastasis and peritoneal dissemination, a broad analysis of differential gene expression analysis between parental cell lines and established metastatic sublines was performed. Using an oligonucleotide array (Gene Chip, Affymetrix), approximately 2,000 genes involved in cancer were analyzed for each of the cell lines. HPC-4H4 (highly metastatic lines to the liver) compared with HPC-4 (low metastatic parental lines), in which 20 overexpressed genes and 5 underexpressed genes were recognized. HPC-4P4a (highly metastatic to the peritoneum) compared with HPC-4, in which 12 overexpressed genes and 15 underexpressed genes were also recognized. Analysis of HPC-4H4 and HPC-4P4a showed comparative up-regulation of 20 genes and down-regulation of 13 in the former, HPC-4H4. Further studies are needed to validate our hypothesis that some of the resulting differentially expressed genes might be implicated in the development of metastasis in pancreatic cancer. In conclusion, this genome-wide expression analysis will help to clarify the molecular mechanisms of cancer metastasis and of the different levels of gene expression in a variety of metastatic potentials in pancreatic cancer.

Metastatic-associated biological properties and differential gene expression profiles in established highly liver and peritoneal metastatic cell lines of human pancreatic cancer.

To elucidate metastasis mechanisms, we established a Panc-1H5 subline with a highly liver metastatic cell line and a Panc-1P4a with a highly peritoneal metastatic cell line, which were sequentially selected from the parental pancreatic cancer cell line Panc-1. Using these three cell lines, we investigated several biological properties and mRNA levels of differentially-expressed genes involved in cancer metastasis with a cDNA macroarray. The tumorigenicity, motile activity, adhesive activity and cytokine production of metastatic sublines were higher than those of parental Panc-1 cells. Particularly, in Panc-1H5 cells, adhesive activity to the extracellular matrix and angiogenetic factors increased, whereas in Panc-1P4a cells, motile activity was extremely enhanced compared with Panc-1 cells. Histopathological findings for the three cell lines were the same. In cDNA macroarray analysis of Panc-1H5 cells, 11 genes were up-regulated and 20 genes were down-regulated compared with parental Panc-1 cells. In Panc-1P4a cells, 7 genes were up-regulated and 13 genes were down-regulated compared with parental Panc-1 cells. This study provides a demonstration of global gene expression analysis of pancreatic cancer cells with liver and peritoneal metastasis and these results provide new insight into the study of human pancreatic cancer metastasis.

A case of partial autotransplantation of the liver in advanced hepatocellular carcinoma.

Hepatocellular carcinoma in Japan is frequently complicated by chronic hepatic disease such as chronic hepatitis and liver cirrhosis, and it is often impossible to decide the range to be resected only based on clinical stage and other tumor factors. We experienced a case with advanced hepatocellular carcinoma complicated by liver cirrhosis that directly infiltrated into the right and middle hepatic vein. Right trisegmentectomy was performed, the tumor site was extracorporeally removed and the hepatic posterior segment was autotransplanted. An anastomosis of the right hepatic vein and the inferior vena cava was performed with a vascular prosthesis. The patencies of the anastomosed vessels in the vascular reconstructions were confirmed by Doppler sonography, which was very useful, providing an easy and exact evaluation of hepatic blood flow at the patient's bedside. Throughout the post-operative course before the patient's discharge, no abnormal hepatic function was found. Though cases for which partial hepatic autotransplantation is appropriate may be few, this operation procedure, which applies hepatic transplantation techniques, is significant in that it increases the resectability and achieves curative resection of hepatocellular carcinoma.

Epstein-Barr virus-associated gastric cancer in a patient with dermatomyositis.

A 59-year-old man was admitted presenting systemic rash and muscle weakness. He was diagnosed to have dermatomyositis and a check was made for internal malignancy. Gastrointestinal endoscopy revealed a Borrmann type II tumor on the middle body of the stomach. Biopsy specimens showed a well differentiated adenocarcinoma, and total gastrectomy was performed. The final diagnosis was moderately differentiated adenocarcinoma invading into the proper muscular layer, with metastases to regional lymph nodes. Most of the neoplastic cells were shown to be positive for Epstein-Barr virus by means of EBV-encoded RNA in situ hybridization. The symptoms of dermatomyositis disappeared completely after surgery.

Surgical treatment for recurrent tumors of primary malignant melanoma of the esophagus: a case report and review of the literature.

The purpose of this communication is to present a case of resection performed for local recurrent tumors of primary malignant melanoma of the esophagus (PMME) and to review the relevant literature. The patient was a 54 year-old man who had received an intraabdominal esophagectomy with a total gastrectomy for primary malignant melanoma of the abdominal esophagus in another hospital, in November 1995. After the initial operation, he was treated as an outpatient. In August 1997, computed tomography and ultrasonography revealed recurrent tumors in the dorsal pancreatic lymph node and in the right adrenal gland. The recurrent tumor of the dorsal pancreas directly invaded the dorsal pancreas parenchyma and occluded the superior mesenteric vein and splenic vein, and the other metastatic tumor in the right adrenal gland existed in the absence of circumference invasion. Metastases of the PMME were confirmed in the dorsal pancreas, the superior mesenteric vein, splenic vein, and right adrenal gland, and were removed by a total pancreatectomy on October 7, 1997. By immunohistochemical staining, we found that the focal areas expressed S-100 protein and HMB-45 antibody. Currently (February 1998), the patient is alive and disease-free. PMME is an extremely rare tumor with a poor prognosis for survival. Only 2 cases of removal of recurrent tumors, including the present case, have been reported. The treatment of choice is surgical resection, even in cases of recurrence, because radiotherapy and/or chemotherapy have not been proven to be beneficial; however, they may play a palliative role if surgery is not possible.

[Study on the serum concentrations of gentamicin after intravenous drip infusion].

Serum concentrations of gentamicin (GM) were monitored after intravenous drip infusion of 60 mg over 30 minutes, 1 hour and 2 hours. These concentrations were compared with those after intramuscular injection. The mean peak serum concentration obtained at 30 minutes after intramuscular injection (5.09 micrograms/ml) and those obtained at the end of intravenous drip infusion (5.17--6.66 micrograms/ml) were comparable. Serum concentrations decreased to less than 2.0 micrograms/ml at 6 to 8 hours after injection or infusion in all cases except 1 with less body weight than others. Pharmacokinetic analysis showed that the T1/2 of GM ranged from 2.49 to 4.33 hours and that the AUC ranged from 19.66 to 27.09 hr X micrograms/ml. Results obtained in this study suggested that the usefulness of intravenous drip infusion over the time from 30 minutes to 2 hours is equal to that of intramuscular injection in the GM therapy.

[Bacteria isolated from intraabdominal infection and their susceptibilities to antimicrobial agents].

Bacteria isolated from intraabdominal infections during the period from July 1982 to June 1993 were investigated with regard to their classifications according to a joint research by 9 university hospitals in Japan. The following results were obtained. 1. A total of 971 strains were isolated from 684 out of 597 patients with peritonitis, and 287 strains out of 971 were isolated from postoperative peritonitis. 2. The most predominant organism isolated from patients with acute peritonitis was Escherichia coli (28%), followed by Bacteroides fragilis group (17%), Gram-positive anaerobic cocci (16%), Enterococcus spp. (9%) and Klebsiella spp. (8%). 3. Against E. coli, cefmenoxime, cefuzonam, cefozopran, aztreonam and carumonam showed MIC50 less than 0.05 micrograms/ml. Against B. fragilis group, erthromycin, clindamycin, imipenem, lincomycin and latamoxef showed MIC50 less than 0.78 micrograms/ml. 4. The most predominant organism isolated from patients with postoperative peritonitis was Enterococcus spp. (20%) and followed by Pseudomonas spp. (14%), and Staphylococcus spp. (13%), E. coli (9%), Enterobacter spp. (8%) and Klebsiella spp. (8%). We suggest that cefazolin, cefmetazole, flomoxef, cefmenoxime, cefuzonam, and latamoxef are the first choice agents in empiric therapy for the treatment of acute peritonitis.

[Year to year changes in isolation frequencies of different bacteria from postoperative infections].

Bacterial species isolated from postoperative infections during the period from July 1982 to June 1993 were studied regarding isolation frequencies of different species in different years in a joint research project involving nine (9) university hospitals in Japan. The obtained results are summarized as follows. (1) Altogether, 1,453 strains were isolated with 153 strains obtained during the most recent one year from July of 1992 through June of 1993. The most numerous source of isolation was postoperative intra-abdominal sepsis. (2) Gram-positive cocci were the most often isolated, among them methicillin-resistant Staphylococcus aureus was isolated in increasing frequencies until June, 1992. (3) In the last one year, Enterococcus spp. was isolated the most from postoperative infections followed by Staphylococcus spp. and Pseudomonas spp. Rates of isolation of anaerobic bacteria were relatively low with annual isolation frequencies ranging 8 to 15 per cent.