Teruo Maeda

Hepatic injury and lethal shock in galactosamine-sensitized mice induced by the superantigen staphylococcal enterotoxin B

BACKGROUND/AIMS Staphylococcal enterotoxin B (SEB) acts as a superantigen binding to class II major histocompatibility complex proteins, and this complex stimulates T cells. The aim of this study was to investigate the pathogenic effects of SEB on hepatic injury and lethal shock in mice. METHODS SEB was administered to D-galactosamine (GalN)-sensitized mice, and the degree of liver injury and levels of circulating cytokines were determined. In vitro cytokine production in response to SEB was also investigated. RESULTS Intraperitoneal administration of SEB (50 micrograms) caused lethal shock (50% mortality) associated with massive hepatic necrosis in GalN-sensitized mice, with no mortality on injection of up to 100 micrograms SEB alone. Within 2 hours after injection of SEB, serum tumor necrosis factor alpha (TNF-alpha) levels reached a peak, followed by high levels of serum interferon-gamma (IFN-gamma) up to 10 hours after injection. Passive immunization with anti-TNF-alpha/beta-neutralizing monoclonal antibody (mAb) protected GalN-sensitized mice from the lethal effects of SEB, with less protection with anti-IFN-gamma-neutralizing mAb. SEB induced the production of TNF-alpha and IFN-gamma in a dose-dependent manner from splenic mononuclear cells in vitro. CONCLUSIONS The results show that SEB contributes to lethal shock associated with severe hepatic injury in GalN-sensitized mice and suggest that TNF-alpha and IFN-gamma produced in response to SEB may be mediators of the lethal toxicity and hepatotoxicity of SEB.

Inhibition of Gastroesophageal Reflux by Semi-solid Nutrients in Patients With Percutaneous Endoscopic Gastrostomy

BACKGROUND Aspiration is one of the major complications after percutaneous endoscopic gastrostomy (PEG). The administration of semi-solid nutrients by means of gastrostomy tube has recently been reported to be effective in preventing aspiration pneumonia. The effects of semi-solid nutrients on gastroesophageal reflux, intragastric distribution, and gastric emptying were evaluated. METHODS Semi-solid nutrients were prepared by liquid nutrients mixed with agar at the concentration of 0.5%. The distribution of the administered radiolabeled liquid and semi-solid nutrients was monitored by a scintillation camera for 15 post-PEG patients. The percentage of esophageal reflux, the distribution of the proximal and distal stomach, and the gastric emptying time were evaluated. RESULTS The percentage of gastroesophageal reflux was significantly decreased in semi-solid nutrients (0.82 +/- 1.27%) compared with liquid nutrients (3.75 +/- 4.25%), whereas the gastric emptying time was not different. The distribution of semi-solid nutrients was not different from liquid nutrients in the early phase, whereas higher retention of liquid nutrients in the proximal stomach was observed in the late phase. CONCLUSIONS Gastroesophageal reflux was significantly inhibited by semi-solid nutrients. One of the mechanisms of the inhibition is considered to be an improvement in the transition from the proximal to distal stomach in semi-solid nutrients.

Natural killer cell may impair liver regeneration in fulminant hepatic failure

SummaryThe authors established a new experimental model of fulminant hepatic failure (FHF) with prolonged hepatocellular necrosis and impaired liver regeneration, and evaluated the immunological mechanisms related to the impaired liver regeneration in this model. A novel lipid A analogue, FS-112, was injected intravenously into male Balb/c mice, followed by a 70% partial hepatectomy 2 days later. Serum levels of T.Bil. and ALT rose 7 days after the partial hepatectomy, as compared with controls. In mice pretreated with FS-112, labeling indices of both BrdU and PCNA 36 hrs after the partial hepatectomy were significantly lower than those in the controls. Splenic lymphocytes harvested from the FHF mice 1–5 days after the partial hepatectomy showed a cytotoxic activity against regenerating hepatocytes with a peak effect on day 5. Cytotoxic activity against YAC-1 cells was also found up to 5 days after the partial hepatectomy, and resembled that directed against the regenerating hepatocytes. On the 5th day of FS-112 administration, there was a marked rise in the production of IFN-γ from splenocytes. When FK-506, an immunosuppressive agent, was given intracutaneously daily for 7 days, serum levels of T.Bil. and ALT significantly decreased, as compared with controls. Furthermore, the PCNA-labeling index 36 hrs after the partial hepatectomy was enhanced by the administration with FK-506 in the FHF mice. These results strongly suggest that the NK cells activated by IFN-y may be involved in killing the regenerating liver cells, and thus play a role in the pathogenesis of the impaired liver regeneration in FHF. Furthermore, it has been suggested that FK-506 may be beneficial for recovery from the impaired liver regeneration in FHF.

Predominant copper deficiency during prolonged enteral nutrition through a jejunostomy tube compared to that through a gastrostomy tube

BACKGROUND & AIMS Trace element deficiencies are known to occur during long-term enteral nutrition feeding. We compared the serum concentrations of trace elements between patients treated with gastrostomy and those treated with jejunostomy. METHODS Our subjects were 36 patients who underwent percutaneous endoscopic gastrostomy (PEG group) and 23 patients who underwent percutaneous endoscopic jejunostomy (PEJ group) and were maintained with enteral tube feeding for more than one year. The serum concentrations of copper, zinc, selenium, and iron were measured in the two groups. Clinical manifestations and the effectiveness of supplementation therapy against copper deficiency were also investigated. RESULTS From 6 months after the onset of enteral feeding, the copper concentration of the PEJ group was significantly decreased compared with that of the PEG group (p<0.001). There were no significant differences in the concentrations of zinc, selenium, or iron between the two groups. Severe copper deficiency was observed in 6 patients of the PEJ group and was accompanied with neutropenia and anemia. The copper deficiency was successfully treated in all of these patients by supplementation with 10-40 g of cocoa powder a day which was equivalent to a total daily dose of 1.36-2.56 mg of copper. CONCLUSIONS Prolonged PEJ tube nutrition tends to result in copper deficiency, and cocoa supplementation is effective for treating such copper deficiency.

Retrospective analyses of complications associated with transcutaneous replacement of percutaneous gastrostomy and jejunostomy feeding devices

BACKGROUND Feeding device replacement is often required for long-term maintenance after initial percutaneous endoscopic gastrostomy or jejunostomy placement. Although there are several case reports on serious complications of gastrostomy device replacement, there are few reports of an overall analysis of the complications associated with feeding device replacement. OBJECTIVE To evaluate the frequency and variety of complications of transcutaneous replacement of feeding devices. DESIGN A retrospective study. SETTING Single center: Nishimino Kosei Hospital. PATIENTS This study involved 363 consecutive patients undergoing a total of 1265 percutaneous gastrostomy or jejunostomy device replacements from March 2000 to September 2010. INTERVENTION A new replacement device was inserted through the ostomy tract by using an obturator after traction removal of the previous device. Endoscopic treatments were performed in the cases of fistula disruption or hemorrhage. MAIN OUTCOME MEASUREMENTS Complications and their outcomes. RESULTS Gastrostomy and jejunostomy devices were replaced 1126 and 139 times, respectively. There were 16 complications (1.3% of total replacements) consisting of 10 cases of fistula disruption caused by misplacement of replacement devices into the peritoneal cavity, 4 cases of hemorrhage, and 1 case each of colocutaneous fistula and device breakage. Anticoagulation or antiplatelet medications were continued in all 4 hemorrhage cases but in only 27 of 347 (7.7%) complication-free cases (P < .0001). There were no replacement-related adverse events that required surgical repair. LIMITATIONS A single center, retrospective analysis. CONCLUSION Fistula disruption and hemorrhage were the most common complications associated with device replacement. In patients on anticoagulants, caution is necessary to avoid hemorrhage after replacement. It is also important to verify that the replaced device is located in the GI tract lumen before feeding.

Clinical investigation of upper gastrointestinal hemorrhage after percutaneous endoscopic gastrostomy.

Background:  Upper gastrointestinal (GI) hemorrhage after percutaneous endoscopic gastrostomy (PEG) is sometimes reported as one of the serious complications. Our purpose was to clarify the cause of upper GI hemorrhage after PEG.

Treatment with a novel lipid A analogue, FS-112, and partial hepatectomy causes submassive liver necrosis and impaired liver regeneration in mice

A novel experimental model of submassive liver necrosis with impaired regeneration has been established. A novel lipid A analogue, FS‐112, was injected intravenously into male BALB/c mice, followed 2 days later by a 70% partial hepatectomy. Over the next 9 days, mice became severely jaundiced, with a peak total bilirubin (TBil) concentration of (mean±s.d.) 12.9±2.1 mg/dL 7 days postoperatively. In contrast, the TBil concentration in vehicle‐treated mice remained less than 2 mg/dL. Significant elevations of L‐alanine:2‐oxoglutarate aminotransferase (ALT) were also observed 3–7 days after the operation in mice pretreated with FS‐112, compared with mice pretreated with the vehicle. Submassive liver necrosis was observed with extensive mononuclear cell infiltration in mice treated with FS‐112 and subjected to partial hepatectomy. Furthermore, both the BrdU and the proliferating cell nuclear antigen (PCNA) labelling index (LI) 1 day following partial hepatectomy in mice pretreated with FS‐112 (8.6±4.3 and 7.9±4.2%, respectively) were significantly lower than levels in vehicletreated mice (25.8±3.8 and 26.5±10.5%, respectively). The time course of changes in the BrdU LI in liver specimens from mice treated with both FS‐112 and partial hepatectomy did not increase, even 3, 5, and 7 days postoperatively. Excellent liver regeneration with a PCNA LI 10‐fold higher than the resting level was observed in mice treated with D‐galactosamine hydrochloride. These results strongly suggest that this animal model of submassive liver necrosis may be suitable for clarifying the mechanisms of impaired liver cell regeneration often seen in fulminant hepatitis.

ENDOSCOPIC ULTRASONOGRAPHY-GUIDED GASTROSTOMY TUBE PLACEMENT FROM THE STOMACH

Dear Editor, A 92-year-old woman with severe dementia presented difficulty of oral intake after the treatments of a right femoral neck fracture and severe esophageal ulcer. Percutaneous endoscopic gastrostomy (PEG) was not available, because her stomach had largely ascended in the thoracic cavity. Subsequently, we attempted to place a gastrostomy tube (Ponsky PEG; Bard Access Systems, Inc., Salt Lake City, UT, USA) using the technique of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA), as shown in Fig. 1.The stomach was pushed downward to the abdominal wall from a subcostal location using an echoendoscope (GF-UCT240-AL5; Olympus Optical Co.,Tokyo, Japan) under fluoroscopic guidance. The interpositioning of the intestine, liver, spleen, and vessels was avoided using the echoendoscope, and we sought an appropriate puncture position using finger indentation from the abdominal wall (Fig. 2).A 19-gauge needle for FNA (Echo Tip Ultra; Cook Endoscopy, Winston-Salem, NC, USA) was used to puncture the abdominal wall, and the loop wire was inserted through the needle from the skin surface side. The needle was withdrawn into the endoscope and pulled out from the mouth with the endoscope. A 20-F gastrostomy tube was positioned by the pull-through technique. We compressed the gastric and abdominal walls between the internal and external bolster of the tube for 7 days until a gastrocutaneous fistula was successfully formed. Major reasons for failure of PEG include a lack of transillumination due to dislocation of the stomach, the anterior interposition of other organs, previous gastric resection, or the inability to carry out endoscopic insertion to the stomach. Chaves et al. reported five cases of EUS-guided PEG in patients lacking abdominal wall transillumination. Their method was to puncture a trocar from the abdominal wall over a 22-gauge needle inserted from EUS. In the present case, the use of a larger-bore puncture needle (19-gauge) Correspondence: Shinji Nishiwaki, Department of Internal Medicine, Nishimino Kosei Hospital, 986 Oshikoshi, Yoro-cho, Yoro-gun, Gifu 5031394, Japan. Email: wakky@nishimino.gfkosei.or.jp