A versatile dual-channel carbon dioxide (CO2) insufflator for various CO2)applications. The prototype.

BACKGROUND: Carbon dioxide (CO2), with its rapid absorptive nature, has been proven superior to atmospheric air as an insufflating agent in various clinical settings. However, CO2 insufflation has not gained wide clinical acceptance, mainly because there has been no suitable feeding system. The authors therefore have developed a versatile "dual-channel" CO2 insufflator that facilitates wider use of CO2. The objectives of this study were to introduce the authors' prototype insufflator, to evaluate its safety and performance, and to validate CO2 application using the prototype. METHODS: The prototype insufflator provides one CO2 inlet connected to a regular CO2 gas cylinder and two CO2 outlets positioned on the front and back of the device, respectively. The CO2 gas fed from the cylinder is pressure-regulated and divided into two independent conduits inside the device. The front outlet feeds CO2 gas for pneumoperitoneum at an electronically controlled pressure and flow rate. The back channel supplies CO2 gas at a fixed flow rate, allowing manual control of insufflation for various purposes. The device was evaluated with canine models. RESULTS: The prototype was safe and performed well. The CO2 application (colonoscopy in this series) using the back channel was feasible while intact CO2 pneumoperitoneum was simultaneously maintained via the front channel. There were no device malfunctions. The serial abdominal x-rays indicated that intraluminal CO2 insufflation such as that used for CO2 colonoscopy caused less residual intestinal gas than conventional air insufflation. CONCLUSIONS: The dual-channel CO2 insufflator enabled two different modes of CO2 insufflation at the same time from a single CO2 cylinder. The authors are now improving the prototype to allow safer and wider usage of CO2 in the operating room.

Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn's disease.

BACKGROUND AND AIMS: A characteristic feature of Crohn's disease (CD) is mesenteric adipose tissue hypertrophy. Mesenteric adipocytes or specific proteins secreted by them may play a role in the pathogenesis of CD. We recently identified adiponectin as an adipocyte specific protein with anti-inflammatory properties. Here we report on expression of adiponectin in mesenteric adipose tissue of CD patients. METHODS AND RESULTS: Mesenteric adipose tissue specimens were obtained from patients with CD (n = 22), ulcerative colitis (UC) (n = 8) and, for controls, colon carcinoma patients (n = 28) who underwent intestinal resection. Adiponectin concentrations were determined by enzyme linked immunosorbent assay, and adiponectin mRNA levels were determined by real time quantitative reverse transcription-polymerase chain reaction. Tissue concentrations and release of adiponectin were significantly increased in hypertrophied mesenteric adipose tissue of CD patients compared with normal mesenteric adipose tissue of CD patients (p = 0.002, p = 0.040, respectively), UC patients (p = 0.002, p = 0.003), and controls (p<0.0001, p<0.0001). Adiponectin mRNA levels were significantly higher in hypertrophied mesenteric adipose tissue of CD patients than in paired normal mesenteric adipose tissue from the same subjects (p = 0.024). Adiponectin concentrations in hypertrophied mesenteric adipose tissue of CD patients with an internal fistula were significantly lower than those of CD patients without an internal fistula (p = 0.003). CONCLUSIONS: Our results suggest that adipocytes in hypertrophied mesenteric adipose tissue produce and secrete significant amounts of adiponectin, which could be involved in the regulation of intestinal inflammation associated with CD.

Advantages of laparoscope-assisted surgery for recurrent Crohn's disease.

BACKGROUND: Laparoscopic surgery has been applied to patients with primary Crohn's disease, and its beneficial outcomes have been already investigated. However, there is no systematic study of laparoscopic surgery for patients with recurrent diseases. METHODS: We performed reoperation for 43 patients with recurrent Crohn's disease, including 23 patients who underwent laparoscope-assisted surgery. RESULTS: For all the patients, laparoscope-assisted surgery could be performed safely, even if the patients had been treated previously by open surgery or had undergone multiple abdominal procedures. Conversion to open or hand-assisted laparoscopic surgery was necessary for 16 patients (69.6%) because of dense adhesions (11 cases) or bulky tumor (5 cases). Importantly, even if the procedure was converted, the skin incision was significantly shorter than with open surgery, and postoperative recovery was faster, especially for the patients who underwent conversion to hand-assisted laparoscopic surgery. CONCLUSIONS: Laparoscope-assisted surgery is feasible and advantageous in reoperation for patients with recurrent Crohn's disease.

A new method of laparoscopic cholecystectomy using three trocars combined with suture retraction of gallbladder.

BACKGROUND AND PURPOSE: Since the establishment of laparoscopic cholecystectomy (LC) for benign gallbladder lesions, the four-trocar method has been the standard procedure. However, the fourth trocar generally is used just for fundic retraction of the gallbladder. We have developed a three-trocar method for LC and performed it in 132 patients. PATIENTS AND METHODS: After the creation of the pneumoperitoneum, the first 10-mm trocar sheath was inserted in the subumbilicus for the endoscope, the second 5-mm trocar in the epigastric paramedian point for the working port, and the third 5-mm trocar in the subcostal area for grasping forceps. Monofilament nylon with a straight needle was inserted through the right 7th intercostal space in the anterior axillary line, and the seromuscular layer of the gallbladder fundus was punctured and retracted toward the anterior abdominal wall. After that, usual cholecystectomy was performed. RESULTS: Among the 132 patients who underwent the three-trocar method, 10 cases (8%) needed a fourth trocar. No patient was converted to open cholecystectomy. There were no significant differences in the operating time, the length of hospital stay after the operation, or the use of analgesics between the three-trocar and the four-trocar methods. No major complication was recognized. CONCLUSION: This method also has cosmetic advantages. Therefore, we believe this method might be recommended for LC.

Results of performing mesh plug repair for groin hernias.

The simplicity and good postoperative results of mesh plug repair for groin hernias have been reported in numerous articles. We have been performing this procedure in our department for more than 5 years, and the present study was conducted to reexamine its clinical outcome from our viewpoint. A total of 224 patients with a collective 244 groin hernias underwent mesh plug repair between March 1993 and August 1998. There were 155 (63.5%) indirect hernias, 79 (32.4%) direct hernias, 2 (0.8%) femoral hernias, and 8 (3.3%) compound hernias; 27 (11.1%) were recurrent hernias. Two plugs were inserted in all the compound hernias and in two of the direct hernias with a diffuse weak inguinal floor. The mean operating time was 32.2min. The complications that developed during this study were continuous pain in four patients, seroma in two, and hematoma in one. The rates of recurrence were 0% for indirect hernias and 12.7% for direct hernias. The patients in whom recurrence developed underwent mesh plug repair again and have had no further recurrence. Our experience showed mesh plug repair to be an excellent technique for indirect hernias or recurrent hernias after mesh repair, but it might be unsuitable for direct hernias with a diffuse bulging weakness in the floor of the inguinal canal.

Alteration of V beta usage and cytokine production of CD4+ TCR beta beta homodimer T cells by elimination of Bacteroides vulgatus prevents colitis in TCR alpha-chain-deficient mice.

A major pathogenic factor for the development of inflammatory bowel disease (IBD) is the breakdown of the intestinal homeostasis between the host immune system and the luminal microenvironment. To assess the potential influence of luminal Ags on the development of IBD, we fed TCR alpha(-/-) mice an elemental diet (ED). ED-fed TCR alpha(-/-) mice showed no pathologic features of IBD, and their aberrant mucosal B cell responses were suppressed. Similar numbers of CD4(+), TCR betabeta homodimer T cells (betabeta T cells) were developed in the colonic mucosa of ED-fed mice; however, Th2-type cytokine productions were lower than those seen in diseased regular diet (RD)-fed mice. The higher cytokine production in diseased RD-fed mice could be attributed to the high incidence of Bacteroides vulgatus (recovered in 80% of these mice), which can induce Th2-type responses of colonic CD4(+), betabeta T cells. In contrast, ED-fed TCR alpha(-/-) mice exhibited a diversification of Vbeta usage of betabetaT cell populations from the dominant Vbeta8 one associated with B. vulgatus in cecal flora to Vbeta6, Vbeta11, and Vbeta14. Rectal administration of disease-free ED-fed mice with B. vulgatus resulted in the development of Th2-type CD4(+), betabeta T cell-induced colitis. These findings suggest that the ED-induced alteration of intestinal microenvironments such as the enteric flora prevented the development of IBD in TCR alpha(-/-) mice via the immunologic quiescence of CD4(+), betabeta T cells.

An increased number of CD40-high monocytes in patients with Crohn's disease.

OBJECTIVE: CD40-CD40 ligand (CD40L) interaction is essential for the T-lymphocyte-dependent immune response. This interaction may be operational in the pathogenesis of inflammatory bowel diseases (IBD). The present study examined the expression of CD40 in peripheral blood mononuclear cells (PBMNCs) and tissue specimens, and CD40-stimulated interleukin (IL)-12 release from PBMNCs in IBD. METHODS: The expression of CD40 in PBMNCs and tissue inflammatory cells was examined by flowcytometry and immunohistochemistry, respectively. IL-12 release was measured in cultured media of PBMNCs by an enzyme-linked immunosorbent assay. RESULTS: Most peripheral blood B-lymphocytes expressed CD40 in all subjects. However, in ulcerative colitis (UC) patients, a significantly increased mean fluorescence intensity (MFI) of CD40 on B-lymphocytes was detected, compared with control subjects and patients with Crohn's disease (CD). In contrast, both the percentage positivity and MFI of CD40 on monocytes of active CD subjects were significantly increased, compared with the other groups. In active CD patients, a high level of IL-12 release from PBMNCs was observed by CD40 stimulation, compared with those of the other groups. When primed with IFN-gamma, PBMNCs from inactive CD patients released a significantly high level of IL-12, probably via stimulation by the CD40 monoclonal antibody. In the affected mucosa of CD, numerous CD40-positive cells were demonstrated, and they were also CD68-positive, suggesting these double CD40/ CD68-positive cells are tissue macrophages. CONCLUSIONS: These results suggest that the examination of CD40 expression in PBMNCs might enable the differentiation of CD from UC. CD40-high monocytes in CD patients may play a role in the pathogenesis of CD.

Laparoscopic-assisted surgery for Crohn's disease: reduced surgical stress following ileocolectomy.

Recent progress in laparoscopic techniques has enabled operations for various intestinal disorders to be performed under laparoscopic assistance. This study was conducted to assess the benefits of performing laparoscopic-assisted surgery (LAS) in patients with Crohn's disease. LAS was performed in 24 selected patients with Crohn's disease, most of whom underwent ileocolic resection for ileitis and/or colitis with stenosis. To determine the benefits of LAS, the postoperative inflammatory parameters of these patients were examined and compared with those of 17 patients who underwent conventional open surgery. Despite giving all patients total parenteral nutrition (TPN) for more than 2 weeks preoperatively, two patients with large inflammatory masses involving enteroenteric fistulas required conversion to laparotomy. No laparoscopic procedure was converted for adhesions after previous resection or intraoperative complications. The maximum C-reactive protein values and body temperatures were significantly lower, and the time taken to normalize body temperature and leukocyte counts was significantly shorter in the LAS group than in the laparotomy group. LAS should be performed for patients with Crohn's disease in the inactive phase after appropriate nutritional support. Patients with terminal ileitis without a fistula are considered to have the highest indication for this procedure.

Insulin-like growth factor-1 modulation of intestinal epithelial cell restitution.

After superficial intestinal injury, the mucosal integrity is reestablished by rapid migration of epithelial cells from the adjacent area in a process called restitution. Our previous study suggested that growth hormone improves intestinal healing in an experimental small bowel ulceration, mediated by insulin-like growth factor-1 (IGF-1). The aim of the present study was to assess the role of IGF-1 in mucosal epithelial restitution using an in vitro epithelial wound model. Wounds were established in confluent monolayers of the intestinal cell line, IEC-6. Migration was quantitated in the presence or absence of IGF-1 as the number of cells migrating across the wound edge. Proliferation was assessed by thymidine incorporation. IGF-1-enhanced epithelial cell migration by 2- to 2.5-fold after 12- and 24-hour treatment, respectively, the first step involved in gastrointestinal wound healing. Cell proliferation was significantly stimulated by IGF-1 as well. In addition, expression of transforming growth factor-beta (TGF-beta) mRNA was significantly enhanced in the wounded monolayers treated with IGF-1. IGF-1 receptor mRNA was found to be detectable throughout the gastrointestinal mucosa and in the intestinal epithelial cells. In conclusion, these findings suggest that IGF-1 plays an important role in reconstitution of intestinal epithelial integrity after mucosal injury.

The importance of total parenteral nutrition-associated tissue zinc distribution in wound healing.

It is well known that zinc (Zn), an essential trace element, plays a role in wound healing. Although the importance of Zn supplementation in total parenteral nutrition (TPN) has been recognized, the difference in tissue Zn distribution induced by TPN and whether this difference influences local wound healing remains uncertain. Thus, we conducted a study using 30 Sprague-Dawley rats to investigate the influence of TPN-induced changes in tissue Zn distribution on wound healing at sites of intestinal anastomosis, muscle, and skin sutures. In the ordinary diet group, no significant differences were observed between subgroups with and without supplemental Zn in tissue Zn distribution or in the healing of intestinal, muscular, and cutaneous wounds. In the subgroup given a low-protein diet without supplemental Zn, a gross change in tissue Zn distribution was noted to occur with a concomitant marked decrease in Zn concentration and the tensile strength of wounded skin. These results indicate an association between wound healing and Zn concentration in the respective tissues in TPN-induced Zn deficiency with alternations in tissue Zn distribution. They also provide evidence of the local action of Zn in wound healing.

High Fas ligand expression on lymphocytes in lesions of ulcerative colitis.

BACKGROUND: The pathogenesis of ulcerative colitis is unclear, but cytotoxic T lymphocytes infiltrating the mucosa have been implicated in mucosal damage. The Fas ligand (FasL), expressed on cytotoxic T lymphocytes, induces apoptosis in cells expressing Fas. AIM: To analyse FasL expression in affected colonic mucosa to ascertain Fas-FasL interaction in ulcerative colitis. METHODS: FasL mRNA was quantified in colonic mucosal specimens from healthy subjects and patients with ulcerative colitis or Crohn's disease, using the competitive reverse transcription polymerase chain reaction. FasL mRNA localisation was determined by in situ hybridisation. Expression of Fas in colonic mucosa was analysed immunohistochemically. Phenotypes of lamina propria lymphocytes that expressed FasL were analysed by flow cytometry. RESULTS: FasL mRNA was strongly expressed in active ulcerative colitis lesions, but not in those associated with active Crohn's disease or active proctitis-type ulcerative colitis. In situ hybridisation showed that FasL mRNA expression occurred in mononuclear cells infiltrating lesions. Fas was expressed in epithelial cells in ulcerative colitis and Crohn's disease, and in normal subjects. Cytometry showed that FasL was expressed in CD3 lymphocytes infiltrating the lamina propria in active lesions. CONCLUSIONS: FasL is expressed in CD3 lymphocytes infiltrating into ulcerative colitis but not Crohn's disease lesions, suggesting that Fas-FasL induced apoptosis participates in the mucosal damage of ulcerative colitis.

Zinc deficiency enhances interleukin-1alpha-induced metallothionein-1 expression in rats.

This study investigated whether interleukin-1alpha-induced metallothionein gene expression is affected by zinc deficiency. Weaning male rats were fed a zinc-deficient (ZD) diet (2 mg zinc/kg) or a zinc-supplemented diet [50.8 mg zinc/kg; controls for the diet included pair-fed (PF) and ad libitum consumption groups (AL)] for 4 wk. All rats except those that served as controls for interleukin-1alpha administration, (injected with vehicle and killed at 0 h) were then injected subcutaneously with interleukin-1alpha (2 x 10(7) units/kg body wt) and killed at 3, 6, 12, 24 and 72 h after the injection. Compared with AL and/or PF rats, zinc depletion significantly reduced zinc concentrations in plasma and liver but not in kidney or intestine, and significantly reduced hepatic, renal, and intestinal metallothionein-1 mRNA levels analyzed by competitive reverse transcription-polymerase chain reaction (RT-PCR). Interleukin-1alpha injection reduced plasma zinc concentration and enhanced liver zinc concentration, but did not affect zinc levels in kidney or intestine. Metallothionein-1 mRNA was significantly elevated by interleukin-1alpha in liver, kidney and intestine of all groups; the levels in liver and kidney of ZD rats 6 h after the injection were significantly higher than those of AL or PF rats. Liver metallothionein protein levels were enhanced after interleukin-1alpha injection in both AL and ZD rats. Semiquantitative RT-PCR revealed significantly higher hepatic levels of interleukin-1 receptor type-I mRNA in ZD rats than in AL and PF rats but no differences in renal or intestinal tissues among groups before interleukin-1alpha challenge. In conclusion, zinc deficiency induces upregulation of metallothionein-1 gene expression in response to interleukin-1alpha challenge in rats.

Induction of nitric oxide synthase in rat intestine by interleukin-1alpha may explain diarrhea associated with zinc deficiency.

Synthesis of inducible nitric oxide synthase (iNOS) in the intestine may result in local tissue damage. We investigated whether a challenge with interleukin-1alpha could give rise to intestinal iNOS expression and diarrhea in rats of differing zinc status. Weaning male rats were fed a zinc-deficient (ZD) diet (2 mg zinc/kg) for 4 wk to induce zinc deficiency or a zinc-supplemented diet [50.8 mg zinc/kg; controls, including pair-fed (PF ) and ad libitum (AL) consumption groups], and then subcutaneously injected with interleukin-1alpha (2 x 10(7) units/kg body wt). Without the interleukin-1alpha challenge, ZD rats had significantly lower plasma zinc concentration than the other groups. Intestinal metallothionein-1 mRNA abundance was lower in ZD rats than in AL rats. iNOS was expressed in the intestine of ZD rats but not in the others. None of the rats experienced diarrhea during the feeding period. Interleukin-1alpha led to a reduction in plasma zinc concentration, enhancement in intestinal metallothionein-1 mRNA levels, and expression of the intestinal iNOS gene in all groups. However, the abundance of iNOS mRNA was significantly higher in ZD rats than in the other groups. The presence of iNOS protein was demonstrated by immunohistochemical staining in the intestine of ZD rats that had been treated with interleukin-1alpha 12 h earlier. In addition, diarrhea occurred in most of the ZD rats and some of the PF rats but not in AL rats after interleukin-1alpha treatment. We conclude that ZD rats respond to interleukin-1alpha challenge more severely than controls, reflected by a more marked and prolonged iNOS expression and a greater incidence of diarrhea.

Lock method using sodium hydroxide solution to clear occluded central venous access devices.

Occlusion of central venous access devices (CVADs) is not an uncommon problem duringlong-term parenteral nutrition. A number of techniques have been developed to deal with obstructed CVADs. This study investigated the effectiveness of the sodium hydroxide (NaOH) lock method for gradual CVAD occlusion. When a progressively declining flow was noticed, 0.1 N NaOH solution was injected into the CVAD and locked. Nineteen CVAD occlusions in 11 home parenteral nutrition patients were treated Sixteen of 19 trials cleared the occlusions, whereas 3 of 19 failed. One of the failures was due to a mechanical occlusion and the other two were able to be restored by using ethanol. There were no significant complications. The benefits of this method are: (1) a shorter treatment time and a lower dose than NaOH infusion therapy, (2) it does not require hospital admission and (3) it does not result in bursting of the catheter.

Laparoscopic cholecystectomy in patients with cardiac disease: hemodynamic advantage of the abdominal wall retraction method.

We examined the use of an abdominal wall retraction method instead of pneumoperitoneum in laparoscopic cholecystectomy for patients with cardiac disease to prevent the hemodynamic deterioration associated with pneumoperitoneum. Eight patients with cardiac diseases, mainly valvular or coronary artery diseases, underwent laparoscopic cholecystectomy under hemodynamic monitoring. Five patients without cardiac disease served as controls. As hemodynamic parameters, heart rate, mean systemic arterial pressure (mAP), mean pulmonary arterial pressure (mPAP), central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), and cardiac index (CI) were measured. The patients with cardiac disease showed significantly elevated mPAP and PCWP compared with the control group under pneumoperitoneum, and one patient showed critically decreased CI due to increased tricuspid regurgitation under pneumoperitoneum. These changes, however, were resolved on the abdominal wall retraction. There was no major perioperative complication. This abdominal wall retraction method is, therefore, favorable for patients with underlying cardiac disease to minimize the hemodynamic deterioration during laparoscopic cholecystectomy.

Laparoscopic intragastric surgery for gastric leiomyoma.

Laparoscopic intragastric surgery (LIGS) was performed on a 63-year-old man with a gastric leiomyoma adjacent to the cardia. Because the tumor was about 5 cm in maximum diameter and showed ulceration, the possibility that the tumor was a leiomyosarcoma could not be ruled out preoperatively. Conventionally, major surgery has been performed on patients with a tumor located near the cardia, although it was not always malignant. Enucleation by LIGS enabled us to avoid excessive invasiveness and provided a favorable result. LIGS may be an appropriate new, minimally-invasive operation for gastric myogenic tumors and should be considered for such cases.

Beneficial effects of growth hormone combined with parenteral nutrition in the management of inflammatory bowel disease: an experimental study.

BACKGROUND: Growth hormone (GH) improves net protein anabolism and stimulates wound healing. Although GH is also known to exert the trophic effect on the intestinal tract, its role in the healing of intestinal ulceration is not known. The aim of this study was to evaluate the effects of exogenous GH coinfused with parenteral nutrition (PN) in an experimental model of inflammatory bowel disease in rats. METHODS: All rats underwent central venous cannulation and were randomized to two groups after induction of small intestinal ulceration with indomethacin. Both groups received the same PN formula. In addition, the GH group (n = 10) received subcutaneous injections of human GH at a dose of 1.0 IU/kg daily for 4 days, whereas the control group (n = 10) received injections of normal saline solution. Nitrogen balance, macroscopic inflammation score, intestinal myeloperoxidase activity, DNA content, and mucosal permeability were determined for each rat. Insulin-like growth factor-I (IGF-I) mRNA was detected by reverse transcription and polymerase chain reaction. RESULTS: Administration of GH significantly improved the cumulative nitrogen balance, ameliorated the gross inflammation score, and decreased intestinal myeloperoxidase activity. Similarly, intestinal permeability was significantly decreased in the GH group as compared with the control group. GH treatment resulted in increased plasma concentration of IGF-I and IGF-I mRNA expressions in both the liver and the small intestine compared with those in the control group. CONCLUSIONS: Exogenous GH plays an important role in accelerating intestinal healing in an experimental model of small bowel ulceration in rats. The mechanisms may include the stimulated IGF-I production, which thereafter augments intestinal epithelial cell growth.

Total parenteral nutrition increases uptake of latex beads by Peyer's patches.

BACKGROUND: Dysfunction of the intestinal barrier, as evidenced by increased intestinal permeability and bacterial translocation, has been reported under total parenteral nutrition (TPN). However, the role of Peyer's patches on the intestinal barrier in TPN is not well understood. We investigated whether TPN alters the uptake of microparticles by the follicle-associated epithelium of Peyer's patches. METHODS: Twenty rats were divided into two groups, a control group and a TPN group. Fluorescent polystyrene latex beads, 3.2 +/- 0.2 microns in diameter, were used as a probe for measuring the uptake by Peyer's patches. After 1 week of consuming either the control or TPN diet, rats were killed. On the day of killing, 0.1 mL of latex beads solution was injected into a 1-cm length of ileal loop, within 10 cm of the ileocecal valve. Samples were taken after 30 minutes of injection, sectioned by cryostat, and then viewed under a fluorescent microscope. Follicle-associated epithelial length and particles were counted using a confocal laser scanning microscope. The number of particles within each compartment was standardized per unit length of epithelium of Peyer's patches. RESULTS: Particle numbers within Peyer's patch dome of the TPN group were significantly increased compared with those of the control group (p < .01). CONCLUSIONS: These data suggest that dysfunction of the intestinal barrier in TPN might be associated with a change of uptake by Peyer's patches.

Effects of endotoxin on intestinal hemodynamics, glutamine metabolism, and function.

The purpose of this study was to investigate the intestinal hemodynamics and gut glutamine metabolism during endotoxemia, and their correlation with altered intestinal absorptive capacity and permeability. Seventeen Sprague-Dawley rats were used in the study. The endotoxin group (ENDO) received endotoxin (10 mg/kg intraperitoneally, n = 9), while the control group (CONT, n = 8) received saline injection. Twelve hours later, D-xylose (0.5 g/kg) and fluorescein isothiocyanate-dextran (FITC-dextran, 750 mg/kg) were given by oral gavage. One hour later abdominal aortic (AA) blood flow, superior mesenteric venous (SMV) flow, mean arterial pressure (MAP), central venous pressure (CVP), and SMV pressure (SMVP) were also measured. The MAP, AA, and SMV blood flow decreased (P < 0.05), while the CVP and SMVP increased (P < 0.05) in the ENDO group as compared with the CONT group. The ENDO group showed significant decreases for both intestinal glutaminase activity and net intestinal glutamine uptake (P < 0.05). The D-xylose concentration in SMV decreased significantly (P < 0.05) in the ENDO group as compared with the CONT group. However, the plasma FITC-dextran concentration showed no significant difference between the groups. Endotoxin produced a hypodynamic effect in rats 12 h after intraperitoneal administration in association with both a decreased intestinal glutamine metabolism and an absorptive capacity.

Consecutive maintenance of human solitary and hereditary colorectal polyps in SCID mice.

Recently, the sequential changes from adenoma to adenocarcinoma have been well studied in human colorectal carcinogenesis. To study the precise clonal changes from colorectal polyps to cancer, we have established an experimental system to maintain human colorectal polyps in severe combined immunodeficient (SCID) mice that have been improved by the selective inbreeding of C.B17-scid/scid homozygous male and female showing undetectable serum IgG and IgM (< 1 microgram/ml). Two of two solitary polyps from two nonhereditary colon polyp patients, four of five colon polyps from two Peutz-Jeghers' syndrome patients and one polypoid lesion from a familial polyposis coli (FAP) patient grew very slowly but steadily, at approximately one-tenth the rate of their malignant form, (i.e., adenocarcinoma), in the improved SCID mice and were maintained for a long period (more than 2 years), over several mouse generations. However, two polyps from FAP and Peutz-Jeghers' syndrome patients could not be transplanted further because of microinfection at the transplanted site due to incomplete sterilization of original human tumors prior to surgical operation (endoscopic polypectomy). Transplanted colon polyps had a semitransparent, soft and sticky appearance, with cells containing large amounts of mucin. Malignant transformation of human colon polyp to adenocarcinoma has not been observed during the maintenance period (about 2 years) in SCID mice. In the consecutively maintained human colon polyps, however, K-ras mutations were detected at codon 12, while these mutations were not found in their original polyps in the patients.