Duodenal ganglioneuroma: a rare cause of upper GI hemorrhage.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
M P Callery
Publications and source records attributed to M P Callery.
Endotoxin tolerance alters phospholipase C-gamma 1 and phosphatidylinositol-3'-kinase expression in peritoneal macrophages.
Although the molecular signaling mechanisms underlying macrophage endotoxin (LPS) responsiveness are not fully understood, alterations in intracellular phosphatidylinositol (PI) metabolism appear to contribute. We evaluated the effects of endotoxin tolerance (ET) induction upon peritoneal macrophage (PM) expression of the principal PI enzymes phospholipase PLC-gamma 1 (PLC-gamma 1) and phosphatidylinositol 3'-kinase (PI-3-K). Rats received either 5 mg/kg LPS (ET) or phosphate-buffered saline (nontolerant, NT) which enabled 88% of ET and 25% of NT to survive a 25 mg/kg LPS dose 3 days later. PM were harvested by lavage on Day 3 from both ET and NT rats. Following overnight culture, 5 x 10(6) PM in serum-free media were stimulated with 5 ng/ml LPS for 0 to 30 min. Cell lysates fractionated by SDS-PAGE were transferred to nitro-cellulose and blotted with PLC-gamma 1, PI-3'-K, and phosphotyrosine (4G10) monoclonal antibodies. Western immunoblots were developed by enhanced chemiluminescence and quantitated by densitometry. Unlike NT cells in which PLC-gamma 1 was expressed constitutively and increased with LPS stimulation, PLC-gamma 1 expression in ET cells stimulated with LPS was markedly reduced in three separate experiments. In contrast, ET cells expressed considerably higher concentrations of PI-3'-K to NT cells. Patterns of protein tyrosine phosphorylation were similar in both NT and ET cells regardless of LPS stimulation. The development of endotoxin tolerance decreased PLC-gamma 1 expression and markedly amplified PI-3'-K expression in macrophages. PI-3'-K-generated second messengers may contribute to unique signaling pathways responsible for tempered cellular responses to LPS.
Animals↗
Laparoscopic ultrasonography as compared with static or dynamic cholangiography at laparoscopic cholecystectomy. A prospective multicenter trial.
We compared laparoscopic ultrasonography (LICU) with static (S) or dynamic (D) cholangiography (IOC) for assessment of duct anatomy an calculi in 209 patients. LICU visualized ducts in 88% compared with 93% for IOC (P = 0.046). Nineteen patients (9%) had stones: 17 were found by LICU (89%) and 10 (53%) by IOC (P = 0.032). Time to perform LICU (7 +/- 3 min) was less than IOC (13 +/- 6 min) (P < 0.0001). Time to perform SIOC (12 +/- 5 min) and DIOC (14 +/- 6 min) did not differ (P = 0.48), nor did these tests differ in accuracy. LICU provided useful anatomical information but IOC better defined anatomic anomalies. LICU required less time but was less reliable at defining anatomy and complete duct visualization. LICU was more sensitive for stones. SIOC and DIOC did not differ objectively. LICU and IOC are complementary.
Bile Duct Diseases↗
Laparoscopic hepatobiliary surgery.
Laparoscopic hepatobiliary surgery has advanced rapidly in the past few years. Laparoscopic cholecystectomy has been the most significant advance and its value will become even greater as the incidence of biliary injuries is decreased. LCBDE and staging laparoscopy are very promising procedures. Other hepatobiliary laparoscopic operations such as liver resections and biliary-enteric anastomoses are still in developmental stages and will require a longer period of assessment.
Adult↗
Role of laparoscopic cholecystectomy in the management of acute gallstone pancreatitis.
Laparoscopic cholecystectomy has rapidly become the prime modality for removal of the gallbladder. However, as laparoscopic techniques for treating choledocholithiasis are evolving, we reviewed our experience with acute gallstone pancreatitis since the inception of laparoscopic cholecystectomy. Between November 1989 and March 1993, we treated 57 patients with acute gallstone pancreatitis. Cholecystectomy was performed during the initial admission in 46 patients (81%, group I), while 11 (19%) underwent delayed cholecystectomy at a second admission 2 to 9 weeks later (group II). Within group I, eight patients (17%) were thought to have contraindications to laparoscopic cholecystectomy and underwent open cholecystectomy. In the remaining 38 patients of group I, laparoscopic cholecystectomy was completed successfully. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) was performed in 23 of these patients (61%) and endoscopic sphincterotomy was performed in 6 patients (26%). In four other patients, the intraoperative cholangiogram revealed common bile duct stones that were removed using laparoscopic techniques. The 11 patients in group II were all treated by laparoscopic cholecystectomy; of these patients, 3 underwent preoperative endoscopic stone removal and 1 had choledocholithiasis managed laparoscopically. Postoperative hospitalization averaged 4 +/- 1 days (mean +/- SEM), and there was no major morbidity or 30-day mortality. This is the first large series of acute gallstone pancreatitis in the era of laparoscopic cholecystectomy. Our experience suggests that laparoscopic cholecystectomy with or without ERCP should be the primary approach for treating acute gallstone pancreatitis in the 1990s.
Acute Disease↗
Laparoscopic duodenal diverticulectomy following hemorrhage.
A 53-year-old man on warfarin therapy for an aortic valve prosthesis suffered a massive upper gastrointestinal hemorrhage. Urgent endoscopy revealed active bleeding from the apex of a large duodenal diverticulum. Bleeding was successfully controlled with heater-probe applications, and the patient recovered uneventfully. Because of the patient's lifelong need for anticoagulation therapy, elective laparoscopic duodenal diverticulectomy was subsequently done using intraoperative endoscopic guidance. The patient returned to full activity and diet within 3 days and has remained stable during the postoperative interval. We describe here a new minimal access approach to a complicated duodenal diverticulum combining laparoscopic and endoscopic techniques.
Diverticulum↗
Physiology of the pneumoperitoneum.
This chapter reviews the physiology of the pneumoperitoneum, focusing specifically on the traditional CO2 method and new alternatives which may ultimately replace it. A continued emphasis of providing for a safe, effective and physiologically benign intra-abdominal exposure will be mandatory if laparoscopic procedures of increased complexity and longer duration are to be applied to patients who are old or very young, and ill.
Acid-Base Equilibrium↗
Prostaglandin E2 downregulates Kupffer cell production of IL-1 and IL-6 during hepatic regeneration.
The mammalian liver possesses the ability to regenerate to its original size after a 70% partial hepatectomy (PHx). The capacity of rat Kupffer cells (KC) isolated at specific intervals after PHx to produce interleukin (IL)-1, IL-6, and prostaglandin E2 (PGE2) in response to endotoxin [lipopolysaccharide (LPS)] stimulation was evaluated in standard RPMI 1640 (1,200 microM L-arginine) and arginine-depleted RPMI 1640 (< 10 microM L-arginine) media. Because KC function in an environment in which high arginase activity results in negligible L-arginine levels, the 10 microM L-arginine RPMI 1640 was used to simulate the hepatic microenvironment. Regenerating liver KC 12-120 h after PHx responded to LPS with a significantly greater (P < 0.05) production of IL-1 and IL-6 in standard RPMI 1640. This enhancement of regenerating liver KC to produce IL-1 and IL-6 was increased (P < 0.05) by placing these same KC in 10 microM arginine RPMI 1640 culture media. During the same time period, regenerating liver KC produced significantly elevated (P < 0.01) PGE2, again with greater differences in the low-arginine media. In vivo KC PGE2 blockade by indomethacin (5 mg/kg) significantly (P < 0.05) inhibited hepatic regeneration. When the cyclooxygenase inhibitor indomethacin (10 microM) was added to cultures, the production of PGE2 by KC was prevented, and in arginine-depleted cultures, IL-1 and IL-6 production was upregulated (P < 0.05). We conclude that during hepatic regeneration, KC IL-1 and IL-6 production is elevated and is controlled in an autoregulatory fashion by elevated KC PGE2 production.
Animals↗
Endotoxin stimulates interleukin-6 production by human Kupffer cells.
Interleukin-6 (IL-6) induces acute-phase protein synthesis in human hepatocytes. We evaluated whether the contiguous hepatic macrophages, human Kupffer cells (HKC), produce IL-6 in response to an inflammatory stimulus. HKC were harvested from collagenase-digested normal liver biopsies and purified (greater than 95% by phagocytosis) by adherence. Following overnight culture, 5 x 10(5) HKC were repleted with fresh media with or without 2.5 micrograms/ml of endotoxin (LPS). Parallel cultures contained polymyxin-B (10 micrograms/ml) or antihuman-IL-6 antibody (4 units/ml). Timed supernatants were collected and IL-6 levels (ng/ml) measured (B9.9 proliferative bioassay). Data analysis was by the paired Student's t test. Unstimulated HKC produced negligible IL-6 levels (less than 0.150 ng/ml). Endotoxin invoked early and sustained HKC production of IL-6, which was completely (P less than 0.001) abrogated by the addition of the anti-IL-6 antibody. Polymyxin B, an LPS-inhibitor, also blocked (P less than 0.001) IL-6 production, indicating the specificity of the response to the inflammatory stimulus. This is the first evidence that HKC can produce IL-6 in response to LPS. Local intrahepatic production of IL-6 may provide a necessary paracrine signal for HKC to amplify directly neighboring hepatocyte acute-phase responses during inflammation in man.
Cells, Cultured↗
Organ interactions in sepsis. Host defense and the hepatic-pulmonary macrophage axis.
Endotoxin (lipopolysaccharide [LPS]) and tumor necrosis factor (TNF-alpha) have been implicated in the pathogenesis of sepsis-induced adult respiratory distress syndrome. To evaluate the possible interaction of the hepatic-pulmonary macrophage axis in the adult respiratory distress syndrome, we compared the kinetics of immunosuppressive prostaglandin E2, TNF-alpha, and interleukin 6 production in LPS-stimulated Kupffer cells and alveolar macrophages (AMs). Interleukin 6 production by Kupffer cells was significantly higher than for equal numbers of AMs. Kupffer cell TNF-alpha levels peaked early before decreasing as regulatory prostaglandin E2 levels rose. In contrast, AM TNF-alpha levels rose sharply and remained significantly higher than for Kupffer cells throughout culture coincident with negligible prostaglandin E2 production. Kupffer cell sequestration of LPS may normally invoke a coordinated cytokine response able to locally induce acute-phase hepatocytes. In hepatic failure, however, LPS spillover to the lung may promote adult respiratory distress syndrome by inducing unregulated AM TNF-alpha production within the pulmonary microenvironment.
Animals↗
Kupffer cell tumor necrosis factor-alpha production is suppressed during liver regeneration.
Mammalian liver regeneration following resection invokes intrinsic hepatic responses which result in rapid tissue repair. The role of soluble immune cytokines in this phenomenon is not known. The capacity of Kupffer cells (KC) from regenerating liver to produce the potent cytokine TNF-alpha was evaluated. Twenty-four hours after 70% partial hepatectomy (PHx) or sham operation, Kupffer cells were harvested from collagenase-digested Wistar-Furth rat livers and purified (greater than 95% by phagocytosis) by adherence. Following overnight culture with or without the cyclooxygenase inhibitor indomethacin (10 microM), 5 x 10(5) KC were repleted with fresh media with or without 2.5 micrograms/ml lipopolysaccharide (LPS). Supernatant TNF-alpha activities (units/ml) were measured using the L929 fibroblast lysis assay. With LPS, sham KC TNF-alpha levels were significantly higher (P less than 0.001) than those for PHx KC. Indomethacin significantly increased PHx KC TNF-alpha levels, but did not affect those for sham KC, suggesting autoregulation by arachidonic acid cyclooxygenase metabolites following PHx. We conclude that KC TNF-alpha production is suppressed following PHx by a mechanism apparently regulated by eicosanoid metabolism. During the stress of hepatic regeneration, a coordinated limitation of excessive TNF-alpha responses by PHx liver KC may naturally protect the host.
Animals↗
Intragraft delivery of 16, 16-dimethyl PGE2 induces donor-specific tolerance in rat cardiac allograft recipients.
The stable prostaglandin E2 analogue, 16,16-dimethyl PGE2 (di-M-PGE2) was continuously infused by osmotic pump directly into rat heterotopic cardiac allografts. Intragraft delivery of 20 micrograms/kg/day di-M-PGE2 for 2 weeks completely prevented graft rejection for more than 150 days (n = 10), while untreated Buffalo recipients rejected Lewis cardiac allografts within 8 days after transplantation (mean survival time = 7.4 +/- 0.5 days, n = 5). When given for only 1 week, 20 micrograms/kg/day had a partial effect, since 60% of recipients accepted grafts long-term and 40% experienced rejection by day 14 (n = 5). In contrast, systemic intravenous administration of 20 micrograms/kg/day di-M-PGE2 for 2 weeks could not prolong graft survival (MST = 7.0 +/- 0.0 days, n = 3), and the higher dose of 200 micrograms/kg/day resulted in death by day 2 (n = 5). Long-term BUF recipients of LEW cardiac allografts accepted LEW donor strain skin grafts for more than 35 days while rejecting third-party Wistar Furth skin grafts in a normal fashion (MST = 7.3 +/- 0.5 days, n = 3), indicating the induction of donor-specific tolerance. Long-surviving LEW cardiac allografts retransplanted into naive BUF recipients were rejected within 7 days (MST = 6.7 +/- 0.5 days, n = 3), indicating no change in graft immunogenicity. Therefore, a 14-day infusion of di-M-PGE2 directly into a strongly MHC-mismatched cardiac allograft uniformly has resulted in long-term engraftment and the development of recipient donor-specific tolerance.
16,16-Dimethylprostaglandin E2↗
Arginine-specific suppression of mixed lymphocyte culture reactivity by Kupffer cells--a basis of portal venous tolerance.
Portal venous administration of alloantigen abrogates the DTH response and prolongs heart and kidney allograft survival. Within the hepatic microenvironment, negligible L-arginine levels result from the effects of the highest tissue arginase activity of any organ (25 times greater than kidney). This study evaluated the effects of arginine availability on Kupffer cell immune function in the rat mixed lymphocyte culture. When 5 x 10(5) Wistar-Furth unfractionated lymph node cells (LNC) were cultured with 5 x 10(5) irradiated Lewis LNC in standard RPMI-1640 medium containing 1200 microM L-arginine, the proliferative response was not effected by the addition of 1 x 10(5) WF KC. However, when L-arginine-depleted medium (6 microM) was used, the MLC response was markedly reduced by the addition of KC. This was specific to arginine since media depletion of L-lysine, a similar basic amino acid, did not affect MLC/KC responses. When syngeneic WF KC were added as antigen-presenting cells to fractionated stimulator and responder T lymphocytes, WF/LEW MLC proliferation was restored in standard and L-lysine-depleted media, but did not increase in L-arginine-depleted RPMI 1640 medium. These responses correlated with a fivefold increase in KC prostaglandin-E2 (PGE2) production in the L-arginine-depleted medium. These findings support the hypothesis that diminished immune responsiveness in the low-arginine hepatic environment is effected, at least in part, by locally increased production of the immunosuppressant prostaglandin-E2.
Animals↗
A biologic basis for limited Kupffer cell reactivity to portal-derived endotoxin.
Despite continuous exposure to gut-derived endotoxin (lipopolysaccharide) under normal conditions, Kupffer cells (KC) fail to generate detrimental cytokine responses. KC function within a unique microenvironment in which high hepatic arginase activities (25 times greater than those activities in the kidney) result in negligible local L-arginine levels. To evaluate the relevance of this profound arginine deficiency on the physiologic function of KC, the kinetics of tumor necrosis factor (TNF-alpha) production and autoregulatory eicosanoid prostaglandin E2 (PGE2) production were compared in lipopolysaccharide-stimulated KC cultured with (1200 mumol/L) and without (10 mumol/L) L-arginine media. In (+)arginine culture the KC TNF-alpha production peaked early before decreasing as PGE2 production increased. In (-)arginine culture, however, KC TNF-alpha production was significantly (p less than 0.01) reduced, whereas PGE2 production was amplified (p less than 0.01). When cyclooxygenase blockade with indomethacin completely prevented KC production of PGE2 in (-)arginine culture, TNF-alpha production was upregulated (p less than 0.001 vs (-)arginine; p not significant vs (+)arginine). These arginine-specific depression of TNF-alpha responses appeared unique to KC because both TNF-alpha and PGE2 levels increased when peritoneal, pleural, and alveolar macrophages were stimulated by lipopolysaccharide in (-)arginine medium. This PGE2-dependent autoregulation of potentially harmful lipopolysaccharide-induced TNF-alpha responses may reflect an evolutionary adaptation by KC to their local hepatic environment and strategic anatomic position in the portal circuit, which optimally removes endotoxin and naturally protects the host.
Animals↗
Kupffer cell prostaglandin-E2 production is amplified during hepatic regeneration.
Prostaglandin-E2 increases in liver tissue after partial hepatectomy and stimulates DNA synthesis in primary cultures of hepatocytes. This study evaluated the capacity of Kupffer cells isolated at various intervals after partial hepatectomy to produce prostaglandin E2 in response to bacterial endotoxin. This stimulator of Kupffer cells is a normal endogenous component of portal venous blood. After partial hepatectomy (6 to 48 hr), when hepatic regeneration rates were greatest, regenerating liver Kupffer cells demonstrated a significantly greater capacity to produce prostaglandin E2 in response to bacterial endotoxin than did equal numbers of Kupffer cells from time-matched, sham-operated control animals. However, by 12 days after partial hepatectomy, when liver mass had been more than 83% restored, regenerating liver Kupffer cell prostaglandin E2 production had decreased to levels produced by sham KC. We postulate that high levels of Kupffer cell-derived prostaglandin E2 provide a critical paracrine signal fundamental to the initiation and control of growth by neighboring hepatocytes during liver regeneration.
Animals↗
Cyclooxygenase blockade abrogates the prolonged survival resulting from drainage of rat cardiac allografts into the portal vein.
Explore the source record for details and available documents.
Animals↗
Kupffer cell blockade increases mortality during intra-abdominal sepsis despite improving systemic immunity.
The effect of Kupffer cell (KC) blockade on systemic immunity during intra-abdominal sepsis was evaluated. Gadolinium chloride, a rare earth metal, reduced KC phagocytosis by 75% when it was given to BALB/c mice for 2 days. Thereafter, control mice and mice with KC blockade underwent either a sham operation or a cecal ligation and puncture. As indicators of systemic cell-mediated immunity, delayed-type hypersensitivity responses to soluble antigen and cellular alloantigen were measured 24 hours after the abdominal operations. The activation of KCs was assessed by their in vitro interleukin 1 production. Control septic mice were profoundly immunosuppressed and demonstrated marked KC activation. Septic mice with KC blockade, however, demonstrated less systemic immune hyporesponsiveness and significantly reduced KC activation, but died more rapidly. We concluded that despite apparent improvement in systemic immunity by KC blockade during intra-abdominal sepsis, the resulting impairment in functional phagocytic integrity predisposes to significantly higher mortality.
Abdomen↗
Kupffer cell blockade prevents induction of portal venous tolerance in rat cardiac allograft transplantation.
Pretransplant portal venous (pv) administration of donor antigen induces allospecific partial tolerance. Although the involved mechanism has not been defined, antigen presentation by Kupffer cells (KC) in the liver is considered to be critical. We evaluated the effect of KC blockade on this pv tolerance induction in Buffalo (RT1b) rats receiving Lewis (RT1(1] cardiac heterotopic allografts. Control rats received no treatment, while experimental animals received 25 X 10(6) ultraviolet B-irradiated (12,000 J/m2) donor spleen cells via either the iv (systemic intravenous) or the pv routes 7 days before transplantation. Gadolinium chloride (GdCl3), a rare earth metal known to inhibit KC phagocytosis, was given (7 mg/kg) 1 and 2 days before pv preimmunization. Cardiac graft prolongation was obtained by pv (MST = 13.3 +/- 1.9 days, n = 6, vs control = 7.3 +/- 0.5 days, n = 6; P less than 0.001) but not by iv preimmunization (7.7 +/- 0.7 days, n = 6, NS vs control). KC blockade abolished the pv tolerance, as indicated by abrogation of graft prolongation (PV + GdCl3 = 8.0 +/- 0.8 days, n = 6, NS vs control). These findings suggest that effective alloantigen uptake by KC in the liver is essential for the induction of pv tolerance in rat cardiac transplantation.
Animals↗