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Biomedical subjects

S Post

Publications and source records attributed to S Post.

At least 19 recordsLinked to original sources
PubMed2000

Detrimental effects of octreotide on intestinal microcirculation.

BACKGROUND: Octreotide (OCT) is used for the protection of pancreato-intestinal anastomoses and for treatment of acute pancreatitis. Its effect on jejunal microcirculation after ischemia-reperfusion has not been investigated. MATERIAL AND METHODS: Intestinal ischemia was induced in Wistar rats (n = 8) by occlusion of the superior mesenteric artery for 40 min. Prior to reperfusion infusion of OCT (7.5 microgram/h) was started (n = 8). Microvascular perfusion of the jejunal mucosal and muscle layers was assessed and compared with that of groups without intervention (n = 16) by means of intravital microscopy. RESULTS: Ischemia-reperfusion decreased mucosal functional capillary density from 838.4 +/- 12.6 to 418.9 +/- 9.6 cm(-1). Mucosal capillary red blood cell velocity was reduced from 0.53 +/- 0.01 to 0.35 +/- 0.01 mm/s (P < 0.05). Permanent leukocyte adherence was increased. OCT without ischemia-reperfusion decreased functional capillary density (735.4 +/- 13.5 cm(-1)) and red blood cell velocity (0.46 +/- 0.01 mm/s). After reperfusion OCT led to perfusion heterogeneity demonstrated by villous stasis (26 +/- 4%) and a decrease in the index of mucosal perfusion (0.38 +/- 0.02). Functional capillary density was further decreased compared with ischemic controls (234.0 +/- 11.8 cm(-1)). Capillary red blood cell velocity was lower (0.30 +/- 0.01 mm/s) than in ischemic controls. CONCLUSIONS: OCT impairs microvascular perfusion of the jejunum both under physiological conditions and after ischemia-reperfusion.

Animals↗
PubMed2000

[Abandoned, effective and current aspects of surgical small bowel ileus therapy].

Because of the marked heterogeneity of patient groups and the diverse causes of obstruction, surgical therapy of the small-bowel ileus is difficult to standardize. A homogeneous strategy of intraoperative handling of the obstructed bowel (decompression, endoluminal splinting) as well as abdominal closure would be desirable. Adhesiolysis remains the most common procedure. Small bowel plication is still used by a minority of surgeons with the Noble's technique replaced by the Child-Phillips' technique and its modifications. However, as a result of the lack of controlled studies, there is no large body of evidence available to support the use of plication, long tubes or any other specific surgical intervention. This is an important task for the future, especially in view of incidence and economic importance of small bowel-ileus.

Humans↗
PubMed2000

Anti-ICAM-1 blockade reduces postsinusoidal WBC adherence following cold ischemia and reperfusion, but does not improve early graft function in rat liver transplantation.

BACKGROUND/AIM: The present in vivo study investigated the impact of a monoclonal antibody directed against the intercellular adhesion molecule-1 (ICAM-1) on initial microvascular reperfusion injury after liver transplantation. METHODS: Orthotopic, syngeneic liver transplantation including arterial reconstruction was performed in male Lewis rats after 24 h graft storage in University of Wisconsin (UW) solution at 4 degrees C. Animals received either an anti-ICAM-1 antibody (n=7), an IgG1 control antibody (n=8) or saline only (n=7). Hepatic microvascular alterations during the initial 90 min of reperfusion were assessed using intravital fluorescence microscopy. Early graft dysfunction was determined by analysis of bile flow. RESULTS: After treatment with anti-ICAM-1 mAb, hepatic microvascular perfusion was found improved when compared with that of IgG1- and saline-treated controls. In addition, anti-ICAM-1 mAb effectively reduced the number of permanently adherent white blood cells in postsinusoidal venules (284.4+/-59.1 mm(-2) vs IgG1: 371.9+/-26.7 mm(-2) and saline: 431.8+/-46.4 mm(-2); p<0.05). In contrast, the number of stagnant white blood cells in sinusoids was higher (p<0.05) in liver grafts with blocked ICAM-1 (320.6+/-17.2 mm(-2)) compared with that of IgG1- (215.2+/-11.1 mm(-2)) and saline-treated controls (226.4+/-14.0 mm(-2)). Measurement of hepatic uptake of fluorescent-labeled latex particles did not reveal significant differences in phagocytic activity. Finally, bile flow also did not differ between the three groups studied. CONCLUSION: Together these results indicate that ICAM-1 is involved in the process that mediates white blood cells adherence in postsinusoidal venules, whereas in hepatic sinusoids other mechanisms apart from ICAM-1-mediated white blood cells adherence seem to be fundamental for posttransplant white blood cells accumulation. Our data further suggest that white blood cells adherence in postsinusoidal venules via ICAM-1 does not make a major contribution to the pathogenesis of early cold ischemia/reperfusion injury after liver transplantation.

Animals↗
PubMed2000

Problems with intraoperative hyperthermic peritoneal chemotherapy for advanced gastric cancer.

BACKGROUND: Intraoperative hyperthermic peritoneal chemotherapy (IHPC) after total gastrectomy for advanced, serosa-penetrating gastric cancer has been demonstrated in several studies to reduce the incidence of peritoneal carcinosis and to prolong survival. METHODS: In a prospective pilot study, nine patients with advanced gastric cancer were selected to receive IHPC with Mitomycin and Cisplatin after total gastrectomy and systematic lymphadenectomy. RESULTS: All patients had nodal, and four patients distant, metastases. Six patients (66%) suffered from post-operative complications including renal failure, pancreatitis, pancreatic fistula and anastomotic dehiscence. Thirty-day mortality was zero. Six patients died within 3-10 months after surgery. Five of these deaths were related to peritoneal carcinosis and one patient died from cardiac failure 3 months after surgery. Three patients, respectively, have been alive for 12, 20 and 24 months at present, with suspected peritoneal tumour in the last patient. The 2-year probability of survival among our patients receiving IHPC is 29%. CONCLUSION: Intraoperative hyperthermic peritoneal chemotherapy carries a high risk of peri-operative complications and was not able to prevent or delay peritoneal tumour recurrence in patients with advanced gastric cancer.

Aged↗
PubMed2000

Impact of gastrin-releasing peptide on intestinal microcirculation after ischemia-reperfusion in rats.

We investigated the effect of gastrin-releasing peptide (GRP) and its antagonist RC-3095 on intestinal microcirculation after ischemia-reperfusion. Intestinal ischemia was induced in female Wistar rats by occlusion of the superior mesenteric artery for 40 min. Ten minutes prior to reperfusion, infusion of GRP or RC-3095 was started. A jejunal segment was exteriorized and the microhemodynamics of the mucosa and submucosa were examined by intravital microscopy and compared both with normal and ischemic controls (without application of the regulatory peptide). Ischemia-reperfusion significantly decreased functional capillary density from 891.2 +/- 14.1 to 398.3 +/- 11.4 cm(-1). Capillary red blood cell velocity was reduced from 0.46 +/- 0.01 to 0.37 +/- 0.01 mm/s (p < 0.05). Furthermore, both sticking and rolling of leukocytes were enhanced. 3.4 +/- 1.1% of the villi were not perfused at all. GRP infusion reversed the microcirculatory ischemia-reperfusion injury by increasing functional capillary density to 669.8 +/- 8.3 cm(-1) and red blood cell velocity to 0.62 +/- 0.01 mm/s (p < 0.05). In addition, application of GRP resulted in a complete absence of stasis (0%) in the villi. Leukocyte-endothelium adherence remained unchanged when compared to the ischemic controls. In contrast, application of RC-3095 caused an aggravation of microcirculatory disturbances demonstrated by a markedly increased number of non-perfused villi (42.5 +/- 4.2%; p < 0.05 vs. ischemic controls) and a significantly reduced functional capillary density (346.2 +/- 8.4 cm(-1), p < 0.05 vs. ischemic controls). In addition, RC-3095 led to an increased permanent leukocyte adherence in postcapillary venules whereas rolling was significantly reduced when compared to normal controls. We conclude that GRP in pharmacological doses has a protective effect on intestinal microcirculation during reperfusion. Furthermore, these data suggest that endogenous GRP may play a decisive role in the maintenance of microvascular integrity during reperfusion.

Analysis of Variance↗
PubMed1999

Inhibition of phospholipase A2-mediated arachidonic acid release by cyclic AMP defines a negative feedback loop for P2Y receptor activation in Madin-Darby canine kidney D1 cells.

In Madin-Darby canine kidney D1 cells extracellular nucleotides activate P2Y receptors that couple to several signal transduction pathways, including stimulation of multiple phospholipases and adenylyl cyclase. For one class of P2Y receptors, P2Y2 receptors, this stimulation of adenylyl cyclase and increase in cAMP occurs via the conversion of phospholipase A2 (PLA2)-generated arachidonic acid (AA) to prostaglandins (e.g. PGE2). These prostaglandins then stimulate adenylyl cyclase activity, presumably via activation of prostanoid receptors. In the current study we show that agents that increase cellular cAMP levels (including PGE2, forskolin, and the beta-adrenergic agonist isoproterenol) can inhibit P2Y receptor-promoted AA release. The protein kinase A (PKA) inhibitor H89 blocks this effect, suggesting that this feedback inhibition occurs via activation of PKA. Studies with PGE2 indicate that inhibition of AA release is attributable to inhibition of mitogen-activated protein kinase activity and in turn of P2Y receptor stimulated PLA2 activity. Although cAMP/PKA-mediated inhibition occurs for P2Y receptor-promoted AA release, we did not find such inhibition for epinephrine (alpha1-adrenergic) or bradykinin-mediated AA release. Taken together, these results indicate that negative feedback regulation via cAMP/PKA-mediated inhibition of mitogen-activated protein kinase occurs for some, but not all, classes of receptors that promote PLA2 activation and AA release. We speculate that receptor-selective feedback inhibition occurs because PLA2 activation by different receptors in Madin-Darby canine kidney D1 cells involves the utilization of different signaling components that are differentially sensitive to increases in cAMP or, alternatively, because of compartmentation of signaling components.

Animals↗
PubMed1999

Is delayed gastric emptying following pancreaticoduodenectomy related to pylorus preservation?

BACKGROUND: Delayed gastric emptying (DGE) is the most frequent postoperative complication after pylorus-preserving pancreaticoduodenectomy (PPPD). This prospective, non-randomized study was undertaken to determine whether the incidence of DGE may be reduced by modifying the original reconstructive anatomy with a retrocolic duodenojejunostomy towards an antecolic duodenojejunostomy. PATIENTS AND METHODS: The study was comprised of 51 patients who underwent PPPD between August 1994 and November 1997. The operation was carried out as originally described but was modified by performing the duodenojejunostomy antecolically. Clinical data were recorded prospectively, with special regard to DGE. RESULTS: After PPPD, the nasogastric tube could be removed at a median of 2 days (range 1-22 days) postoperatively; in two patients, the nasogastric tube was reinserted because of vomiting and nausea. A liquid diet was started at a median of 5 days (3-11 days); the patients were able to tolerate a full, regular diet at a median of 10 days (7-28 days). The overall incidence of DGE was 12% (n=6). No postoperative complications other than DGE were exhibited by 36 patients (71%). In this group, DGE was only seen in one patient (3%). In the second group, where postoperative complications other than DGE occurred (n=15), five patients (30%) exhibited DGE (P=0.002). CONCLUSIONS: DGE after PPPD seems to be of minor clinical importance following uncomplicated surgery. When taking the results into consideration, it can be said that, despite the lack of a control group, antecolic duodenojejunostomy might be the key to a low incidence of DGE after PPPD. In our experience, DGE is linked to the occurrence of other postoperative complications rather than to pylorus preservation.

Female↗
PubMed1999

HLA-DR expression in acute pancreatitis.

OBJECTIVE: To investigate the role of the monocyte/macrophage system in acute pancreatitis DESIGN: Prospective clinical study SETTING: University clinic, Germany SUBJECT: 37 consecutive patients who presented with acute pancreatitis. MAIN OUTCOME MEASURE: Correlation between function of monocytes measured by HLA-DR expression and outcome RESULTS: Patients were divided into three groups according to outcome: those with severe pancreatitis who died (n = 10), those with severe pancreatitis who survived (n = 15), and those with mild pancreatitis who survived (n = 12). There was a clear and significant difference between those with severe and those with mild disease. HLA-DR expression was initially depressed in both groups, but after the third day of treatment it started to recover significantly in those with mild disease (p < 0.05). The difference was also significant from day 7 onwards between those with severe disease who died and those with severe disease who survived (p < 0.05). CONCLUSION: Monocyte function as measured by HLA-DR expression (CD14+DR+) is reduced in patients with acute pancreatitis and does not recover in patients who are going to die (median < 20 relative antigen density units; RU).

Adult↗
PubMed1998

Complement inhibition by soluble complement receptor type 1 improves microcirculation after rat liver transplantation.

BACKGROUND: Recent observations provide evidence that complement is involved in the pathophysiology of ischemia/reperfusion injury. In this study, we assessed the impact of complement inhibition on hepatic microcirculation and graft function using a rat model of liver transplantation. METHODS: Arterialized orthotopic liver transplantation was performed in Lewis rats after cold preservation (University of Wisconsin solution, 4 degrees C, 24 h). Eight animals received the physiological complement regulator soluble complement receptor type 1 (sCR1) intravenously 1 min before reperfusion. Controls received Ringer's solution (n=8). Microvascular perfusion, leukocyte adhesion, and Kupffer cell phagocytic activity were studied 30-100 min after reperfusion by in vivo microscopy. RESULTS: Microvascular perfusion in hepatic sinusoids was improved in the sCR1 group (87+/-0.7% vs. 50+/-1%; P < 0.001). The number of adherent leukocytes was reduced in sinusoids (68.3+/-4.7 vs. 334.1+/-15.8 [adherent leukocytes per mm < or = liver surface]; P < 0.001) and in postsinusoidal venules after sCR1 treatment (306.6+/-21.8 vs. 931.6+/-55.9 [adherent leukocytes per mm < or = endothelial surface]; P < 0.001). Kupffer cell phagocytic activity was decreased in the sCR1 group compared to controls. Postischemic bile production reflecting hepatocellular function was increased by almost 200% (P = 0.004) after complement inhibition. Plasmatic liver enzyme activity was decreased significantly upon sCR1 treatment, indicating reduced parenchymal cell injury. CONCLUSIONS: Our results provide further evidence that the complement system plays a decisive role in hepatic ischemia/reperfusion injury. We conclude that complement inhibition by sCR1 represents an effective treatment to prevent reperfusion injury in liver transplantation.

Animals↗
PubMed1998

Increased expression of adenylylcyclase type VI proportionately increases beta-adrenergic receptor-stimulated production of cAMP in neonatal rat cardiac myocytes.

Cellular content of cAMP generated by activation of adenylylcyclase (AC; EC 4.6.1.1) is a key determinant of functional responsiveness in the heart and other tissues. We have tested two hypotheses regarding the relationship between AC content and beta-adrenergic receptor (betaAR)-mediated signal transduction in cardiac myocytes. First, that AC content limits adrenergic signal transduction, and, second, that increased AC, independent of (betaAR) number and G-protein content, yields a proportional increase in betaAR-mediated transmembrane signaling. We used recombinant adenovirus to increase AC isoform VI (ACVI) expression in neonatal cardiac myocytes. Cells that overexpressed ACVI responded to agonist stimulation with marked increases in cAMP production in proportion to protein expressed. In parallel experiments performed on cells transfected with lacZ (control) or ACVI, [3H]forskolin binding, used to assess AC protein expression, was amplified 6-fold, while betaAR-stimulated cAMP production from these cells was increased 7-fold. No changes in betaAR number, or in the heterotrimeric GTP-binding proteins, Galphas or Galphai2, were observed. Previous studies indicate that increased cardiac expression of betaAR or Galphas does not yield proportional increases in transmembrane adrenergic signaling. In contrast, the current data demonstrate that increased ACVI expression provides a proportional increase in beta-adrenergic signal transduction. Our results show that the amount of AC sets a limit on transmembrane beta-adrenergic signaling. We speculate that similar functional responses are possible in other cell types in which AC plays an important physiological role.

Adenylyl Cyclases↗
PubMed1998

[New data on recurrence rate of Crohn disease].

Despite numerous studies on the recurrence rate and risk factors following operations for Crohn's disease, unequivocal evidence on how to prevent recurrence non-medically and on the specific risks is lacking. Just two recommendations are supported by sufficient data: Do not perform radical resections with wide margins of safety and try to prevent the patient from smoking. Further studies are needed to delineate high risk subgroups for specific pharmacological interventions postoperatively.

Anastomosis, Surgical↗
PubMed1998

[Ambulatory co-disciplinary risk-adjusted preoperative care].

Routine preoperative studies in asymptomatic patients are not helpful for perioperative risk evaluation, and the cost is considerable. The decision regarding the status of a patient for elective surgery can be accurately predicted in 95% of cases on the basis of a complete history and physical examination alone; selective testing should be preferred. Interdisciplinary outpatient premedication is suitable for an individual risk evaluation, and a significant reduction in cost and inpatient treatment.

Adult↗
PubMed1997

Extrahepatic biliary obstruction impairs microvascular perfusion and increases leukocyte adhesion in rat liver.

To determine if disturbances of the liver microcirculation may be of pathophysiological relevance for liver damage during acute biliary obstruction, we studied the effects of bile duct ligation (BDL) on hepatic microhemodynamics and leukocyte adhesion in rat liver in vivo. Male Wistar rats were subjected to BDL for 3 days and 7 days, respectively. Sham-operated controls underwent laparotomy without BDL. After 3 days, intravital fluorescence microscopy (IVM) and hydrogen gas (H2) clearance were performed to study hepatic microvascular perfusion. Furthermore, leukocyte-endothelial cell interactions were assessed by IVM. Intercellular adhesion molecule 1 (ICAM-1) protein expression was studied by Western blot analysis and tissue immunofluorescence after 3 and 7 days, respectively. Analysis of microvascular perfusion by IVM revealed a marked impairment of sinusoidal perfusion after 3 days. Assessment of H2 clearance confirmed that overall hepatic microvascular perfusion was decreased. In addition, increased leukocyte adhesion in sinusoids and venules could be observed. A concomitant increase of ICAM-1 expression in liver tissue was also noted within the first week after BDL. Our results show that BDL is followed by a marked depression of the hepatic microcirculation and increased leukocyte adhesion in vivo within 3 to 7 days. Together, these findings suggest that deficits in microvascular perfusion and increased neutrophil infiltration may represent a potential source of liver injury during acute biliary obstruction.

Animals↗
PubMed1997

[Against the principle surgical indications in inguinal hernia].

It is generally accepted that most inguinal hernias should be operated electively. This study presents a risk calculation challenging this view. Three strategies are presented: prophylactic indication on principle (A), elective operation in every second case (B), and operation in case of strangulation only (C). On the basis of available epidemiological data it is calculated that, for the male German population aged 65 years and over 69,954 (A), 36,292 (B), and 2630 (C) inguinal hernia repairs would be necessary annually; 167 (A), 145 (B) and 123 (C) perioperative deaths would occur, connected with 1702 (A), 1373 (B) and 1048 (C) years of life lost, respectively. Thus, operation of every inguinal hernia would result in a (small) reduction of life expectancy. These data provide evidence that in elderly patients the indication for operative treatment of inguinal hernias should depend upon symptoms and suffering. There is no reason to operate on asymptomatic patients because of a presumed risk of strangulation.

Aged↗
PubMed1997

Inhibition of nitric oxide synthesis in ischemia/reperfusion of the rat liver is followed by impairment of hepatic microvascular blood flow.

BACKGROUND: Recent studies provide evidence that nitric oxide (NO) has beneficial effects in hepatic ischemia/reperfusion injury. The purpose of this study was to evaluate whether nitric oxide is involved in the regulation of hepatic microvascular perfusion after warm hepatic ischemia. Therefore, we performed a study using in vivo fluorescence microscopy. METHODS: Clamping of the left liver lobe was performed in male Wistar rats for the duration of 70 min. One experimental group (n=8) received L-NAME (Nw-nitro-L-arginine methyl ester hydrochloride), an NO-synthase inhibitor, 1 min prior to reperfusion. A second experimental group (n=8) received L-arginine (NO-substrate) continuously infused throughout the observation period. Controls (n=8) received equivalent volumes of an isotonic solution and underwent the same procedures. Hepatic microvascular blood flow and leukocyte-endothelial cell interaction was studied between 20 and 90 min after reperfusion using in vivo fluorescence microscopy. RESULTS: Inhibition of NO-synthesis during reperfusion by application of L-NAME caused a marked decrease in sinusoidal blood flow velocity. Furthermore, we noted an increase of non-perfused sinusoids in this group. Treatment with L-arginine improved functional perfusion of hepatic acini and reduced significantly the number of adherent leukocytes in sinusoids and venules compared to control animals. CONCLUSIONS: Our results provide further evidence that NO maintains postischemic hepatic microvascular perfusion and that inhibition of NO synthesis has detrimental effects on hepatic microhemodynamics during reperfusion.

Animals↗