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Biomedical subjects

S Post

Publications and source records attributed to S Post.

At least 19 recordsLinked to original sources

Assessment of hepatic phagocytic activity by in vivo microscopy after liver transplantation in the rat.

Phagocytic activity of sinusoidal lining cells was studied in 32 livers of male Lewis rats by in vivo fluorescence microscopy with epiillumination. Normal livers (group 1, n = 8) were compared with orthotopic syngeneic liver grafts 90 min after reperfusion after a period of cold storage in University of Wisconsin solution for 17 hr (group 2, n = 10) or 24 hr (group 3, n = 14). After bolus injection of fluorescence-labeled latex particles (3 x 10(8)/kg; diameter = 1.1 micron), zonal distribution and kinetics of adherence of latex beads were quantified by off-line video analysis. Hepatocellular function was estimated by the rate of bile production and biliary concentrations of bile acids. In normal livers 50%, 37% and 13% of injected latex beads adhered in zones 1, 2 and 3, respectively, whereas in transplanted livers a more homogeneous distribution was found (group 2: 37%, 41%, 22%; group 3: 37%, 39%, 24%; p less than 0.01 vs. controls by analysis of variance). Kinetic analysis of phagocytic activity showed no significant difference between group 1 (88% adherence of visible latex beads 3 min after injection) and group 2 (90% adherence). However, after long-term preservation in group 3, sinusoidal adherence was significantly faster (96.4% adherence; p less than 0.001). Bile secretion in group 2 was lower than in controls and severely depressed in group 3 (group 1: 1.1 +/- 0.07 microliter/min/gm liver [mean +/- S.E.M.]; group 2: 0.8 +/- 0.07; group 3: 0.1 +/- 0.04; p less than 0.001) without significant changes in bile acid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine

The impact of arterialization on hepatic microcirculation and leukocyte accumulation after liver transplantation in the rat.

This study investigated the influence of hepatic arterialization on early graft function, microcirculation, and leukocyte-endothelial interaction after syngeneic orthotopic liver transplantation in Lewis rats. Livers were preserved for 17 hr in UW solution and transplanted without rearterialization (group 1: n = 10) or with immediate arterial reconstruction (group 2: n = 10). Graft function was analyzed by bile flow; microcirculation was assessed by laser Doppler flowmetry (LDF) and intravital microscopy (IVM). In addition, flow behavior of leukocytes was quantified by IVM after i.v. injection of the WBC marker acridine orange. Improved graft function in group 2 was indicated by increased bile production during the observation period of 90 min after reperfusion (7.18 +/- 0.62 vs. 3.63 +/- 0.63 ml/100 g liver [mean +/- SEM] P < 0.001). In arterialized grafts LDF values increased by 22.9 +/- 3.8% upon reperfusion of the hepatic artery (P = 0.004). Arterialization increased WBC velocities in sinusoids (group 1: 0.29 +/- 0.02 mm/sec, group 2: 0.34 +/- 0.01 mm/sec, P < 0.001) and postsinusoidal venules (0.43 +/- 0.05 vs. 0.64 +/- 0.05 mm/sec, P = 0.029). In addition, the number of nonperfused midzonal sinusoids decreased significantly (8.5 +/- 2.2% of all sinusoids analyzed vs. 4.2 +/- 1.3%, P = 0.048). However, the marked sinusoidal and venular WBC adherence observed 1 hr after reperfusion was not altered by arterialization. It is concluded that arterial reconstruction in rat liver transplantation improves microvascular perfusion and graft function but this improvement does not relate to WBC accumulation within the graft. We propose that studies on hepatic preservation and postischemic reperfusion in the rat should be based on the physiological model of dual vascularization.

Animals

Soluble interleukin-2 receptor, interleukin-6 and interleukin-1 beta in patients with Crohn's disease and ulcerative colitis: preoperative levels and postoperative changes of serum concentrations.

Crohn's disease (CD) and ulcerative colitis (UC) show an intestinal activation of T cells and macrophages within the inflamed lesions. The aim of the present prospective study was to determine whether circulating interleukins (IL) represent useful markers of immune activation in vivo and to characterize their respective roles in monitoring disease activity. Serum concentrations of the soluble IL-2 receptor (sIL-2R), IL-6 and IL-1 beta were measured in 10 patients with CD and 10 patients with UC before, at day 10 and 2 years after resection of inflamed bowel segments. The data were correlated with neopterin, C-reactive protein and other standard parameters of disease activity. Preoperatively, mean sIL-2R concentration was 495 +/- 62 U/ml (mean +/- SEM; healthy controls; 210 +/- 25 U/ml; p less than 0.02) in CD and 705 +/- 120 U/ml (p less than 0.00002) in UC. The corresponding IL-6 serum concentrations were 37 +/- 6 U/ml in CD (controls: 11 +/- 0.6 U/ml; p less than 0.0036) and 33 +/- 6 U/ml (p less than 0.04) in UC. Two years postoperatively, sIL-2R was still elevated in 6 out of 9 patients in both disease groups. These patients did not differ from the remaining group with respect to disease activity. Serum IL-6, elevated in 7 patients with CD and in 6 patients with UC at day 10 postoperatively, had returned to normal in all patients by this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Effect of blood transfusions on rate of recurrence of Crohn disease].

The effect of perioperative blood transfusions on recurrence has been investigated in 261 patients with Crohn's disease who underwent a "curative" operation since 1981. Reoperations were necessary with a rate of approximately 3% per year. By Kaplan-Meier-analysis no difference could be detected between 120 patients with transfusion and 141 without (p = 0.407, log rank test). Statistical analysis of potentially interfering covariables revealed a significant effect of age and type of operation on postoperative recurrences. Even after stratification for these parameters it was impossible to confirm the protective influence of transfusions reported by others. However, in some subgroups there was a trend towards an association of blood transfusions with earlier reoperations.

Adult

Risks of intestinal anastomoses in Crohn's disease.

Six hundred fifty-eight intestinal anastomoses in 429 operations for Crohn's disease were studied prospectively during an 8-year period to detect variables connected with perioperative morbidity. Postoperative complications occurred in 9.7% of the patients, 4% had to be reoperated on, and the overall mortality rate was 0.5%. In multivariate analysis by stepwise logistic regression, the only variable significantly (p = 0.03) associated with overall rate of complications was long-term corticosteroid therapy. Serious complications were more common in cases of intra-abdominal abscesses (p = 0.01) and preoperative steroid medication (p = 0.03). The combination of both of these risk factors increased the rate of reoperations from 0.6% (no steroids, no abscess) to 16% (steroids and abscess). No significant association with postoperative complications could be found for age, sex, duration of disease, previous operations, nutritional status, emergency surgery, extent of disease, type, number, and localization of anastomoses, presence of proximal ileo-/colostomy, or histologically inflamed margins of resection.

Abscess

Rapid increase in the activity of enzymes of eicosanoid synthesis in hepatic and extrahepatic tissues after experimental liver transplantation.

Previous studies have demonstrated a marked release of prostanoids from hepatic tissue after liver grafting. In addition, eicosanoid synthesis was shown to be regulated at the level of key enzymes. The present study addressed changes of the local availability of these enzymes during and after porcine orthotopic liver transplantation. We determined kinetic parameters of cyclooxygenase (CO), the initial enzyme of prostaglandin synthesis, of prostacyclin and thromboxane synthase (PCS, TXS), two more peripheral enzymes, in microsomal preparations of hepatic and gluteal muscle biopsies, and the activity of 5-lipoxygenase (5-LO), the key enzyme of leukotriene synthesis. Maximal velocity (Vmax) of CO and PCS showed a 4-fold increase both in liver and gluteal muscle tissue 1 hr after reperfusion of the grafted liver and a more than 20-fold increase after 24 hr (P less than 0.001), whereas apparent affinities (Km) remained unchanged. In contrast, Vmax of TXS and the activity of 5-LO disclosed a striking increase only within the hepatic graft (P less than 0.001). No changes of enzymatic activity could be observed during donor operation, cold storage, and 5 min after reperfusion. Results were independent of the duration of preservation (3 hr and 20 hr with Euro-Collins) and the addition of Iloprost, a prostacyclin-analogue. These results suggest that after liver grafting, abnormalities at the level of local enzyme expression in hepatic and extrahepatic tissues might contribute to preservation damage and systemic injury of the host.

6-Ketoprostaglandin F1 alpha

[Enterostomy in Crohn disease].

Indications, technique and prognosis of 129 enterostomies in Crohn's disease are reported. Advanced perianal or entero-genital fistulas represented the predominant indication (60% of primary, 46% of repeated stomas). 85% of stomas were created in combination with intestinal resections. Preferred type of stoma was a loopileostomy (76% of primary stomas), whereas colostomies were avoided whenever possible because of increased complications. Patients initially presenting with rectal involvement or perianal fistulas were prone to need a stoma during the course of their disease while intraabdominal fistulas, abscesses, age, sex, and longstanding disease where of no prognostic significance. Up to now 50% of all temporary stomas and a third of those created for distal fistulas could be closed. The chance of closure increased significantly with duration of symptoms less than 7 years, not more than one previous operation or absence of rectal involvement.

Adult

Differential responsiveness to CD3-Ti vs. CD2-dependent activation of human intestinal T lymphocytes.

Human lamina propria lymphocytes were recovered from surgical specimens of unaffected large bowel and compared with peripheral blood lymphocytes (PBL) from the same individual. We investigated their capacities to respond to triggering stimuli delivered by mitogenic monoclonal antibodies directed at the T cell receptor/CD3 complex or, alternatively, the CD2 glycoprotein. In marked contrast to PBL, expression of the interleukin 2/interleukin 2 receptor system was markedly reduced in LPL following activation through the CD3/T cell receptor. Perhaps, more important, responses to CD2 triggering were similar or even stronger in LPL as opposed to PBL. This indicates that the CD2-dependent alternative pathway of T cell activation might serve a functional role in local immunity in the gut.

Antibodies, Monoclonal

Prostanoid release in experimental liver transplantation.

Prostanoids are biologically active mediators of inflammation and tissue injury. To investigate the role of prostanoids in orthotopic liver transplantation we used a porcine model and determined prostaglandin E2, 6-keto-prostaglandin F1 alpha, and thromboxane B2 in arterial, portal, and hepatic venous blood during organ harvesting, the recipient operation, and the early postoperative period. There were no significantly increased serum levels during the donor operation or at the end of cold storage. As early as 1 or 5 min after initiation of reperfusion of the transplanted organ, prostanoids in hepatovenous blood increased dramatically (100-500-fold). Changes in arterial and portal blood (10-50-fold) were less pronounced but still statistically significant. In surviving animals these values returned to normal within 24 hr. The hepatic release of metabolites of the arachidonic acid cascade after liver grafting indicates that the synthesis of prostanoids might contribute to morphological and functional alterations of the transplanted graft. In addition, the increased arterial values of circulating prostanoids may potentially participate in severe cardiovascular, hemostatic, and immunological alterations known to occur after liver transplantation.

6-Ketoprostaglandin F1 alpha