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Mucosal lesions and healing of the common bile duct were analyzed after various chemical and surgical insults in the rat by means of histologic and scanning electron microscopic investigations. Autogenous bile duct replacement is rapidly associated within the first 72 postoperative hours with complete epithelial cell desquamation, and its precocious consequence is biliary sludge. These lesions also occurred when the bile flow was diverted; the extrinsic devascularization and denervation did not produce extensive epithelial cell loss. Heparin perfusion within the biliary tree or the induction by glycerol of epithelial cell loss before bile duct transplantation is suggested in order to avoid extensive biliary sludge after bile duct transplantation.

Polytetrafluoroethylene grafts were used as a microvascular prosthetic material in rats with a patency rate of 75 per cent. Immediate evaluation of the interface by scanning electron microscopy and histologic examination confirm the blood compatibility of the material, that is, limited platelet and erythrocytic activation or fibrin formation, or both. However, a longer evaluation period as great as three months fails to demonstrate the development of an endothelial lining which does not cross over the suture lines. Similarly, at this time, the immediate adjacent artery remains also devoid of typical endothelial structure. This result suggests that endothelial reconstitution, if present, even on normal substructures remains a delayed process.

The anticoagulant activity of seven intravascular radiocontrast molecules (RCM) was evaluated in different in vitro systems using citrated human plasma. Each RCM was tested in a concentration range of 5 to 50 mM. The thrombin time and the reptilase time showed a dose-dependent lengthening of fibrinoformation, the recording of fibrinoformation exhibited a significant delay of fibrin monomer generation and polymerization although the amplitude of the fibrinoformation was not decreased. The interfering effect with fibrin clot formation impairs also global coagulation tests and monospecific coagulation tests using fibrinoformation as the final step of the assay, but a possible interaction between RCM and some specific coagulation factors cannot be excluded. RCM potentiated the anti-thrombin action of heparin but the inhibition or delay of fibrinoformation is not related to an antithrombinic effect of contrast media. The thrombin amidolytic activity is not modified by RCM but the generation of FpA is delayed and decreased. The ultrastructure of the fibrin clot is not altered at the end of the polymerization.

With the use of microsurgical procedures, sequential studies have been done to compare the short and long term outcome of the bile duct and the femoral vein as autogenous bioprostheses of the bile duct. Nonpretreated grafts of both types are associated with an early superficial cell loss, either epithelial or endothelial. An initial biliary sludge resulted with further consequences, that in biliary stasis, lithiasis and biliary cirrhosis. Both grafted ducts became epithelialized but were the site of an extensive inflammatory reaction followed by fibrosis within the underlying connective tissue and retraction of the graft. On the contrary, pretreatment of the grafts by immersion in concentrated glycerol allowed the initial cell shedding to occur before implantation. The process of epithelialization and glandular formation was not altered in these conditions, whereas the inflammatory and fibrotic reaction in the duct wall was reduced or absent.

The rat small bowel was perfused in vivo and ex vivo in the absence of biliary and pancreatic secretion. Intraluminal release of sucrase, alkaline phosphatase, aminopeptidases and enterokinase was significantly increased after administration of pentagastrin, caerulein and glucagon at doses ranging between 1 pg and 10 microgram. This suggests that there is a direct hormonal stimulation of the intestinal mucosa. This effect might at least partly be mediated through cyclic AMP since dibutyryl derivates of this cyclic nucleotide exerted a significant stimulatory effect on intraluminal release of proteins, sucrase and enterokinase, although the pattern of enzyme was quite different from the effect produced by the three peptides.

The nature and characteristics of the tissue that develops on the inner surfaces of vascular arterial PTFE prostheses have been investigated by histological, morphometrical, ultrastructural, and immunocytochemical criteria. The ability of this tissue to synthetize glycoproteins and glycosamino-glycuronoglycans (previously called mucopolysaccharides) has been compared to that of the normal arterial wall. PTFE prostheses were used for carotid replacement in the dog and studied until the 90th postoperative day. These prostheses were mainly characterized by (1) a limited or even absent neointimal tissue proliferation; (2) the absence of an endothelial-like structure on the prosthesis using scanning electron microscopy and immunocytochemical staining with rabbit antidog factor VIII-related antigen sera; (3) limited activities of both microsomial enzymes (sialyl transferase and N-acetyl-glucosaminyl-transferase) but marked xylosyl transferase activity; and (4) inverse qualitative distribution of the glycosaminoglycans, i.e., decrease of heparan sulfate and chondroitin-6-sulfate and increase of hyaluronic acid and dermatan sulfate. The absence of morphological evidence of an endothelial structure at the blood--prosthesis interface even 3 months after implantation and the marked functional impairment in the biosynthesis of macromolecular components responsible for the normal blood--vessel interface suggest that this newly developed tissue cannot be considered a true vascular endothelium.

The platelet function was investigated in 65 patients submitted to diagnostic excretion urography (injection of 60 ml contrast medium). Blood sampling was performed before (T0) 90 seconds after (T1) and 30 minutes after (T2) injection of the radiocontrast molecule (RCM). Five RCM of different osmolality ionicity and nature of the lateral chain have been tested. Platelet aggregation, platelet release of ATP, osmolality, total calcemia and ionized calcium level were determined on each plasma sample as well as RCM concentration at T1 and T2. Decrease (20 - 40%) of platelet aggregation occurred at T1, whichever platelet aggregating agent (ADP, collagen, Ristocetin or thrombin) were used (significant after Iopamidol 300 and Na Meg Ioxaglate). Platelet release of ATP induced by collagen was also decreased or delayed. These changes were rapidly reversible and a tendency to improvement was observed at T2. Among the five RCM tested, one (Na Diatrizoate) might be a proaggregating agent. No changes of osmolality occurred in the plasma and no correlation could be established between RCM concentration and platelet inhibition. A pathogenic hypothesis is suggested by the significant fall of total and ionized calcium level after RCM injection.

The course of haemostasis defects was investigated in dimethylnitrosamine (DMNA) acute liver necrosis. Before 18 hr there was no evidence of disseminated intravascular coagulation (DIC) nor of abnormal fibrinolysis. At 12 hr the level of the vitamin-K-dependent factors (factors II, VII, IX and X) was reduced to 25-63% of control. Factors V and VIII:C levels decreased to about 10 and 20% by 12 hr. Factor V was the only molecule which decreased significantly by 6 hr. The rapid decrease of these proteins might be related to an early parenchymal functional impairment attested by early structural lesions observed in the endoplasmic reticulum and nucleus. The isolated decrease of factor V in the absence of any significant change in serum transaminase (SGOT and SGPT) levels is proposed, at least in the rat, as an early criterion of hepatic failure.

The fate of autologous pericardium when used to replace a tricuspid valve leaflet has been investigated in dogs. Changes have been studied by means of macroscopic, mechanical, histological, scanning electron microscopy, and in vitro culture techniques. In each of nine experiments the valve failed and death occurred within the first 15 post-operative days. Retraction, thickening of the cusp, fibrinous deposition and/or tissue rupture were associated with a decrease of resistance to traction tests, decrease of elasticity and increase of viscosity of the implanted tissue. The early behavior of autologous pericardium was characterized by precocious inflammatory reaction on the valve leaflets, focal disruption of the collagenous structure of the leaflets, absence of fibroblastic cell infiltration as confirmed by in vitro culture of implanted pericardium and the lack of endothelial-like cell surface at the 10th-15th postoperative day.

Total pancreatectomy without duodenectomy is described in the dog. The technique is based on the recognition of an anatomic cutting line between the two peritoneal layers overlying the duodenopancreas in the dog. This allows selective suppression of the pancreatic vascular supply and anatomic dissection between the pancreas and the duodenum. Complete pancreatectomy is indicated by hyperglycemia, absence of detectable serum insulin, abnormal glucose tolerance tests and short survival time due to metabolic conditions. No surgical complication was noted, and this reliable model is proposed for experimental pancreatic transplantation studies.

Use of the posterior surgical approach for the management of villous adenoma of the rectum below the peritoneal reflection has been evaluated in eleven patients. There has been no mortality and no recurrence. The Kraske approach was also suitable in four patients with noninvasive adenocarcinoma arising within villous adenomas, although there is no place for this procedure in the treatment of invasive carcinoma.

The effects of corticosteroid have been studied in rats submitted to oral administration of prednisone (5 mg. per kg. per day) during 8, 15, 30, and 90 days. The results were compared to those obtained after parenteral administration of hydrocortisone acetate (50 mg. per kg. per day intramuscularly). The morphometric changes of the villus-crypt axis and the brush border enzymic content of the mucosa (sucrase, enterokinase, alkaline phosphatase, and aminopeptidase) were the parameters investigated at the duodenal, jejunal, and ileal levels. Oral administration of prednisone resulted in a significant increase of the duodenal villous height at the 15th (+ 13 per cent, p less than 0.01), 30th (+ 33 per cent, p less than 0.001), and 90th day (+ 56 per cent, p less than 0.001), whereas in the jejunum a constant decrease of the villous height was noted. Parenteral hydrocortisone administration did not affect intestinal morphology. Effects of oral corticosteroids on the microvillous enzymic activities were related to both intestinal level and duration of corticoids administration: (1) in the duodenum increase of sucrase, alkaline phosphatase, and aminopeptidase during 30 days followed by normalization at the 90th day, (2) an initial increase of sucrase, alkaline phosphatase, and aminopeptidase limited to the first 8 days in the jejunum, and (3) a significant rise of alkaline phosphatase (greater than 100 per cent, p less than 0.001) and enterokinase (greater than 100 per cent, p less than 0.001) in the ileum at the 15th day of treatment. Parenteral corticosteroid administration was associated with a significant increase of both sucrase and enterokinase activities. The present study suggests that: (1) Corticosteroids exert a direct effect on the intestinal morphology varying with the intestinal level and duration of treatment. (2) No correlation could be established between anatomic and functional changes. (3) Oral corticosteroids exert an enhancing effect of the brush border enzymic activities, even in the adult mucosa and particularly at the ileal level where they stimulate significantly the enterokinase mucosal activity. (4) Parenteral corticosteroids exert a more specific effect limited to sucrase and enterokinase enhancement.