Serum immunoreactive anionic trypsin is diagnostic for rejection of vascularized pancreas allograft.
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Publications and source records attributed to W H Marks.
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Porcine Ileal Peptide (PIP) is located in the mucosa of the small bowel. We hypothesized that PIP may be useful as a marker for early intestinal ischemia or other acute processes of the mucosa. To test this hypothesis we developed a model of acute reversible intestinal ischemia in the pig. Following isolation of a 100-cm segment of ileum on a vascular pedicle baseline, serum and tissue samples were obtained. The vessels were then occluded for 60 min and the segment was reperfused. Serial serum samples were taken and analyzed for PIP and hexosaminidase (HEX). HEX enzyme activity in serum is known to be elevated in animals having intestinal necrosis. The Student t test for paired data was used. In preliminary studies we found that circulating HEX activity became elevated following 3 to 4 hr of vessel occlusion followed by reperfusion. In the current experiments, following 1 hr of ischemia, PIP rose significantly in the peripheral circulation, being 153.8 +/- 76.8, 909.0 +/- 150.4, and 898.3 +/- 128.1 ng/ml (P less than 0.001) at 0, 60, and 360 min after reperfusion of the segment. HEX on the other hand did not change significantly throughout the experiment, having been 766.0 +/- 28.1, 752.0 +/- 71.3, and 780.1 +/- 53.7 nM/liter (ns) at 0, 60, and 360 min following reperfusion of the segment. Histology demonstrated some clubbing, shortening and fracturing of villi with thinning of the tips of the villi in many cases. Immunospecific staining for PIP was present along the intact borders of the villi.(ABSTRACT TRUNCATED AT 250 WORDS)
Oral contraceptives have been implicated in the development of hepatic cellular adenomas (HCA) and associated in at least one report with focal nodular hyperplasia (FNH). Recurrence of lesions or progression while the patient is no longer receiving exogenous steroids is less well documented. Three cases are reported in which progression or recurrence of HCA after the discontinuance of steroids was documented. In addition, FNH and uterine leiomyomas with HCA were observed in all three cases. The mechanism of tumor formation secondary to the use of oral contraceptives remains undetermined. In two cases, liver tissues were tested for estrogen receptors; both were found to be negative. Although technique as well as the observed progression of these lesions or development of new lesions after the discontinuance of steroids may account for this negative finding, it suggests that induction of this process may be caused by means other than direct cellular stimulation by the exogenous hormones. Finally, these three cases call attention to a potential subgroup of patients having oral contraceptive-associated HCA who may have progression of their liver tumors when no longer receiving steroids and who require an aggressive treatment program and noninvasive follow-up examinations.
Duplex Doppler ultrasound (US) examination of the renal vasculature has proved valuable in assessing the kidney transplant. The normal renal allograft exhibits low-impedance arterial inflow similar to that seen in the normotopic kidney. The authors and others previously reported that a high vascular impedance, defined as either a pulsatility index (PI) greater than 1.8 or a resistive index greater than 0.9, indicates acute vascular rejection (AVR). Although AVR remains the most common cause of increased PI, the authors noted ten episodes among 180 serially followed-up transplants in which abnormal waveforms were clearly not due to rejection. Four other causes of increased vascular impedance are reported, including renal vein obstruction, severe acute tubular necrosis, pyelonephritis, and extrarenal compression of the graft. These new causes only slightly decrease the specificity of high vascular impedance for rejection. Furthermore, the cause can usually be recognized from the clinical history or other US findings.
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Transplantation of the pancreaticoduodenal allograft (PDA) has recently been advocated as a technique that is superior to the use of the segmental allograft. However, the effect of simple cold storage preservation on the PDA has not been studied. We investigated the effect of 24 and 4 hours of cold storage in Eurocollins solution on porcine PDA function after transplantation in pancreatectomized pigs. A regimen of cyclosporine and prednisone was used, which prevented rejection for at least 28 days after transplantation. Cold storage preservation for 24 hours uniformly resulted in PDA failure. Compared with recipients of immediately transplanted PDA, recipients of PDA cold stored for 4 hours had marked plasma hyperamylasemia (10,000 U/L versus 1932 U/L), relative glucose intolerance (K value -2.15 versus -2.66), hypoinsulinemia (peak immunoreactive insulin 11.0 microU/ml versus 34.7 microU/ml), and an abnormal pattern of insulin secretion as demonstrated with intravenous glucose tolerance testing. There was also a higher incidence of technical complications in the group transplanted with cold-stored PDAs. Our results suggest that there is a detrimental effect on porcine PDA function after only 4 hours of cold storage in Eurocollins solution.
Endoscopic procedures usually are not performed in the Emergency Department. However, on some occasions, it is essential that trained emergency physicians be able to perform endoscopic examinations. All physicians working in the Emergency Department should have an understanding of the role of endoscopy in the evaluation and treatment of gastrointestinal disorders, since in some cases, for example, those of massive upper and lower gastrointestinal hemorrhage, foreign body extraction, or functional and obstructive disorders of the colon, endoscopic procedures may be required on an emergency basis.
Immunoreactive anionic and cationic trypsins (irAT and irCT) were measured in blood samples taken daily from 20 pigs during 60 days after whole organ pancreatic transplantation. Immunosuppression was discontinued on the twenty-eighth day after transplantation. IrAT concentrations showed three distinct peaks, the first immediately after operation, the second around the seventh day after operation, and the third irAT peak was seen 2 to 9 days after discontinuation of immunosuppression therapy. IrCT levels paralleled the irAT levels only in the first peak immediately after transplantation. After this there was a dissociation between the concentrations of the two immunoreactive trypsins, with low irCT levels and high irAT levels. Increased irAT levels heralded rejection of the pancreatic allograft by 4 to 30 days (median 20 days) in 13 of the 16 rejecting animals (80%). In addition, low irCT levels preceded hyperglycemia in 13 of the 16 rejecting pigs by 2 to 47 days (median 21 days). The first postoperative peak of immunoreactive trypsins is thought to be related to the operative and storage trauma, whereas the second and third peaks are thought to reflect a rejection process. The results suggest that immunoreactive trypsins can be used as markers for pancreatic allograft rejection.
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Clinical pancreas transplantation (txp) using a pancreaticoduodenal allograft (pda) and the donor spleen has been applied as treatment for insulin-dependent diabetes mellitus. Inclusion of the spleen in the pda is purported to protect against thrombosis and may be of possible immunological benefit. In pancreatectomized pigs, we compared the results of pda txp with (n = 8) and without (n = 10) the donor spleen. Animals were maintained on cyclosporine (6 mg/kg/day i.v.) and prednisolone (1.5 mg/kg/day i.v. tapered over 7 days to a maintenance dose of 0.5 mg/kg/day i.v.). Pancreatic exocrine enzyme replacement was administered daily. In 10 recipients of the technically successful pda without the spleen, rejection (blood glucose greater than 150 mg/dl) was not seen in the 28 days after txp. Mean daily blood glucose was 95 +/- 8 mg/dl during this period. In contrast, 5 of 8 recipients of the technically successful pda with the donor spleen rejected their grafts an average of 13 days (range 7-16) after txp (P less than 0.01). Mean daily blood glucose was 88 +/- 21 mg/dl prior to the declaration of rejection and increased to 275 +/- 59 mg/dl after rejection (P less than 0.0001). Rejection was histologically confirmed in all cases. None of the recipients of the pda with the donor spleen developed signs of graft-versus-host disease. Glucose tolerance testing carried out 28 days after transplantation in normoglycemic pigs from both experimental groups demonstrated no difference between the groups. In the porcine pda model used in this study, the inclusion of the spleen in the pda was associated with rejection of the transplant.
A case of a 4-year old child with a hepatic artery aneurysm after the mucocutaneous lymph node syndrome is reported. The child had obstructive jaundice and preoperative evaluation did not lead to the correct diagnosis. The aneurysm was resected and the postoperative course was unremarkable. The literature on this entity is reviewed.
The endoscopic collection of human pancreatic juice for chemical analysis is facilitated by the use of radiocontrast media. However, the effects of this material on pancreatic juice and the techniques used to analyze its proteins are unknown. This study has demonstrated no detrimental effects of a commonly used contrast medium on the pancreatic juice itself or on the analytic technique of radioimmunoassay and radial immunodiffusion. Likewise, the Phadebas enzymatic technique for amylase was not affected by this material. We conclude that techniques for the collection of pure pancreatic juice using radiocontrast material do not interfere with the analysis of pancreatic juice proteins using the techniques described.
High levels of immunoreactive pancreatic secretory trypsin inhibitor (PSTI) were demonstrated in the serum and peritoneal exudates of patients suffering from acute pancreatitis. Trypsin-like immunoreactivity in these fluids was found in complex with alpha 1-antitrypsin and in complex with alpha 2-macroglobulin and also as a free peak correlating to free trypsin(ogen). No trypsin-PSTI complexes or PSTI were demonstrated in the macroglobulin fraction of the peritoneal exudates. Saturated and partially saturated trypsin-alpha 2-macroglobulin complexes were prepared in vitro. PSTI was able to partially inhibit the BzArgNan-cleaving activity of both types of complexes in a slow dose-dependent non-linear reaction. Equilibrium was reached in each case within 1 h, but total inhibition was not reached even with large amounts of PSTI. Partially saturated trypsin-alpha 2-macroglobulin complexes were inhibited more readily than saturated complexes. The results support the concept of PSTI acting as a strictly local inhibitor of trypsin in compartments lacking plasma protease inhibitors.
Immunoreactive trypsinogen and pancreatic secretory trypsin inhibitor (PSTI) were demonstrated in pancreas by means of an immunoperoxidase technique. They had the same distribution in acinar cells of 'normal' human exocrine pancreas tissues. Ductal adenocarcinoma tissue and pancreatic undifferentiated carcinoma contained neither antigen. Scattered 'normal'-looking cells in the border area between normal and neoplastic tissue of both types of tumor stained positively for trypsinogen and for PSTI.
This study has traced the behavior of rat anionic trypsin-like immunoreactivity and pancreatic secretory trypsin inhibitor (PSTI) immunoreactivity in the serum of rats undergoing bile-pancreatic duct infusions of buffered solutions with and without the addition of the bile salt taurocholate. Enzymatic analysis of alpha-amylase was also done. A mild pancreatic inflammation followed infusion of buffer alone, as determined by gross inspection of the pancreas and the behavior of serum levels of the above proteins. Animals infused with buffer and 4% taurocholate had major inflammatory changes, including gross hemorrhage into the gland, and marked elevations in serum levels of the three proteins studied. Graphic analysis of the serum levels revealed distinct sharp rises in the serum levels of all three proteins in the taurocholate group. In the buffered saline group only an initial sharp rise was present, followed by a prolonged decrease back towards base-line values. The immunoreactive trypsin in the taurocholate group was present in three fractions with different molecular weights: trypsin in complex with protease inhibitors, trypsinogen, and trypsinogen, and degradation products. PSTI immunoreactivity showed the molecular size of free inhibitor and that of degradation products. The presence of trypsin in complex with protease inhibitors indicates the formation of active trypsin during acute pancreatitis, which is further supported by the presence of degradation products of trypsin and PSTI.
Small bowel carcinoid tumors usually metastasize to regional lymph nodes and the liver but metastases to the neck are extremely rare. Over a ten-year period 48 cases of small bowel carcinoid were diagnosed at our institution and of these, three cases (6%) were associated with neck metastases--one to the thyroid gland and two to cervical lymph nodes. The former patient and one of the latter patients had symptoms of the carcinoid syndrome. The other patient was asymptomatic and presented with a solitary neck mass. Urine levels of 5-hydroxyindolacetic acid (5-HIAA) were elevated in the two symptomatic patients but were undetectable in the asymptomatic patient. Extirpation of the involved cervical nodes and the primary small bowel lesion was performed in two patients. In addition, both patients have received chemotherapy with 5-fluorouracil. One patient remains asymptomatic four years after diagnosis but the other patient continues to have five to six bowel movements per day nine months after operation. Small bowel resection was performed in the patient with a metastasis to the thyroid. This patient died of sepsis after a second operation for an intraabdominal abscess. The histological patterns of the primary tumor and the metastatic lesions were similar and the cells of the metastases contained argentaffin-positive granules. We conclude that 1) an intraabdominal carcinoid tumor should be considered as the location of the primary tumor in patients who present with a neck mass containing metastatic carcinoid and 2) the prognosis for patients with extraabdominal metastases is similar to that for patients with intraabdominal disease only.
The incidence of nonobstructive colonic dilatation (NCD) is unknown, but the attendant mortality associated with perforation is nearly 50%. Patients with chronic renal failure and transplant recipients may manifest many of the conditions that have been implicated in the development of NCD. Mechanical obstruction and ischemic bowel disease must be eliminated as causes for colon dilatation. Over a four-year period eight patients (mean age 50 years) were treated for presumed NCD. Six patients with a mean cecal diameter of 12.8 cm were treated initially with colonoscopy. Five patients (83%) had successful endoscopic decompression; of the three remaining patients, one underwent urgent ileocolectomy for cecal ischemia after unsuccessful endoscopic decompression, a second (cecal diameter 13 cm) had a tube cecostomy performed as an initial procedure, and the third (cecal diameter 9 cm) was managed successfully with enemas and nasogastric suction. Two deaths occurred in the series (25%), but both were unrelated to colon distension. No complications of colonoscopy were observed. The sequelae of massive NCD (cecal ischemia, perforation, and protracted sepsis) are poorly tolerated in the immunocompromised patient. Conservative management may be employed in patients with a cecal diameter of 9 cm, but urgent diagnostic and therapeutic colonoscopy is recommended for patients with a cecal diameter of 12 cm or greater. Operative tube cecostomy may be necessary if colonoscopic decompression is unsuccessful or cannot be performed.