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Biomedical subjects

S R Munn

Publications and source records attributed to S R Munn.

52 records · Page 3Linked to original sources
PubMed1990

Histologic diagnosis of rejection by using cystoscopically directed needle biopsy specimens from dysfunctional pancreatoduodenal allografts with exocrine drainage into the bladder.

To determine the histologic features of rejection and to identify nonrejection causes of human pancreatic allograft dysfunction, we analyzed 31 needle biopsy specimens (17 pancreatic, 14 duodenal) obtained under cystoscopic direction from 15 dysfunctional pancreatoduodenal allografts with exocrine drainage into the bladder. Eight allografts undergoing rejection showed the most common histologic features of rejection to be diffuse mixed inflammatory infiltrates of pancreatic acinar tissue and duodenum wall. Diffuse infiltration of pancreatic acinar tissue by neutrophils was the earliest histologic change in rejection. Seven dysfunctional allografts not undergoing rejection ("nonrejection") showed a normal pancreas or various changes including acinar dilation with inspissation of secretions, fibrosis, cytomegalovirus inclusions, and enzymatic necrosis. The histologic changes in the duodenum paralleled those in the pancreas in both rejection and nonrejection allografts. We conclude that the histologic features of rejection in pancreatoduodenal allografts are distinctive. The changes seen in biopsy specimens accurately reflect the state of the graft and can be used to diagnose rejection and to identify other causes of graft dysfunction. Biopsy samples from the duodenum as well as the pancreas are diagnostically useful. The biopsy findings can be used to guide the clinical management of rejection and in the development of other noninvasive tests for rejection.

Biopsy, Needle↗
PubMed1989

Cold storage preservation of pancreatic tissue prior to and after islet preparation in a dog autotransplantation model.

Utilizing an intrasplenic canine islet autotransplant model, the effects of cold storage preservation on pancreatic tissue prior to and after collagenase dispersion were examined. A control series, in which freshly retrieved and prepared tissue was transplanted, yielded a 75% success rate (6/8). In contrast, when the pancreas was stored in modified silica gel filtered plasma (SGF I) for 24 hr, no autotransplant was successful (0/6). However, when the islet tissue was prepared following pancreatectomy and then stored in a mannitol-containing modification of SGF (SGF III), autotransplantation was successful in 83% (5/6) after 24 hr of preservation and in 60% (3/5) after 48 hr of preservation. Similarly, the islet tissue was stored in a hyperkalemic hydroxyethyl starch solution (HES) and this was successful in 20% (1/5) after 24 hr of preservation and in 50% (1/2) after 48 hr of preservation. Cold storage preservation techniques for the pancreas prior to islet isolation need to be refined, but dispersed islet-enriched pancreatic tissue can be successfully maintained at 4 degrees C for up to 48 hr prior to transplantation in dogs using established pancreas preservation solutions.

Animals↗
PubMed1989

Experimental pancreatic preservation prior to islet isolation and transplantation.

Preservation of the Lewis rat pancreas prior to islet isolation was accomplished by initial intraductal distension with the University of Wisconsin (UW) hydroxyethyl starch-lactobionate solution to which collagenase had been added, followed by simple cold storage at 4 degrees C for 0, 3, 12, 24, and 48 hr (n = 16-21 at each interval). The pancreases were then processed by digestion and mechanical dispersion to produce free islets of Langerhans. The mean islet yields (+/- standard errors of the means) were controls = 819 +/- 58 (n = 21), 3 hr = 867 +/- 51 (n = 20), 12 hr = 770 +/- 71 (n = 16), 24 hr = 805 +/- 62 (n = 18), and 48 hr = 722 +/- 55 (n = 16). None of these means differed significantly. The islets from pairs of donor pancreases (mean dose of islets = 1586 +/- 72) were transplanted intraportally into single isogeneic recipients with streptozotocin-induced diabetes (plasma glucose greater than 400). The preservation interval directly influenced the outcome of these islet isografts in the following manner: (i) Rates of functional success (nonfasting glucose less than 200 mg/dl) were 100% after storage times of 0 hr (n = 10), 3 hr (n = 8), and 12 hr (n = 8); 86% with a storage time of 24 hr (n = 7); and 0% after 48 hr (n = 8). (ii) Return of euglycemia was increasingly delayed with increasing preservation intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Cold-storage preservation of the canine and rat pancreas prior to islet isolation.

Cold-storage preservation of the canine pancreas prior to islet isolation has previously been noted to reduce the intrasplenic islet autograft success rate; but the mechanism of this deleterious effect has not been determined. We undertook a study in both outbred dogs and Lewis (RT1-1) rats to determine the influence of cold-storage preservation interval, preservation solution, and flushing technique on islet yield and islet viability. The preservation solutions used were those that had proved most efficacious in preserving segmental canine pancreases--namely, the modifications of silica gel fractionated plasma (SGF-III and SGF-IV) and an hydroxyethylstarch/lactobionate solution (UW-1). In the first set of experiments, the traditional vascular flush was used; this was followed by storage at 4 degrees C. After brief periods of preservation (3 hr in the rat, 12 hr in the dog) there was a significant (P less than 0.006) reduction in islet yield. The reduced yields were similar with each solution tested, were made worse with increasing intervals of storage, and resulted in a significant reduction in autograft success rate. The second set of experiments examined the effect of using an intraductal flush prior to preservation, along with the effect of adding collagenase to the preservation fluid. Islet yields were maintained at control values in both animal models using preservation intervals of up to 24 hr. These islet yields produced auto- or isograft success rates similar to those obtained by transplanting freshly obtained tissue; verifying adequate islet viability. We recommend that a pre-storage ductal flush technique be used for cold-storage preservation of the pancreas prior to islet isolation and transplantation.

Animals↗
PubMed1989

Long-term follow-up of a kindred with multiple endocrine neoplasia type IIA.

A kindred with multiple endocrine neoplasia type IIA was studied. In four of five fully documented cases, patients presented with adrenal medullary disease during the second or third decade; in three cases, medullary thyroid carcinoma was not diagnosed until the fourth decade. This kindred seems to have an aggressive variant of adrenal medullary disease in which clinical presentation is early, metastasis occurs, and oncological cure is uncommon. Early detection and operation were important, and symptoms were controlled with operations and alpha- and beta-adrenergic blockade in uncured members.

Adolescent↗
PubMed1989

Successful transplantation of canine islets of Langerhans after 24 hours cold-storage.

Utilizing the intrasplenic canine islet autograft model, it was possible to examine the effect of cold-storage of pancreatic tissue, both prior to and following dispersion, on functional outcome. A control group of dogs receiving freshly prepared autografts (n = 8) obtained durable euglycaemia in 75% of cases; the mean K value at two weeks being -1.70 (Standard Deviation (sd) = 0.06). In the first experimental group, animals (n = 8) were transplanted following 24 hours of whole pancreas cold-storage in silica gel fractionated plasma (SGF) using intraductal perfusion prior to preservation. None of these animals obtained euglycaemia; the transplanted material having a significantly reduced insulin content compared with controls (p = 0.0006). In the second experimental group, animals (n = 6) were transplanted following 24 hours of dispersed pancreatic tissue storage in SGF. This resulted in an 83% incidence of durable euglycaemia; the mean K value at two weeks being -1.60 (sd = 0.3). The glucose decay curve improved with time in this group and at three months the mean K value was -2.00 (sd = 0.38); this value being significantly superior to that of the control animals (K = -1.34, sd = 0.34, p less than 0.05). We conclude that while storage of the whole pancreas prior to islet isolation remains problematic, it is possible to reliably preserve dispersed pancreatic tissue for 24 hours by simple cold-storage, as assessed by the functional outcome of intrasplenic autografting in the dog model. These findings have important clinical implications.

Amylases↗
PubMed1988

Immunosuppressive activity of class I antigens in the absence of antigen-presenting cells that are MHC-compatible with the host.

Pretransplant transfusions of heat-treated spleen and lymph node cells were shown to prolong the survival of DA strain heart grafts in 3 allogeneic host strains: BS, HS, and AS2. To examine whether MHC incompatibility was necessary for immunosuppression mediated by heat-treated cells, AS strain skin-graft recipients were pretreated with fresh or heated inocula from either MHC compatible or incompatible congenic donor strains, AS2.1L(AS) and AS.1F(AS2) prior to transplanting donor strain skin. Prolonged survival was observed only in the MHC-incompatible strain combination, and in this MHC-incompatible strain combination, and in this instance heated cells were conspicuously more immunosuppressive than fresh cells. To determine the effect of intra-MHC differences between donor and host on graft survival, cells from a recombinant donor strain (r22), which shared class II antigens with the graft donor strain and class I antigens with the host, were transfused prior to heart transplantation. Neither fresh nor heated r22 cells prolonged graft survival. Our data accord with the suggestion that in the absence of MHC-compatible antigen-presenting cells, foreign class I antigen is immunosuppressive.

Animals↗
PubMed1988

Weight-corrected islet counts are predictive of outcome in the canine intrahepatic islet autograft model.

A combination of high-concentration collagenase digestion and density-gradient purification of canine pancreatic tissue made it possible to obtain relatively pure islets which could be quantified and the outcome of intrahepatic autotransplantation correlated with weight-corrected islet counts in the transplanted tissue. Of eleven dogs, seven achieved durable euglycaemia within 24 hours. All of these animals received islet doses of greater than 4,380 per kilogram of body weight. The remaining four animals became progressively hyperglycaemic necessitating sacrifice within one week; they all received islet doses of less than 4,380 per kilogram (p = 0.042). This model is therefore satisfactory for the investigation of preservation injury to islets and of allotransplantation because it identifies prospectively the transplants which ought to succeed, giving evidence for or against additional immune or ischaemic resistance to graft function.

Animals↗
PubMed1986

Trophoblastic metaplasia in urothelial carcinoma of the bladder.

Trophoblastic differentiation in bladder carcinoma is reported in four patients. Plasma gonadotrophin (beta subunit of HCG), measured in three patients, was elevated. In one patient treated with cisplatin, vinblastine and bleomycin, the beta HCG level fell significantly but progression of malignant disease was not arrested.

Adult↗
PubMed1981

To strip or not to strip the long saphenous vein? A varicose veins trial.

A double blind controlled trial of surgery for varicose veins was conducted on the legs of patients with bilateral symmetrical varicose veins. The two treatments, saphenofemoral ligation and avulsion of varices, with and without stripping of the long saphenous vein from ankle to groin, were randomly allocated among the legs of individual patients. At follow-up, between 2.5 and 3.5 years, an objective (observer) assessment was that stripping conferred a significant advantage, but the incidence of paraesthesia and pain biased patient's opinion against stripping.

Adult↗