Search PubMed⌕ Search

Biomedical subjects

J S Thompson

Publications and source records attributed to J S Thompson.

At least 19 recordsLinked to original sources
PubMed1995

The effect of human IL-2-activated natural killer and T cells on graft-versus-host disease and graft-versus-leukemia in SCID mice bearing human leukemic cells.

We have previously reported that xenogeneic lethal acute graft-versus-host disease (GVHD) was induced by transplantation of a mixture of human IL-2 activated natural killer (NK) and T cells into SCID mice conditioned with 4 Gy total-body irradiation (TBI), but not by IL-2-activated pure human T cells or NK cells. TBI and transplantation of the mixture of activated cells were both required to produce the lethal effect. We now report the effect of human IL-2 activated NK, T, or NK+T effector cells on the development of acute and chronic GVHD and GVL in SCID mice bearing human leukemic cells. Ten days after being inoculated i.v. with 2 x 10(7) human U-937 or K-562 leukemic cells, SCID mice, hereafter termed hu-leukemic mice, were radiated with 4 Gy TBI and transplanted i.v. with 5 x 10(7) human IL-2-activated NK, T, or NK+T effector cells. Hu-leukemic control mice received neither TBI nor effector cell transplantation. Acute GVHD-positive control SCID mice were transplanted with 5 x 10(7) H-2-incompatible C57Bl/6 splenocytes following 4 Gy TBI. The mice were observed for signs of GVHD and leukemia for 90 days. Twenty of 20 non-effector cell-transplanted control hu-leukemic mice developed signs related to leukemia and died with leukemic infiltration in the brain, liver, kidney, and lung 50-65 days after inoculation. Flow cytometry (FC) demonstrated 21-89% human leukemic cell infiltration in the bone marrow. Fourteen of 14 hu-leukemic mice transplanted with NK+T effector cells did not develop signs of advanced leukemia but died within 17 days of acute GVHD. FC demonstrated no human leukemic cells in their marrow. Twelve of 15 and 18 of 25 hu-leukemic mice transplanted with either NK or T cells survived 90 days without any evidence of symptomatic leukemia (P < 0.01 compared with non-effector cell-transplanted groups). NK-transplanted hu-leukemic animals experienced mild-to-moderate acute GVHD during the first 10-20 days posttransplantation, but gradually recovered and did not develop chronic GVHD. Hu-leukemic animals transplanted with T effector cells manifested no signs of leukemia or acute GVHD but chronic GVHD skin lesions appeared 80-90 days after transplantation. We conclude that acute GVHD, chronic GVHD, and GVL are associated but separable phenomena.

Animals↗
PubMed1995

Regional variation in canine intestinal muscle mass and function.

Our aim was to investigate the contribution of variations in intestinal muscle morphology or function to regional differences in motor properties in vivo. We quantitated intestinal muscle thickness and surface area along the canine gut and compared the in vitro contractile properties of the jejunum and ileum. The thickness and cross-sectional surface area of both circular and longitudinal muscle demonstrated a parabolic distribution along the intestine, with the greatest values occurring in the proximal and distal regions. The terminal ileum had the greatest circular (885 +/- 194 microns) and longitudinal muscle (367 +/- 135 microns) thickness. Circular muscle was 2.5-3 times thicker than longitudinal muscle at all points. Passive tension was similar in muscle strips from the mid-jejunum, mid-ileum, and terminal ileum (2.8 +/- 0.8, 2.5 +/- 0.4, and 2.3 +/- 0.8 vs 2.5 +/- 0.5, 1.9 +/- 0.5, and 2.8 +/- 1.0, longitudinal and circular, respectively). Active and total tension, however, were significantly greater in longitudinal than circular muscle in mid-jejunum (active; 8.5 +/- 1.4 vs 5.6 +/- 1.2, P < 0.05 and total 11.3 +/- 1.7 vs 8.1 +/- 1.2) and in mid-ileum (active 9.5 +/- 1.6 vs 5.8 +/- 1.2 and total 12.0 +/- 1.6 vs 7.7 +/- 1.2). Values for each layer were similar in both sites. In contrast, in the terminal ileum, longitudinal and circular muscle strips demonstrated similar active (10.1 +/- 1.7 vs 9.0 +/- 2.7, NS) and total tension (12.4 +/- 2.0 vs 11.9 +/- 3.4, NS). Dose-response curves to carbachol (10(-8)-10(-2) M) were similar in all these regions. We conclude (1) there are regional variations in muscle mass but contractile properties are similar in jejunum and ileum; and (2) the unique motor properties of the terminal ileum may be related more to differences in muscle morphology and neural input than intrinsic function.

Animals↗
PubMed1995

Edgar J. Poth Memorial Lecture. Surgical aspects of the short-bowel syndrome.

BACKGROUND: Surgeons are frequently confronted with patients with the short-bowel syndrome. Important surgical issues are maintaining intestinal continuity, treating complications, and performing procedures to improve intestinal function. METHODS: A comprehensive review of the English language literature and the author's own experience were employed to make recommendations about surgical management of the short-bowel syndrome. CONCLUSION: At the time of initial resection, ostomy formation is often prudent. The decision to restore continuity at a later time should balance anticipated functional outcome against potential complications. Several surgical strategies can be employed at reoperation in these patients to minimize further loss of intestine. Prophylactic cholecystectomy should be considered because of the increased risk of cholelithiasis. Gastric hypersecretion rarely requires operative therapy. Surgical therapy for the short-bowel syndrome includes procedures to slow intestinal transit, optimize intestinal function, and increase intestinal surface area. The choice of operation is influenced by intestinal remnant length and caliber and its function. Only a small proportion of patients are candidates for nontransplant procedures, of which intestinal lengthening is most efficacious. Intestinal transplantation, either alone or combined with the liver, is emerging as the most promising therapy in short-bowel syndrome.

Humans↗
PubMed1995

Surgical approach to short-bowel syndrome. Experience in a population of 160 patients.

OBJECTIVE: The authors reviewed their experience with short-bowel syndrome to define the surgical approach to this problem in 160 patients. METHODS: Forty-eight adults and 112 children were evaluated over a 15-year period. RESULTS: Seventy-one patients (44%) adapted to resection and took enteral nutrition alone. Forty-four patients (28%) were supported by parenteral nutrition (PN). Forty-five patients (28%) have had 49 surgical procedures. Fifteen patients with adequate intestinal length (> 120 cm in adults) but dilated dysfunctional bowel underwent stricturoplasty (n = 4) or tapering (n = 11). Thirteen patients (87%) demonstrated clinical improvement. Fourteen patients with shorter remnants (90-120 cm) and rapid transit time received an artificial valve (n = 2) or a reversed segment (n = 1). All patients' conditions improved initially, but the reversed segment was revised or taken down. Fourteen patients with short remnants and dilated bowel underwent intestinal lengthening. Twelve patients' conditions improved (86%), one underwent transplantation, and one died. Sixteen patients with very short remnants (< 60 cm) and complications of PN underwent solitary intestine (n = 4) or combined liver-intestinal transplantation (n = 13). One-year graft survival was 65%. There have been five deaths. CONCLUSIONS: The surgical approach to short-bowel syndrome depends on the patient's age, remnant length and caliber, intestinal function, and PN-related complications. Nontransplant procedures have a role in the treatment of selected patients. Intestinal transplantation is emerging as a potential therapy for patients with significant PN-related complications.

Adolescent↗
PubMed1995

Effect of blood and albumin on pulmonary hypertension and edema in perfused rabbit lungs.

Perfusate composition may alter pulmonary hemodynamics and edema formation in perfused lungs. Perfusion for 3 h with Krebs-Henseleit solution with 3% bovine serum albumin did not produce pulmonary hypertension, pulmonary edema (assessed by lung wet-to-dry wt ratio), or increased macromolecular permeability (assessed by 125I-albumin uptake). Addition of blood to hematocrit levels of 10 or 20% resulted in pulmonary hypertension during the final hour of perfusion but not pulmonary edema or increased macromolecular permeability. Pulmonary hypertension during blood perfusion was primarily due to increased precapillary resistance. Perfusion with buffer solution without albumin produced edema and increased macromolecular permeability but not pulmonary hypertension. In lungs perfused with blood (20% hematocrit), thromboxane B2 levels increased in parallel with the pulmonary hypertension, and inhibition of cyclooxygenase or thromboxane synthase with indomethacin or dazmegrel prevented pulmonary hypertension. Perfusion with leukopenic blood (from prior nitrogen mustard administration or from filtration) also prevented pulmonary hypertension. We conclude that blood perfusion produces pulmonary hypertension via thromboxane A2 generation, which depends on leukocyte activation, and that perfusion with buffer solutions without albumin produces edema and increased permeability without pulmonary hypertension.

Albumins↗
PubMed1995

Somatostatinoma: atypical presentation of a rare pancreatic tumor.

Somatostatinomas are rare neuroendocrine tumors that can result in a variety of symptoms depending on the secretion of other peptides in association with or in response to somatostatin. The rarity and variable clinical presentation of these tumors present problems in diagnosis and management. This report details the treatment of a 66-yr-old male who had a somatostatinoma with an atypical location and presentation. His clinical course was one of recurrent disease treated surgically and the interval development of cholelithiasis. He has survived 5 yr with his tumor, illustrating that monitoring peptide levels and an aggressive surgical approach are warranted for this condition. Prophylactic cholecystectomy should be considered at the time of exploration.

Aged↗
PubMed1992

The accelerated internal medicine program at the University of Kentucky.

Concern is growing about the ability of categorical medicine residency programs, structured within academic health centers, to provide balanced, progressive, postgraduate internal medicine education. Detrimental factors, including over-representation of critically ill patients, shortened length of hospitalization, stress, discontinuity between undergraduate and graduate training, rotational assignments driven by hospital service imperatives, and total costs, may all negatively affect internal medicine residency education. Therefore, an experimental accelerated internal medicine (AIM) curriculum combining 3 years of undergraduate with 3 years of graduate internal medicine education has been initiated by the Department of Medicine and the College of Medicine at the University of Kentucky. After completion of the third year and during the first 13 months of the AIM curriculum, selected students are rotated through an integrated series of educational experiences that incorporate all of the requirements for graduation from medical school and progressively advance the students' skills, knowledge, and responsibilities to that of a second-year resident. Thereafter, the curriculum is similar to that of the categorical residents, except that more ambulatory care and off-site rotations are interspersed to better provide the educational experiences representative of the practice of internal medicine. Evaluations of the first groups of AIM residents indicate that their performance has equaled that of the control residents who graduated after 4 years from the College of Medicine. Furthermore, the AIM residents report general acceptance by their fellow residents and attending physicians and report no undue stress in making the transition.

Costs and Cost Analysis↗
PubMed1992

Activation of human phagocytes through carbohydrate antigens (CD15, sialyl-CD15, CDw17, and CDw65).

The leukocyte carbohydrate (CHO) Ag CD15, sialyl-CD15, and CDw65 have recently been found to function as ligands for CD62 and ELAM-1 cell adhesion molecules on platelets and endothelium, respectively. Cell adhesion ligands also may act as receptors capable of signal transduction. We therefore investigated the possibility that these CHO Ag and CDw17, a glycolipid Ag whose expression is regulated by leukocyte activation, may have receptor-like characteristics. The effects of antibody cross-linking of CHO Ag on phagocyte activation were measured by using flow cytometry and fluorescent indicators for cytoplasmic calcium ions, oxidative burst, and the granule-associated proteins CD11b and CD67. Cross-linking of CD15, sialyl-CD15, CDw65, or CDw17 induced a moderate release of calcium ions into the cytoplasm of granulocytes, a strong activation of oxidative burst, and a low up-regulation of CD11b and CD67 compared to the effects of treatment with 4 microM FMLP. The results suggest a role for CHO Ag in leukocyte signal transduction and support the view that these molecules are involved in phagocyte activation.

Antibodies, Monoclonal↗
PubMed1992

Technique for revision of continent ileostomy.

A technique is described for revising an incompetent nipple valve of a continent ileostomy. The procedure involves preserving the incompetent valve and using it as a collar around the base of the new valve to improve function.

Adult↗
PubMed1992

Analysis of the Lewisx epitope in human pancreas and pancreatic adenocarcinomas.

The Lewisx epitope (Gal beta 1-4[Fuc alpha 1-3]GlcNAc-R) can be detected in most ductal pancreatic carcinomas. However, few data pertain to its expression in normal exocrine pancreas and its biochemistry. We compared the expression of the Lewisx epitope in normal pancreas with its expression in pancreatic adenocarcinomas and tumor cell lines and to further characterize the nature of the antigens bearing this epitope with immunochemical methods. On frozen tissue sections of normal pancreas, the Lewisx epitope was detected focally in acinar cell granules; sialosyl-Lewisx was detected in centroacinar cells and the cytoplasm of intralobular ducts. Sixteen of 19 pancreatic carcinomas expressed the Lewisx antigen on tissue sections; however, there was no correlation with prognostic parameters, such as tumor grade or stage. Eighteen of 19 tumor specimens were positive for sialosyl-Lewisx. Analysis of pancreatic carcinoma cell lines (CAPAN-1, CAPAN-2, and DAN-G) revealed intracytoplasmic expression of sialosyl-Lewisx epitopes in these cells, and cell surface reactivity was detected on flow cytometry for sialosyl-Lewisx. Lectin-affinity chromatography of cytoplasmac preparations showed that Lewisx-positive antigens of normal human pancreas bind to SBA and UEA-I lectins but have little or no affinity to WGA, GS-I, or DBA lectins, indicating the presence of Fuc and Gal oligosaccharide residues. It was concluded that the Lewisx and sialosyl-Lewisx antigens are nonpolymorphic carbohydrate determinants that are present in secretory granules of acinar cells, ductules, and pancreatic secretions. This makes the Lewisx antigen suitable for the analysis of the secretory process in the exocrine pancreas and the study of secretory differentiation antigens in ductal pancreatic carcinoma.

Adenocarcinoma↗
PubMed1992

Effect of a smooth muscle antagonist on contraction of patched intestinal defects.

Growing new intestinal mucosa on serosal patches may potentially increase intestinal surface area but is limited by contraction of the serosal patch. Since this might be related to smooth muscle contraction or altered collagen metabolism, our aim was to determine whether the smooth muscle antagonist thiphenamil inhibits contraction. Fifty rabbits had two 2 x 5-cm full-thickness intestinal defects patched with adjacent cecum. Group I (n = 25) received saline and Group II (n = 25) 0.02 M thiphenamil at 10 cc/hr intraluminally. Animals were sacrificed at 1, 3, 5, 7, and 10 days. Group II had significantly less contraction of the proximal patch until the 10th day after patching (84 +/- 8 vs 66 +/- 20% Day 1, 67 +/- 4 vs 52 +/- 9% Day 5, 42 +/- 14 vs 42 +/- 7% Day 10). Epithelialization of patches was significantly less in Group II animals at 10 days (88 +/- 8 and 86 +/- 11% vs 47 +/- 20 and 50 +/- 16%, P less than 0.05) but crypt cell production rate and villus height were similar. The hydroxyproline content of regenerating tissue increased significantly 7 and 10 days after patching but was similar in the two groups (30.8 +/- 5.9 micrograms/mg tissue Day 10 vs 12.8 +/- 2.8 Day 1). Smooth muscle antagonism by thiphenamil inhibited contraction of serosal patches but had a deleterious effect on epithelialization and mucosal enzyme activity. The transient effect of thiphenamil and the associated increase of hydroxyproline content suggest that collagen may have the predominant role in contraction.

Animals↗
PubMed1992

Quality assurance and morbidity and mortality conference.

Many surgeons assert that Morbidity and Mortality (M & M) conference in itself assures an effective quality assurance (QA) program. Recent emphasis on QA in other sectors has resulted in other processes for evaluating quality of care. The goals of QA programs are to identify adverse patient care events, relate these to specific physicians and use this information to improve patient care, and for credentialing and privileging physicians. Our aim was to determine the role of surgical M & M conference in a QA program which also includes occurrence screening, wound infection surveillance, and surgical case review. The weekly M & M conference is a discussion of identified complications and deaths submitted voluntarily by surgeons. During a 2-year period 5755 procedures were associated with 255 complications and 82 deaths. Only 74% of events identified by occurrence screening, 35% of cases identified by surgical case review, and 54% of wound infections had been submitted to M & M conference. Seventy-four percent of surgical residents and 33% of staff surgeons were present at M & M conference when their complications were discussed. Level of care (I, accepted practice; II, may have managed differently; and III, would have managed differently) was assessed for each complication at M & M conference and by peer review of the medical record for occurrence screening.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1992

Serosal patching impairs intestinal adaptation following enterectomy.

Increasing intestinal absorptive surface by mucosal regeneration on serosal patched intestinal defects is a potential surgical treatment for the short bowel syndrome. We previously found in long-term studies that serosal patching in dogs undergoing 75% enterectomy was deleterious to intestinal adaptation and absorption. Our aim was to evaluate the effect of serosal patching on the early morphologic and functional changes in postresectional adaptation and to examine the role of polyamine metabolic pathways in this process. Five unoperated New Zealand white rabbits (GP I) served as controls. Twelve other rabbits underwent either 50% distal enterectomy alone (GP II) or simultaneously had two 2 x 5-cm full-thickness ileal defects patched with adjacent cecal serosa (GP III). Animals in GP II gained an average of 7.2 +/- 5.3% body weight, whereas GP III animals lost 5.6 +/- 9.0% body weight (P less than 0.05). Intestinal remnant length was significantly less in GP III 3 weeks postoperatively (66 +/- 11 vs 85 +/- 8 cm, P less than 0.05) as was mucosal protein content (4.1 +/- 1.8% vs 6.2 +/- 1.9%) but villus height was similar in GPs II and III (505 +/- 131 vs 508 +/- 110 microns). In vitro mucosal function was similar in all three groups. Crypt cell production rate was significantly lower while ornithine decarboxylase and diamine oxidase activity were higher in GP III compared to GP II. However, polyamine levels were similar in all three groups. Serosal patching impairs intestinal adaptation following massive enterectomy. This is due in part to a decrease in proliferative activity which is not directly related to altered polyamine levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1992

Basement membrane components enhance isolated enterocyte growth.

Isolated enterocyte transplantation may have a potential role in increasing intestinal surface area. However, enterocytes are notoriously difficult to grow. Basement membrane components (BMC) promote adherence, migration, and differentiation of enterocytes. Our aim was to determine if BMC enhance enterocyte growth. Twenty-nine rabbits had 5-cm ileal segments resected and serosal pouches (n = 22) created from the serosal surface of the colon. Harvesting of enterocytes by warm trypsinization resulted in 92 +/- 6% cell viability and yielded 5.0 +/- 2.4 10(6) enterocytes/cm intestine. Enterocytes (10(5) were cultured in vitro (n = 7) in 10 ml growth media in plain flasks and flasks coated with laminin alone or Matrigel (an extract of mouse basement membrane containing laminin plus Type IV collagen and heparan sulfate). The cells were subcultured at 2 weeks and examined after Geimsa staining at 4 weeks. Epithelial growth was confirmed by light microscopy and staining for cytokeratin and quantitated by image analysis (JAVA). Epithelial coverage of the flasks was greater with Matrigel (80 +/- 15%) than laminin (66 +/- 15%) which was greater than control (44 +/- 20%) (P less than 0.01). For in vivo studies 10(5) harvested cells were infused into the serosal pouches either in growth media (n = 9) or media + Matrigel (n = 13). Epithelial growth in the pouch was evaluated by qualitative scoring of cytokeratin staining. Cytokeratin staining was similar on control colon serosa (n = 5) and serosa after infusion of cells in media alone. However, Matrigel significantly enhanced the area, depth, and intensity of staining.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Association of radiolabeled urogastrone binding with regenerating intestinal mucosa and epidermal growth factor/urogastrone producing organs in rat.

In the present study, we have tested the hypothesis that the regeneration of intestinal epithelium is regulated by changes in the uptake of radiolabeled recombinant human urogastrone (125I rhUG) in the regenerating mucosa and epidermal growth factor/urogastrone (EGF/URO) producing organs in the rats. Operations were performed on rats to approximate the ileal mucosa to the serosal surface of the cecum. This procedure allows the regeneration of ileal mucosa onto the serosal surface of the cecum. Groups of 5 rats were killed on the 2nd, 4th, 8th and 12th post-operative days. Two hours before autopsy, rats were given 0.5 ml (50 microCi with 30 micrograms protein) of 125I rhUG intravenously and the following tissues were removed: regenerating mucosa, salivary gland, duodenum, liver and kidney. Results indicated that the uptake of 125I rhUG was significantly greater in the salivary gland and duodenum on the 2nd post-operative day which gradually tapered with increasing time after surgery. A similar pattern in the uptake of 125I rhUG was also evident in the regenerating mucosa. Further analysis revealed a significant correlation between the uptake of 125I rhUG in the salivary gland and duodenum vs rate of epithelialization and uptake of 125I rhUG in the regenerative mucosa. These results suggested that the endogenous EGF/URO produced in the salivary gland and duodenum may be a factor in the regulation of intestinal regeneration; however, the mechanism responsible for reflex stimulation of EGF/URO production in these organs is not known.

Animals↗