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Biomedical subjects

J S Thompson

Publications and source records attributed to J S Thompson.

At least 109 records · Page 6Linked to original sources
PubMed1995

Epithelial cell proliferation and biodistribution of radiolabeled urogastrone in the gastrointestinal mucosa of young and old mice.

We have evaluated epithelial cell proliferation and biodistribution of radiolabeled recombinant human urogastrone/epidermal growth factor (125I rhUG/EGF) in the gastrointestinal mucosa of young (2+ months) and old (30+ months) mice. Animals were injected intraperitoneally with the metaphase arrest agent vincristine sulfate and intravenously with 125I rhUG/EGF. Animals were killed after two hours. Crypt cell production rate and uptake of radiolabeled urogastrone were measured in the same intestinal tissues. The results demonstrated that older animals had significantly greater crypt cell production rate as compared to young. However, the uptake of 125I rhUG/EGF was not significantly different (except in duodenum, where the uptake of 125I rhUG/EGF was significantly greater in young compared to old animals) between young and old animals. This suggests that increased epithelial cell proliferation in the aging animals is not associated with increased uptake of 125I rhUG/EGF. Thus epidermal growth factor/urogastrone may not be a primary factor for the intestinal kinetic differences which exist between young and old animals.

Aging↗
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

Effect of intestinal tapering and lengthening on intestinal structure and function.

BACKGROUND: Intestinal lengthening (TL) is increasingly performed for the short bowel syndrome. Our aim was to evaluate the effect of TL on canine intestinal structure and function. METHODS: Two groups of 5 dogs had 75% distal intestinal resection. Twelve weeks later, serosal electrodes were placed in one group (RO) and tapering and lengthening of 10 to 15 cm distal intestine and electrode placement was performed in the other group (TL). Nutritional status and intestinal absorption, motility, and hormone release were assessed every 4 weeks for 12 weeks after the second procedure. RESULTS: The animals with the lengthening had diminished body weight (75% +/- 2% versus 81% +/- 4%, P < 0.05) and albumin levels (2.4 +/- 0.2 g/dL versus 2.9 +/- 0.5 g/dL, P < 0.05) and impaired absorption (stool fat 18% +/- 6% versus 10% +/- 3%, P < 0.05) compared with those that had undergone resection alone. The intestinal adaptive response was blunted in the TL group (villus height 328 +/- 90 microns versus 410 +/- 36 microns, P < 0.05). Transit time was prolonged 4 and 8 weeks (19 +/- 6 min and 18 +/- 5 min, respectively, versus 11 +/- 3 min, P < 0.05) after TL. Myoelectrical recordings showed a drop in slow wave frequency and impaired migration of Phase III of the migrating motor complex within the tapered and lengthened segments (P < 0.05). Both fasting and postprandial serum gastrin levels were two times greater in the TL group (P < 0.05). Enteroglucagon levels were increased after resection alone; this increase was attenuated by more than 50% in the TL group (P < 0.05). The somatostatin response to feeding was substantially greater in the TL animals. CONCLUSIONS: TL impairs nutritional status and intestinal absorption and adaptation following massive resection. The changes in absorption and transit may be related, in part, to motor disruption and hypergastrinemia. The impaired adaptation is possibly related to decreased enteroglucagon and increased somatostatin levels.

Animals↗
PubMed1995

Strategies for success in academic surgery.

BACKGROUND: A growing concern among university surgeons is a perceived threat to the traditional academician role. Factors that have led to this concern include (1) changes in reimbursement and patient referral patterns, both of which have resulted in reduced income; (2) mounting external pressure from the departmental chairperson/dean to generate professional fees; (3) pervasive ambiguity in the criteria for promotion and tenure; (4) intensified competition for research dollars in recent years; and (5) a perception that fellow academicians view surgeons as operating room technicians incapable of laboratory research. These cogent issues have the means to place academic goals in jeopardy. Potentially they lead to dissatisfaction, unhappiness, and eventual departure from academia. A healthy solution to the problem includes departmental recognition and reward for whichever primary role/s the academic surgeon embraces--clinical, educational, research, or administrative. Clear chairperson-faculty communication on the issues of expectation and reward is a key ingredient in the solution. METHODS: A mail survey was conducted with chairpersons of surgical departments and academic surgeons addressing the issues of retention, promotion, and benefits. RESULTS: Results revealed significant differences in perceptions, suggesting the need for improved communication between faculty and chairpersons and a team approach to help maintain academic viability in the future. CONCLUSIONS: When the quadruple threat can be mutually described as a departmental rather than individual quality, the joys and rewards of academic surgery can be considerable for faculty and chairpersons alike.

Academic Medical Centers↗
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↗
PubMed1995

The intestinal response to critical illness.

Critical illness is characterized by the presence of several factors that can cause marked alterations in the structure and function of multiple organ systems (1-2). These factors include injury, ischemia, sepsis, and starvation (Fig. 1). It is common for more than one of these problems to be present in the individual patient. Our current understanding of the effect of these various factors on intestinal structure and function has increased markedly during the past decade (3). Furthermore, the patterns of intestinal dysfunction that occur in response to these conditions have also been better characterized. Although malabsorption and motility disorders have long been recognized as clinical problems, more recently loss of intestinal barrier function and immune dysfunction have gained attention. This improved understanding of the response of the intestine to critical illness may lead to prevention of intestinal failure or permit more specific therapy when it occurs. The goals of this manuscript are to describe the response of the small intestine to critical illness and to identify potential therapeutic strategies for preventing and treating intestinal failure in this setting.

Critical Illness↗
PubMed1994

Histone H3 amino terminus is required for telomeric and silent mating locus repression in yeast.

Heterochromatin is a cytologically visible form of condensed chromatin capable of repressing genes in eukaryotic cells. For the yeast Saccharomyces cerevisiae, despite the absence of observable heterochromatin, there is genetic and chromatin structure data which indicate that there are heterochromatin-like repressive structures. Genes experience position effects at the silent mating loci and the telomeres, resulting in a repressed state that is inherited in an epigenetic manner. The histone H4 amino terminus is required for repression at these loci. Additional studies have indicated that the histone H3 N terminus is not important for silent mating locus repression, but redundancy of repressive elements at the silent mating loci may be responsible for masking its role. Here we report that histone H3 is required for full repression at yeast telomeres and at partially disabled silent mating loci, and that the acetylatable lysine residues of H3 play an important role in silencing.

Amino Acid Sequence↗
PubMed1994

Effect of total body irradiation, busulfan-cyclophosphamide, or cyclophosphamide conditioning on inflammatory cytokine release and development of acute and chronic graft-versus-host disease in H-2-incompatible transplanted SCID mice.

In a previous study, we found that total body irradiation (TBI) was essential to induce acute graft-versus-host disease (GVHD) after allogeneic H-2-incompatible splenocyte (SP) transplantation in SCID mice. SCID mice (H-2d) conditioned with cyclophosphamide and transplanted intravenously (IV) with 5 x 10(7) C57BL/6 (H-2b) SP developed chronic GVHD within 3 months posttransplant without any evidence of preceding acute GVHD. In this study, SCID mice were conditioned with 4 Gy TBI or non-TBI regimens, either BuCy2 (busulfan 4 mg/kg/d + cyclophosphamide 100 mg/kg/d for 2 days) or Cy5 (cyclophosphamide 100 mg/kg/d for 5 days), and then transplanted IV with 5 x 10(7) SP. The TBI-conditioned mice were further divided into tree transplant groups: (1) TBI and SP administered the same day (TBI + D0 SP), (2) SP administered 4 days post-TBI (TBI + D4 SP), and (3) SP administered 7 days post-TBI (TBI + D7 SP). The severity of GVHD was compared among these groups by clinical and histologic grading. Twenty-eight of 28 mice treated with TBI + D0 SP died of acute GVHD, with overwhelming diarrhea by day 15 posttransplantation. Sixteen mice treated with either TBI + D4 SP or TBI + D7 SP developed acute GVHD, but none of them died of this disorder during 30 days posttransplantation. The mice conditioned with non-TBI regimens developed chronic GVHD within 3 months without showing any detectable signs of acute GVHD. Serum and in situ colonic cytokines were determined by enzyme-linked immunosorbent assay and immunohistology respectively. TBI itself significantly increased both serum and colonic tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), and IL-6 when compared with non-TBI regimens and normal controls. TNF-alpha appeared in the serum and colon 4 hours post-TBI and peaked in 24 hours, followed by increasing IL-1 alpha and then IL-6 levels. TNF-alpha and IL-1 alpha decreased rapidly within 3 to 5 days post-TBI if no allogeneic cells were transplanted. Histoincompatible transplantation augmented cytokine release, which remained elevated on day 10 in these animals. Mice treated with TBI + D0 SP developed the most severe acute GVHD and had the highest levels of TNF-alpha, IL-1 alpha, and IL-6. The BuCy2-conditioned mice had the lowest cytokine levels and developed no acute GVHD. When the mice transplanted with TBI + D0 SP were treated immediately with recombinant soluble human TNF receptor (rhuTNFR:Fc) 100 micrograms/d intraperitoneally and for the subsequent 15 days acute GVHD mortality was significantly reduced from 100% to 50% (P < .001).(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1994

Effects of jejunoileal autotransplantation on gastrointestinal regulatory peptides.

Plasma gastrointestinal hormones were measured before and during feeding in eight dogs, more than one year after total autotransplant of the entire jejunoileum, and in controls. At sacrifice, tissues were taken from the transplanted segment and intact bowel for measurement of hormone and enteric neuropeptide content. Gastrin levels were reduced in autotransplanted dogs (fasting 63% of control, incremental response 67% of control, both P < 0.05), reflecting the loss of acid inhibitory reflexes. Secretin and cholecystokinin responses were identical between the two groups. Postprandial levels of gastric inhibitory peptide (incremental response 175% of control, P < 0.005), insulin, and peptide YY (158% of control, P < 0.05) were elevated following denervation, the former suggesting more rapid gastric emptying while the latter may reflect malabsorption. The neurotensin meal response was obtunded by denervation (incremental response 43% of control, P < 0.05), providing evidence for a neural pathway for its release. Pancreatic polypeptide responses were identical between the groups, suggesting intact pancreatic innervation. Abnormal hormone secretion may contribute to the impaired fed motor responses seen following extrinsic denervation of the small bowel. In contrast, the neuropeptide content of the autotransplanted small intestine is normal, suggesting that extrinsic denervation has no long-term effects on peptide content of the enteric nervous system.

Animals↗
PubMed1994

Effects of artificial ileocolonic sphincter on motility in intestinal remnant following subtotal small intestinal resection in the dog.

We studied the effects of a sphincter substitute on motility in the intestinal remnant following an extensive distal intestinal resection. Two groups of adult dogs were studied; each underwent a 75% resection of the distal small intestine, and in one group a nipple valve was fashioned at the distal end of the remnant. Nutritional status, absorptive function, motility, and transit were studied over a three-month period. While the nipple valve animals had less diarrhea, steatorrhea, and hypoalbuminemia, motor activity and transit were similar in both groups. Thus, in both groups, fasting motor activity was dominated by clusters of phasic pressure activity. (Cluster frequency, per hour, mean +/- SE, resection vs resection with nipple valve: 4.8 +/- 1.05 vs 3.58 +/- 0.54, NS). We conclude that the beneficial effects of a sphincter substitute in ameliorating the short bowel syndrome in this dog model are not related to any modification of the motor response to resection but may simply reflect those of a low-grade mechanical obstruction.

Animals↗
PubMed1994

Practice environment and resident operative experience.

An important aspect of resident training is a graduated increase in responsibility and experience. The level of resident participation in operative procedures is influenced by many factors. Our aim was to determine the effect of the practice environment and staff perception of required surgical skills on the assignment of resident operative responsibility. Questionnaires were sent to 100 surgeons affiliated with the Department of Surgery at the University of Nebraska Medical Center, and the completion rate was 72%. Data were collected on the practice environment of the surgeons and their perception of appropriate resident level and required skills for performance of 20 common general surgery procedures. Surgeons in private practice (n = 34) and affiliated hospitals (n = 15) were more likely to assign cases to higher level residents than those at the University Hospital (n = 23) (mean: 3.0 +/- 0.5 and 3.0 +/- 0.3 versus 2.7 +/- 0.3 years, P < 0.05). Surgeons more than 15 years out of training (n = 28) were more likely to assign a higher level resident to procedures than those (n = 44) more recently trained (3.1 +/- 0.5 versus 2.7 +/- 0.3 years, P < 0.05). Surgeons who worked regularly with residents (n = 44) were more likely to assign a lower level resident to a given procedure (2.8 +/- 0.3 versus 3.1 +/- 0.5 years, P < 0.05). Multivariate analysis, however, found that only time since training was an important factor in the assignment of responsibilities. Laparoscopic procedures caused the greatest disagreement and were more likely to be assigned to higher level residents than the corresponding open procedures (hernia repair 3.3 +/- 0.1 versus 1.2 +/- 0.1 and cholecystectomy 3.2 +/- 0.1 versus 2.0 +/- 0.9 years, P < 0.05). Anatomy (46%) and judgment (36%) were most commonly considered the important surgical factors in determining operative responsibility. However, there was no correlation between assignment of operative responsibility and the perception of required skills for each surgeon. Thus staff perception of the appropriate resident level to perform general surgery procedures is more heavily influenced by factors in the practice environment than surgical aspects of the procedure.

Attitude of Health Personnel↗
PubMed1994

Clinical and lymphocyte responses to beta-carotene supplementation in 11 HIV-positive patients with chronic oral candidiasis.

Eleven HIV-positive patients with chronic oral candidiasis were supplemented with 60 to 120 mg of beta-carotene daily for 3 to 7 months. Lymphocyte profiles were evaluated at intervals to help assess immune competence. Although there was a modest increase in some lymphocyte values at 2 months, there was a significant decrease in numbers of CD4 and CD8 cells and CD4 percentage of lymphocytes after 6 months of beta-carotene supplementation. Serum triglyceride and liver enzyme levels were not affected by the beta-carotene supplementation. No improvement was observed in the control of the oral candidiasis. Under the conditions of the study, there was no indication that daily beta-carotene supplements enhanced immune competence or was of benefit in managing oral candidiasis.

AIDS-Related Opportunistic Infections↗
PubMed1994

Pancreaticoduodenectomy for suspected but unproven malignancy.

BACKGROUND: Pancreaticoduodenectomy is an accepted surgical option for certain benign conditions and biopsy proven cancer. Whether this procedure should be performed when malignancy of the pancreas and periampullary region is suspected but not confirmed represents a fairly common intraoperative dilemma. PATIENTS AND METHODS: Sixty-seven patients who had undergone pancreaticoduodenectomy during a 15-year period were evaluated retrospectively. RESULTS: The indications for resection were symptomatic benign conditions (n = 10, 15%), proven pancreatic or periampullary cancer (n = 37, 55%), and suspected but unproven malignancy (n = 20, 30%). The patients with suspected malignancy ranged in age from 27 to 73 years. Common findings in this group were abdominal pain (75%), jaundice (70%), weight loss (65%), and alcohol use (45%). There were 14 pancreatic and 6 ampullary masses. Biopsies obtained preoperatively (n = 15) and intraoperatively (n = 11) were nonconfirmatory. Postoperatively 9 patients (45%) were found to have tumors, including 6 pancreatic adenocarcinoma, 2 duodenal adenocarcinoma, and 1 islet cell tumor. Six of the 8 adenocarcinomas (75%) were stage I. Seven patients were alive 11 to 108 months later. The most common benign diagnosis was pancreatitis. There were 8 complications and 1 death. CONCLUSIONS: Pancreaticoduodenectomy performed based on suspicion alone frequently reveals malignancy. Immediate and long-term outcomes are acceptable. These findings justify a continued aggressive approach to suspected pancreatic and periampullary malignancy.

Adult↗
PubMed1994

Is there a prognostic difference between functional and nonfunctional islet cell tumors?

BACKGROUND: Pancreatic islet cell tumors are categorized as either functioning or nonfunctioning. Functioning islet cell tumors (FIT) elaborate a variety of hormones, producing dramatic symptoms, while the initial presentation of non-functioning islet cell tumors (NIT) is commonly an abdominal mass or symptom complex related to invasion of adjacent structures. As a result, NIT are purported to present at a later stage, with lower resectability rates, and an overall poorer prognosis, when compared to FIT. In addition, a number of reports have indicated that the incidence of NIT has increased significantly in recent years. PATIENTS AND METHODS: Twenty-eight patients were studied retrospectively. All had islet cell tumors of the pancreas and were seen at the University of Nebraska Medical Center and affiliated Nebraska Methodist Hospital during a 19-year period. RESULTS: There were 9 patients (32%) in the NIT group and 19 (68%) in the FIT group. The mean ages at presentation were 61 years for the NIT and 52 years for the FIT group. In the NIT group, all presented with either abdominal pain (n = 7) or jaundice (n = 2). In contrast, over 90% of the patients with FIT had symptoms referable to the specific hormone elaborated by the tumor. Primary tumor size for NIT was 4.1 +/- 0.7 cm versus 5.0 +/- 0.6 cm for the FIT group. No significant difference was found for NIT versus FIT with respect to the incidence of metastatic disease at presentation (44% versus 53%), resectability rate with curative intent (44% versus 53%), or disease-free survival at 2 years (67% versus 40%). CONCLUSIONS: This series, in contrast to earlier reports, suggests that nonfunctioning islet cell tumors do not present at a more advanced stage, have lower resectability rates, or an overall poorer long-term prognosis when compared to functioning tumors.

Adenoma, Islet Cell↗
PubMed1994

Effects of the neutral endopeptidase inhibitor, SCH 42495, on the cardiovascular remodelling secondary to chronic hypoxia in rats.

1. We have investigated the effects of inhibition of neutral endopeptidase on the cardiovascular remodelling secondary to chronic hypoxia in rats using a novel neutral endopeptidase inhibitor, SCH 42495. 2. Rats were divided into four groups, two of which were maintained in a normobaric, hypoxic chamber (10% O2) and two in room air. Animals received either neutral endopeptidase inhibitor, SCH 42495 (30 mg/kg), or aqueous methyl cellulose vehicle (0.4%) twice daily by oral gavage. 3. At 1, 3, 7, 10 and 14 days, animals (n = 4 per group for days 1, 3, 7 and 14, and n = 8 for day 10) were killed. Hearts were dissected and weighed for determination of ventricular ratios, lungs were perfused with formol saline for histological examination of the pulmonary vasculature, and blood was collected for measurement of plasma atrial natriuretic peptide level. 4. Treatment with SCH 42495 caused a significant reduction in the pulmonary vascular remodelling and ventricular hypertrophy in hypoxic rats after 10 days. Plasma atrial natriuretic peptide levels were significantly elevated in both SCH 42495-treated and control hypoxic animals (n = 8) after 10 days when compared with the normoxic groups. However, there was no difference in plasma ANP levels between SCH 42495-treated and control hypoxic groups at day 10. 5. Treatment with SCH 42495 leads to a decrease in cardiovascular remodelling secondary to chronic hypoxia in rats. A local action of atrial natriuretic peptide within the pulmonary vasculature may be responsible for this effect. Modulation of atrial natriuretic peptide may have therapeutic potential in the management of conditions characterized by pulmonary hypertension and pulmonary vascular remodelling.

Animals↗