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Biomedical subjects

J S Thompson

Publications and source records attributed to J S Thompson.

At least 163 records · Page 9Linked to original sources
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↗
PubMed1992

Effects of SCH 34826, a neutral endopeptidase inhibitor, on hypoxic pulmonary vascular remodelling.

Atrial natriuretic peptide (ANP) is a potent vasodilator of hypoxia constricted pulmonary vessels. Chronic infusions of ANP have been shown to limit the anatomical pulmonary vascular remodelling associated with chronic exposure to a 10% oxygen environment. SCH 34826 elevates plasma ANP by inhibition of the enzyme neutral endopeptidase EC 3.4.24.11. We administered by subcutaneous injection 90 mg/kg SCH 34826 twice daily into six male Wistar rats. Six littermate controls received 1 ml of 0.4% aqueous methyl cellulose vehicle. All animals were exposed to a 10% oxygen environment for 2 weeks. Administration of SCH 34826 caused a significant reduction in the hypoxia-induced pulmonary vascular remodelling and right ventricle hypertrophy. Neutral endopeptidase inhibition by drugs such as SCH 34826 could prove useful in conditions characterized by pulmonary hypertension and pulmonary vascular remodelling.

Analgesics↗
PubMed1992

Reoperation in patients with the short bowel syndrome.

The clinical courses of 53 adult patients with the short bowel syndrome (SBS) were evaluated to determine the incidence of and indications for reoperation. Mesenteric vascular disease (23 patients) and malignancy/irradiation (18 patients) were the most frequent causes of resection. Early reoperation was necessary in nine (17%) patients, primarily for intestinal complications. Twenty (53%) of the 38 patients leaving the hospital required a later abdominal procedure during the mean follow-up of 30 months (range: 2 to 108 months). Three (33%) of nine patients with ulcer disease had gastric resection. Six (21%) of 28 patients at risk for cholelithiasis developed symptoms. Four of these patients underwent cholecystectomy, and three others had a prophylactic cholecystectomy. Ten patients underwent ostomy closure or formation. Intestinal disease necessitated stricturoplasty (three), serosal patch (one), minimal resection (three), or takedown of an ileal conduit (one). Twenty-four (63%) of 38 patients with SBS received home total parenteral nutrition for a mean of 22 months (range: 2 to 105 months). Eleven patients required more than 1 vascular access procedure, and 4 had more than 3 procedures. Patients with the SBS frequently require reoperation for intestinal conditions, cholelithiasis, peptic ulceration, and vascular access. Prophylactic cholecystectomy and strategies for preserving intestinal length are important considerations in these patients.

Adult↗
PubMed1992

Short bowel syndrome.

With utilization of the techniques discussed in this review, patients with short bowel syndrome can be expected to live prolonged lives, even after fairly massive resection. Advances in parenteral and home parenteral nutrition and changes in the long-term management of chronic complications have altered the lifestyles of patients with short bowel syndrome. Intestinal transplantation may become an effective mode of therapy within a short period of time. Many surgeons faced with the possibility of leaving a child with only 10-15 cm of bowel in the past have closed the abdomen with the dead bowel and let the child die. These recent advances raise interesting ethical dilemmas. Research into the process of intestinal adaptation as well as greater experience with intestinal transplantation and other modes of therapy may further improve prognosis.

Animals↗
PubMed1992

Treatment of acute cellular rejection with T10B9.1A-31 or OKT3 in renal allograft recipients.

T10B9.1A-31, a nonmitogenic immunoglobulin Mk monoclonal antibody that detects an epitope on the alpha/beta chains of the T cell antigen receptor (TCR alpha/beta), or OKT3, an anti-CD3 mAb, was employed in a randomized double-blind phase II clinical trial to treat biopsy-proven acute cellular renal allograft rejection. Two of the 40 patients initially selected for the protocol were considered to be nonevaluable. Analysis of the remaining 38 patients receiving both living related and cadaveric donor allografts revealed a patient survival of 100% and a graft survival of 97%. Primary rejection reversal was achieved in 18/19 (95%) patients treated with T10B9.1A-31 and in 20/21 (95%) of patients receiving OKT3. The two patients who did not respond to the first mAb responded to the crossover mAb. Rerejection occurred in 3/18 (17%) of patients treated with T10B9.1A-31 and in 3/20 (15%) treated with OKT3. The mean day of rejection reversal was 1.9 +/- 0.7 with T10B9.1A-31 and 3.37 +/- 1.21 with OKT3 treatment. The rise in mean serum creatinine after mAb administration and the mean creatinine on days 1 through 6 were significantly less in patients treated with T10B9.1A-31. Biopsy specimens analyzed for rejection revealed no significant difference between the T10B9.1A-31 and OKT3 cohorts. The mean serum creatinines at 30, 60, 180, and 360 days posttransplantation were the same for both groups. Significantly fewer febrile, respiratory, and untoward effects followed the first dose (day 0) and fewer febrile, gastrointestinal, and neurological side effects occurred with subsequent doses (days 1-9) in patients treated with T10B9.1A-31. Infectious complications occurred in 3/13 patients treated only with T10B9.1A-31, in 9/17 OKT3-treated patients, and in 4/8 patients treated with both mAb. Analysis of human antimouse antibody (HAMA) revealed that the development of HAMA with T10B9.1A-31 was similar to that of OKT3.

Adult↗
PubMed1992

Factors affecting in vitro growth of harvested enterocytes.

Selective enterocyte transplantation may be an alternative to whole organ transplantation for increasing absorptive capacity. Our aim was to determine the effect of initial cell number and viability, proportion of intact crypts, and basement membrane components (BMC) on the in vitro growth of rabbit enterocytes. Enterocytes were harvested using warm trypsinization from ileal segments in 40 rabbits. Initial cell viability was 92 +/- 4% (mean +/- SD), cell yield was 7.7 +/- 3.6 x 10(6) cells/cm, and there were 0.51 +/- 0.33 crypts/100 cells. Initial cell viability correlated with cell yield (r = -0.508, p < 0.001) and % crypts (r = 0.313, p < 0.05). Cell yield also correlated with % crypts (r = -0.645, p < 0.001). Enterocytes (5 x 10(6)) were incubated in growth media in plain or BMC coated growth culture vessels for 14 days. There was a correlation between both number of cells seeded (r = 0.824, p < 0.001) and cell viability (r = -0.696, p < 0.01) and % growth colonies containing epithelial cells at 14 days. Both total growth colonies (r = -0.565, p < 0.05) and colonies with epithelial cells (r = -0.589, p < 0.05) had a negative correlation with % crypts. Incubating cells in BMC coated vessels (n = 6) resulted in significantly more dispase liberated cells after 14 days than in plain vessels (n = 6) (6.6 +/- 1.1 vs. 3.8 +/- 1.0 x 10(6), p < 0.05) but viability was similar (97 +/- 2% vs. 96 +/- 2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Amine Oxidase (Copper-Containing)↗
PubMed1992

Role of epidermal growth factor in intestinal regeneration.

We have quantitated uptake of radiolabeled recombinant human urogastrone/epidermal growth factor (125I rhUG/EGF), crypt cell production rate, and rate of epithelialization on days 2, 4, 8, and 12 after operation in the ileum, mucosa adjacent to the wound, and neomucosa (regenerating mucosa) during healing of a full-thickness ileal defect in rats. The uptake of 125I rhUG/EGF in adjacent mucosa and neomucosa was highest on the day 2 (0.64% +/- 0.1% and 0.98% +/- 0.14% injected dose/gm 125I rhUG) and significantly decreased by postoperative day 8. The crypt cell production rate in the adjacent mucosa and neomucosa (23.8 +/- 4.2 and 21.9 +/- 2.1 cells/crypt/hr) peaked on the postoperative days 4 and 8, respectively. The epithelial cell migration rate was increased significantly in the neomucosa on the day 2 (33 +/- 2 mm/day) and tapered gradually until postoperative day 12 (14 +/- 1 mm/day). A linear correlation was evident between the rate of epithelialization and uptake of 125I rhUG/EGF in the neomucosa (r = 0.93; p less than or equal to 0.05). These findings suggest that epithelial cell migration occurs earlier than cell proliferation during regeneration of intestinal epithelium and is closely associated with changing concentration of 125I rhUG/EGF in the neomucosa. This suggests that endogenous EGF may play an important role in intestinal regeneration.

Animals↗
PubMed1992

Reconstruction of the insensate thumb by neurovascular island transfer.

A carefully planned and performed interdigital neurovascular island transfer offers the potential of excellent vascularized sensate coverage for the thumb. The procedure has stood the test of time and remains an important procedure in the armamentarium of the reconstructive hand surgeon.

Humans↗
PubMed1992

Selective versus routine antibiotic use in acute appendicitis.

Whether prophylactic antibiotics should be employed routinely in all patients with presumed appendicitis rather than be administered selectively to those with suspected perforation remains a controversial issue. The outcome of 312 adult patients undergoing appendectomy during periods of selective (I, n = 153) and routine (II, n = 159) antibiotic use were compared. Although the rates of misdiagnosis were comparable (9% vs 13%), significantly more patients with appendicitis in Period II had perforated appendicitis (29 of 139 vs 44 of 139, P less than 0.05). Prophylactic antibiotics were given to 43 (28%) patients in Period I compared to 132 (83%) in Period II (P less than 0.001). This, increased frequency was true for both simple (21% vs 81%, P less than 0.001) and perforated (66% vs 86%, P less than 0.05) appendicitis. A single antibiotic, most frequently a cephalosporin, was used significantly more often in Period II (44% vs 82%, P less than 0.001). There was no significant difference in the methods of wound closure between the two periods. The incidence of infectious complications was similar in patients with simple appendicitis in both periods (8% vs 11%), but it was significantly greater during Period I in patients with perforated appendicitis (45% vs 20%, P less than 0.05). The overall infection rate was similar in both periods (16% vs 22%). Thus, high-risk patients with perforated appendicitis were more likely to receive antibiotics and had a lower infection rate with routine antibiotic use. Furthermore, there was no overall change in the infection rate during this period, despite the use of less toxic, single drug regimens and a greater percentage of perforated appendicitis.

Acute Disease↗
PubMed1992

The long-term effect of jejunoileal autotransplantation on intestinal function.

Disturbed intestinal absorption has been demonstrated almost uniformly early after intestinal autotransplantation. Our aim was to study the long-term effects of autotransplantation on intestinal absorptive function. Studies of nutritional status and absorptive function were performed on groups of dogs at three intervals after autotransplantation: I (less than 6 months; n = 4), II (6 to 12 months; n = 4), and III (12 to 18 months; n = 4). At death samples of intestinal fluid were obtained for bacteriologic analysis, and studies of morphology and in vitro absorption were performed on intact and autotransplanted intestine. Similar studies were performed on a group of five control animals. Although body weight and serum albumin levels remained stable in dogs that had undergone autotransplantation and initial diarrhea improved, stool moisture was persistently elevated and late defects in fat and D-xylose absorption developed (4.8% +/- 3.2% stool fat at 12 months vs 2.1% +/- 0.6% before surgery and 3.4 +/- 2.0 x 10(-2) mmol/L xylose/hr at 12 months vs 8.8 +/- 5.4 x 10(-2) mmol/L xylose/hr before surgery; p less than 0.05). In vitro glucose uptake and villus height were similar in autotransplanted and adjacent intact intestine at death. Compared with control animals, animals that had undergone autotransplantation demonstrated significant overgrowth of fecal flora in jejunum and ileum (14/18 segments greater than 10(5) bacteria vs 6/15 segments; p less than 0.05). Thus delayed defects in intestinal absorption of fat and D-xylose occurred more than 12 months after autotransplantation. Because intestinal structure and function of the autotransplanted intestine were similar to those of adjacent intact intestine, this malabsorption may be related to bacterial overgrowth or other in vivo factors.

Animals↗
PubMed1991

Reduction of the active-site iron by potent inhibitors of lipoxygenases.

Lipoxygenases are non-heme iron dioxygenases that catalyze the oxygenation of polyunsaturated fatty acids. Using soybean lipoxygenase-1 as a model, we have shown that two classes of lipoxygenase inhibitors currently in development as potential antiinflammatory agents obtain a significant amount of their potency by reducing the lipoxygenase active-site iron from the active ferric state to the inactive ferrous state. It is not surprising that the members of the first of these classes, the 2-benzyl-1-naphthols, are reducing agents. The members of the second class, the N-alkyl-hydroxamic acids, were not anticipated to be sufficiently strong reducing agents to be oxidized by the lipoxygenase ferric center; that they are provides additional evidence for that iron having a high reduction potential. This brings to (at least) five the number of classes of lipoxygenase inhibitors that are capable of reducing the active-site ferric ion and suggests the generality of this approach in the rational design of lipoxygenase inhibitors.

Binding Sites↗
PubMed1991

Factors affecting plasma postheparin diamine oxidase activity.

Plasma postheparin diamine oxidase (DAO) activity has been evaluated for assessing disease activity in Crohn's disease (CD) and other intestinal disorders. Since the mechanism of the reduced plasma DAO activity is poorly understood, our aim was to determine the effect of extent and location of disease and prior resection and therapy on plasma DAO activity in Crohn's disease. Plasma postheparin DAO activity was significantly lower (17.4 +/- 3.0 vs 32.8 +/- 30.8 units/ml) and Crohn's disease activity index (178 +/- 105 vs 14 +/- 19, P less than 0.05) (CDAI) higher in 37 patients with CD compared to 30 normal volunteers. There was no overall correlation between DAO activity and CDAI. Effective medical or surgical therapy increased DAO activity and decreased CDAI, while clinical recurrence had the opposite effect. DAO activity was not related to the extent of small bowel disease (13.2 +/- 9.1; less than 30 cm, 18.5 +/- 11.8; 30-60 cm, and 5.7 +/- 6.4 units/ml; greater than 60 cm) or colonic disease (13.0 +/- 6.9 segmental vs 24.0 +/- 15.4 units/ml, pancolitis). DAO activity was similar with small or large bowel disease (14.3 +/- 10.6 vs 18.8 +/- 13.1 units/ml). Prior enterectomy or colectomy did not significantly influence DAO activity. DAO activity responds predictably after effective therapy and recurrence and may prove useful in monitoring individual patients with CD. Failure of extent and location of disease and prior resection to influence DAO activity suggests that DAO activity is not directly related to enterocyte mass.

Adult↗
PubMed1991

Influence of the etiology of pancreatitis on the natural history of pancreatic pseudocysts.

We reviewed our experience with 90 patients with pancreatic pseudocysts to determine if the cause of pancreatitis influenced the patients' outcome. Acute pancreatitis (AP) occurred in 57 (63%) patients due to alcoholic (n = 15), postoperative (n = 14), biliary (n = 12), and other etiologies (n = 16). Thirty-three (37%) patients had chronic pancreatitis (CP) secondary to alcohol use (n = 27) or other causes (n = 6). Multiple pseudocysts were significantly more frequent in patients with acute alcoholic pancreatitis than in patients with chronic pancreatitis (47% versus 19%, p < 0.05). Spontaneous resolution occurred within 8 weeks in 10 (11%) patients with pseudocysts (AP = 9%, CP = 15%, p = NS). However, no patient with pseudocyst associated with biliary or postoperative pancreatitis underwent spontaneous resolution. Although pseudocysts associated with chronic pancreatitis were smaller in size (8.0 +/- 4.7 versus 5.7 +/- 3.8 cm, p < 0.05), a similar proportion of them required operation compared with AP pseudocysts (56% versus 58%). There were significantly more deaths in patients with postoperative pancreatitis compared with all other groups (29% versus 7%, p < 0.05). The outcome of pseudocysts was similar regardless of size (greater than 6 cm versus less than 6 cm) and presentation (acute versus delayed). Thus, the etiology of pancreatitis was a more important determinant of pseudocyst outcome than pseudocyst size or presentation.

Acute Disease↗
PubMed1991

Experience with intestinal lengthening for the short-bowel syndrome.

Patients with the short-bowel syndrome frequently develop dilated intestinal segments that may lead to impaired motility and malabsorption. Although intestinal tapering alone improves motility, the intestine can be lengthened as well. We reviewed our experience with six children undergoing intestinal lengthening to improve intestinal absorption secondary to the short-bowel syndrome. The procedure was performed by dissecting the vessels along the mesenteric border and dividing the intestine longitudinally with a stapler. Five patients were receiving total parenteral nutrition (TPN) and one was becoming malnourished with enteral feedings alone. Bacterial overgrowth was documented in four patients and abnormal liver function in three patients. The intestinal segments were dilated up to 10 cm in diameter and remnant length ranged from 15 to 79 cm. Segments 5 to 25 cm in length were divided, resulting in an average increase in length of 52%. Necrosis of one of the divided limbs necessitated resection in one patient. Follow-up ranged from 2 to 84 months. TPN has been discontinued in four patients and avoided in another. Symptomatic improvement occurred in all patients. We feel the tapering and lengthening procedure should be considered in patients with symptomatic, dilated intestinal segments in whom the need for TPN may potentially be obviated.

Anastomosis, Surgical↗
PubMed1991

The effect of intestinal autotransplantation on serum diamine oxidase activity.

Circulating levels of diamine oxidase (DAO), a mucosal enzyme found primarily in the small intestine, have been shown to reflect intestinal mucosal damage in a variety of disease states. Our aim was to assess the usefulness of both basal and postheparin DAO activity as a marker of intestinal allograft rejection by studying the influence of the nonrejection effects of intestinal transplantation on these activities. This separation of the immunological from all other effects of transplantation was achieved by studying 11 dogs who had undergone autotransplantation of the small intestine and 11 unoperated controls. Basal serum DAO activity increased during the first 3 postoperative days following autotransplantation (20.5 +/- 0.7 units/ml on Day 3 versus 6.9 +/- 4.1 units/ml preoperatively, P less than 0.05) but thereafter returned to control levels at 1 month and remained so for more than 18 months. Postheparin DAO activity was similar in both groups with a maximum increase between 15 and 60 min following heparin administration. There was no correlation between maximal DAO activity and time since operation in the transplant group. Intestinal DAO activity was similar to unoperated animals 18 months after autotransplantation. These findings suggest that postheparin serum diamine oxidase activity is not influenced by autotransplantation and thus, is a potential marker of graft rejection following intestinal allotransplantation.

Amine Oxidase (Copper-Containing)↗
PubMed1991

Intestinal diamine oxidase levels reflect ischemic injury.

Mucosal diamine oxidase (DAO) decreases during intestinal ischemia and may be a useful marker of intestinal ischemic injury. Tissue DAO activity and histologic changes were studied in intestinal segments taken from the midpoint of the small intestine before and 2, 4, and 24 hr after manipulation of the intestinal blood supply in 24 mongrel dogs. Intestinal DAO activity decreased significantly (17 +/- 21% of control value) 24 hr after SMA ligation and was associated with abnormal histology (histology score 7.8 +/- 2.9 at 24 hr vs 0.3 +/- 0.5 at 0 hr). SMA occlusion for 2 hr resulted in a significant decrease in DAO activity (45 +/- 36% of control value) 4 hr after manipulation which returned to normal at 24 hr, as did the histologic injury. Ligation of both the mesenteric arteries and veins resulted in a more rapid decrease in DAO activity. Decreased DAO activity correlated with the extent of histologic injury. Intestinal ischemia is associated with decreased intestinal DAO activity, which is influenced by the mechanism and duration of intestinal ischemia.

Amine Oxidase (Copper-Containing)↗