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Biomedical subjects

J S Thompson

Publications and source records attributed to J S Thompson.

At least 37 records · Page 2Linked to original sources
PubMed2000

The NADPH oxidase inhibitors iodonium diphenyl and cadmium sulphate inhibit hypoxic pulmonary vasoconstriction in isolated rat pulmonary arteries.

Interest surrounds the role of an NADPH oxidase-like enzyme in hypoxic pulmonary vasoconstriction (HPV). We have studied the effects of the NADPH oxidase inhibitors iodonium diphenyl (ID) and cadmium sulphate (CdSO4) upon HPV of isolated rat pulmonary arteries (n = 73, internal diameter 545 +/- 23 microm). Vessels were preconstricted with prostaglandin F2alpha (PGF2alpha, 0.5 or 5 microM) prior to a hypoxic challenge. ID (10 or 50 microM), CdSO4 (100 microM) or vehicle (50 microl) was added for 30 min before re-exposure to PGF2alpha and hypoxia. ID and CdSO4 significantly inhibited HPV. In vessels preconstricted with 5 microM PGF2alpha, ID (10 and 50 microM) reduced HPV from 37.4 +/- 5.6 % to 9.67 +/- 4.4 % of the contractile response elicited by 80 mM KCl (P<0.05) and from 30.1 +/- 5.0 % to 0.63 +/- 0.6% 80 mM KCl response (P<0.01), respectively. CdSO4 (100 microM) reduced HPV from 29.4 +/-4.0 % to 17.1 +/- 2.2% 80 mM KCl response (P<0.05). In vessels preconstricted with 0.5 microM PGF2alpha, ID (10 and 50 microM) reduced HPV from 16.0 +/- 3.15% to 3.36 +/- 1.44 % 80 mM KCl response (P<0.01) and from 15.0 +/- 1.67 % to 2.82 +/- 1.40 % 80 mM KCl response (P<0.001), respectively. Constriction to PGF2alpha was potentiated by ID. ID and CdSO4, at concentrations previously shown to inhibit neutrophil NADPH oxidase, attenuate HPV in isolated rat pulmonary arteries. This suggests that an NADPH oxidase-like enzyme is involved in HPV and could act as the pulmonary oxygen sensor.

Animals↗
PubMed1999

Surgical approaches to improving intestinal function in the short-bowel syndrome.

HYPOTHESIS: Nontransplantation surgical approaches to improve intestinal function in patients with the short-bowel syndrome have a satisfactory outcome in selected patients. PATIENTS: Ninety adult (aged >18 years) patients with intestinal remnants shorter than 180 cm were evaluated between 1980 and 1998. MAIN OUTCOME MEASURES: Clinical improvement (reduction in parenteral nutrition, resolution of anatomical problems, decreased symptoms, or improved oral intake) and postoperative morbidity and mortality rates. RESULTS: There were 17 deaths within 30 days after resection. Thirty-seven (51%) of the surviving 73 patients underwent 43 procedures to improve intestinal function. Fourteen procedures (33%) were intended to expand intestinal surface area by restoring intestinal continuity (n = 10), recruiting additional length (n = 3), or longitudinal lengthening (n = 1). Twenty-six procedures (60%) aimed to alter intestinal function, either by relieving obstruction (n = 10), repairing fistulas (n = 8), slowing transit (n = 4), eliminating diseased bowel (n = 3), or improving motility (n = 1). Three patients had stomas created to improve oral intake and relieve perianal symptoms. Postoperatively, 2 anastomoses leaked, 2 fistulas recurred, and there was 1 death (mortality, 2%). Thirty-seven procedures (86%) resulted in clinical improvement. Eleven (46%) of the 24 patients receiving parenteral nutrition were able to discontinue it and 5 patients were able to reduce the amount of parenteral nutrition received. Twelve procedures that increased surface area (86%) and 22 procedures that addressed functional problems (85%) resulted in clinical improvement. Success was lowest (50%) in patients having procedures to prolong transit time. CONCLUSIONS: Various nontransplantation surgical procedures have a role in improving intestinal function in short-bowel syndrome. These procedures usually result in clinical improvement in properly selected patients. Success is lowest for procedures designed to prolong intestinal transit time; thus, these procedures should be used only in carefully selected patients.

Adolescent↗
PubMed1999

Epidermal growth factor inhibits somatostatin-induced apoptosis.

BACKGROUND: The somatostatin analogue octreotide impairs intestinal regeneration and the adaptive response to intestinal resection by inhibition of enterocyte migration and proliferation and increased apoptosis. Epidermal growth factor (EGF) stimulates regeneration and adaptation by increasing proliferation and reducing apoptosis. The aim of this study was to determine the effect of EGF on octreotide-induced enterocyte apoptosis. METHODS: Twenty-four rabbits underwent patch enteroplasty in the distal ileum to stimulate the mucosa. There were four study groups: octreotide 250 microgram/kg/day, EGF 40 microgram/kg/day, EGF plus octreotide, and control. Normal ileal mucosa adjacent to the patch was evaluated at 7 days for villus height, crypt depth, crypt cell production rate (CCPR), and in situ end labeling of DNA fragmentation. RESULTS: Octreotide alone increased apoptosis compared with controls at the villus tip (40 +/- 7% vs 18 +/- 7%, P < 0.05), lateral villus (9 +/- 2% vs 3 +/- 2%, P < 0.05), and crypt (15 +/- 3% vs 10 +/- 3%, P < 0. 05). EGF decreased apoptosis in the crypt (2 +/- 1%) and villus (6 +/- 1% villus tip and 1 +/- 1% lateral villus, P < 0.05) compartments. EGF inhibited octreotide-induced apoptosis in the crypt (5 +/- 2%) but not the villus (31 +/- 5% villus tip and 6 +/- 2% lateral villus, P < 0.05). Mean DNA fragmentation was significantly greater in octreotide-treated animals (P < 0.05). The octreotide-treated animals had reduced crypt depth and villus height but normal CCPR compared with controls. EGF increased CCPR and crypt depth compared with controls. Combining EGF and octreotide resulted in crypt depth and CCPR similar to those of controls but reduced villus height. CONCLUSIONS: EGF inhibits octreotide-induced apoptosis. This effect is greater in crypt than in villus enterocytes. Octreotide appears to have both direct and indirect effects on enterocyte apoptosis.

Animals↗
PubMed1999

Comparison of ileal and jejunal transplantation after 50% proximal intestinal resection.

BACKGROUND: The ileum has a greater adaptive capacity than the jejunum after intestinal resection. Transposition studies suggest that this is, in part, related to increased exposure to nutrients. However, there may be regional differences in intestinal properties that contribute to this response as well. The aim of this study was to compare the outcome of replacing the jejunum with either ileal or jejunal transplants while preserving an intact ileum after 50% proximal resection. METHODS: Twenty-one Lewis rats were included in the study. One group (n = 7) served as transection controls (TC). The other two groups (n = 7) had 50% proximal resection with syngeneic transplantation of a similar length of ileum (ITX) or jejunum (JTX). Nutritional status and adaptation were studied at 14 days. RESULTS: JTX animals gained less weight than TC and ITX (104 +/- 2% vs 114 +/- 1 and 108 +/- 2% initial, P < 0.05). ITX and JTX groups had lower caloric intake and serum albumin levels compared with TC (7.4 +/- 0.4 and 7.2 +/- 0.8% vs 8.8 +/- 0.2% body weight and 2.6 +/- 0.1 and 2.4 +/- 0.9 g/dl vs 3.0 +/- 0.1 g/dl, P < 0.05). Mucosal thickness increased significantly in the ileal remnant of both ITX and JTX groups (9.2 +/- 2.1 and 8.8 +/- 0.6 micrometer vs 6.6 +/- 0.6 micrometer, P < 0.05). Transplanted ileum had mucosal thickness similar to that of jejunum. CONCLUSIONS: Transplanted ileum achieves an intestinal structure similar to that of the jejunum in the same environment. Modest adaptation of the remnant occurs with transplantation. Replacing jejunum with ileum rather than jejunum resulted in better weight gain, suggesting that intrinsic absorptive, motor, or hormonal rather than structural differences are responsible.

Animals↗
PubMed1999

Factors affecting outcome following proximal and distal intestinal resection in the dog: an examination of the relative roles of mucosal adaptation, motility, luminal factors, and enteric peptides.

In the clinical setting, resection of the ileum results in an inferior functional outcome compared to jejunal resection. This may be related to a greater adaptive capacity of the ileum, intrinsic structural and functional differences, or regional differences in motor and hormonal function. Our aim was to evaluate the relative contributions of these factors to functional outcome after resection of the proximal or distal intestine. Twenty-four dogs underwent either intestinal transection or 50% resection of the proximal or distal intestine. Studies (nutritional status, absorption, adaptation, motility, peptide levels) were performed every four weeks until the animals were killed at 12 weeks. Caloric intake was similar in all four groups. Weight loss was greater and more sustained after distal resection (DR). Serum cholesterol levels decreased significantly only in the DR group. While stool weight and moisture were similar, the DR animals had persistent, significant steatorrhea. Intraluminal anaerobic bacteria and SCFA concentrations were significantly greater in the ileum but were not influenced by resection. Intestinal remnant length increased to a greater extent after proximal resection (PR), but circumference increased to a similar extent after both resections. Villus height and crypt depth increased significantly only after PR. MMC frequency was similar in all four groups. In the DR animals 26% of migrating motor complexes (MMCs) originated within the remnant. The jejunal remnant of these animals had a dominance of cluster activity similar to the intact distal ileum. Following PR, the postprandial motilin response was decreased. After DR, there were transient increases in neurotensin and PYY. Of the various factors evaluated, mucosal adaptation and the intestinal motor response appear most likely to explain the inferior nutritional and absorptive outcome associated with resection of the distal small intestine.

Adaptation, Physiological↗
PubMed1999

Surgical approach to the short-bowel syndrome: procedures to slow intestinal transit.

Procedures designed to slow intestinal transit should be applied cautiously in patients with near adequate remnant length and demonstrated rapid transit. They should be considered after maximum adaptation has occurred. A reversed intestinal segment appears to be efficacious in the short term. Colon interposition and intestinal valves might also have merit in selected patients but clinical experience is limited. Unfortunately, these procedures are applicable to only a small proportion of patients with SBS.

Anastomosis, Surgical↗
PubMed1999

Intestinal transplantation. Experience in the United States.

This review presents recent experience with intestinal transplantation in the United States and Canada. Indications are for combined liver and small intestinal transplantation irreversible intestinal failure and end-stage liver disease, and--for isolated intestinal transplantation--intestinal failure associated with severe progressive complications of parenteral nutrition. With a proportion of 80%, short-bowel syndrome represents the major disease complex thus treated. Long-term graft and patient survival exceeds 50% in large series with better outcome for isolated intestinal grafts than for combined liver and small-bowel transplants. Limiting factors are infections (responsible for 60% of graft losses), frequently due to CMV or EBV, technical and management errors (22%), and rejection (14%). One of the main problems of immunosuppression is post-transplant lymphoproliferative disease with an incidence of 20% which seems especially linked with EBV infections, OKT3 and steroids. The first line immunosuppressive agent nowadays used is tacrolimus. Trials with unmodified donor bone-marrow infusions to promote graft acceptance have not proved successful so far. Hopes for the future include increasing use of living related donors in order to overcome the shortage of donor organs, and continuing progress in immunosuppression.

Adult↗
PubMed1999

A high dose of ionizing radiation induces tissue-specific activation of nuclear factor-kappaB in vivo.

Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) is one of the important responses of cells to an external stress such as ionizing radiation. We studied radiation-induced NF-kappaB activation in vivo in male BALB/c mice. After the mice were exposed to 8.5 Gy total-body gamma irradiation, the spleen, mesenteric lymph nodes, thymus, liver, lung, colon, brain and bone marrow were harvested 1, 2.5, 5, 10 and 20 h postirradiation. NF-kappaB DNA-binding activity was analyzed in the nuclear protein extracts by a gel shift assay. When compared to the levels in untreated control mice, radiation induced activation of NF-kappaB in spleen, mesenteric lymph nodes and bone marrow but not in the other tissues examined. In contrast, an i.p. injection of a lethal dose (3 mg/kg) of lipopolysaccharide also increased activity of NF-kappaB in the liver and lung. The gel supershift assay with Nfkb1, Rela and/or Rel antibodies revealed that the specific molecular forms of NF-kappaB activated by radiation in the spleen were Nfkb1 homodimers and Nfkb1/Rela heterodimers. In mesenteric lymph nodes, the heterodimerized Rel/Rela NF-kappaB was also activated. In bone marrow, an NF-kappaB-like binding factor was induced that may be Nfkb1/Rela- and Rel/Rela-like heterodimers, but it exhibited a higher mobility than Nfkb1 homodimers. These results indicate that in vivo, ionizing radiation induces NF-kappaB activation that varies in both tissue distribution and moleoular composition.

Animals↗
PubMed1998

Inhibition of hypoxic pulmonary vasoconstriction in isolated rat pulmonary arteries by diphenyleneiodonium (DPI).

The NADPH oxidase inhibitor, diphenyleneiodonium (DPI), is known to selectively inhibit hypoxic pulmonary vasoconstriction (HPV) in isolated rat and rabbit lungs. We have investigated whether DPI has similar effects in rat pulmonary arteries in vitro. Vessels (n=38, internal diameters 327+/-41 microM) were mounted in an automated myograph and preconstricted with prostaglandin F2alpha (PGF2alpha, 5 microM) before an acute hypoxic challenge. The effects of DPI (10 microM), or the vehicle DMSO, were studied on the first contractile phase of HPV. DPI (10 microM) was found to significantly inhibit HPV; 1.83+/-0.42 mN/mm (pre-DPI) compared to 0.11+/-0.22 mN/mm (post-DPI,P<0.01). However, the vehicle DMSO (0.2%) also resulted in a reduction of HPV, although this was significantly different from inhibition via DPI (P<0.05), implying a DPI-sensitive component. The effects of DPI (0.1-300 microM) were also studied on the second contractile phase of HPV. DPI (300 microM) caused a significant reversal of 45% (0.50-0.27 mN/mm) compared to 9% reversal (0.38-0.35 mN/mm) seen with DMSO (P<0.0001). The fact that an inhibitor of NADPH oxidase, the enzyme responsible for producing reactive oxygen species from oxygen, attenuated the pulmonary vascular response to hypoxia, may indicate that this, or a similar, enzyme is involved in oxygen sensing.

Animals↗
PubMed1998

Ileoanal pouch function and release of peptide YY.

PURPOSE: This study evaluates peptide tyrosine-tyrosine (PYY), intestinal transit, fecal retention time, and anal sphincter manometry in colectomized patients with ileal pouch-anal anastomosis. METHODS: Plasma and pouch PYY, mouth-to-pouch transit time, fecal retention time, and anal canal pressures were studied in 27 patients with ileoanal pouches a mean of 50 (range, 3-84) months after loop ileostomy closure. RESULTS: Basal and peak postprandial plasma PYY were significantly reduced in patients with pouches compared with controls (P < 0.0001). Pouch PYY was decreased compared with control ileal PYY (P = 0.0003). No significant correlation was noted between intestinal transit and total integrated PYY response in patients with pouches (r=0.36; P=0.06). Fecal retention time was related to postprandial total integrated response of plasma PYY (r=0.43; P=0.02), mouth-to-pouch transit (r=0.87; P < 0.0001), and resting (r=0.44; P=0.02) and squeeze (r=0.62; P=0.0006) anal sphincter pressures. CONCLUSIONS: Colectomized ileoanal patients with pouches showed decreased plasma and pouch PYY compared with controls. Intestinal transit was not significantly related to PYY release. However, prolonged pouch fecal retention was associated with greater PYY release, mouth-to-pouch transit, and anal sphincter pressures.

Adolescent↗
PubMed1998

Surgical experience with implantable insulin pumps. Department of Veterans Affairs Implantable Insulin Pump Study Group.

BACKGROUND: A recent Veterans Affairs cooperative trial demonstrated that intensive insulin therapy via an implantable pump with intraperitoneal insulin delivery reduced glycemic variability and improved quality of life compared with multiple daily insulin injections. Our aim was to determine perioperative morbidity and assess long-term function of the implantable insulin pump. METHODS: Fifty-one adult patients with type 2 diabetes had infusion pumps placed over a 2-year period at seven VA Medical Centers as part of a randomized prospective study. RESULTS: All pumps were placed successfully. There were two (4%) perioperative complications. There were no wound complications. Duration of pump use ranged from 12 to 25 months (mean 20). Catheter obstruction (57%) and pump malfunction (25%) were the most common reasons for pump explantation. Catheter occlusions increased after 12 months. Catheter occlusion was treated by percutaneous rinse procedure in 75% and revisional procedures in 31% of patients. CONCLUSIONS: Implantable insulin pumps can be placed with minimal surgical morbidity. Attention to surgical detail and infusion protocol permits satisfactory long-term function. Pump/catheter complications increase with time but are usually resolvable by either operative or percutaneous manipulations.

Aged↗
PubMed1998

Qualitative changes in enteric flora and short-chain fatty acids after intestinal resection.

Our aim was to determine the effect of intestinal transection and resection on the prevalence of enteric flora and evaluate whether any such changes alter luminal SCFA and lactic acid content. Dogs underwent either 50% proximal (PR, N = 6) or distal (DR, N = 7) resection, distal resection with bypass of the ileocecal junction (DRBP, N = 9) or midpoint transection alone performed to serve as the appropriate control for luminal sampling for either proximal (PTC, N = 6) or distal (DTC, N = 7) resection. Studies were performed every four weeks for 12 weeks. Both jejunum and ileum had >10(5)/ml aerobic bacteria, most commonly E. coli. Streptococcal species were more common in the normal jejunum than ileum but were found in the ileal remnant after PR. Significant (>10(5)) anaerobic growth occurred infrequently in the jejunum, and DR did not increase anaerobic growth in jejunum unless DRBP was performed (93% vs 62% DR, 45% DTC, 20% normal jejunum, P < 0.05). Clostridium species increased significantly in the jejunal remnant after DRBP. Significant anaerobic growth occurred infrequently in normal ileum but increased after PR (89% vs 50% PTC, P < 0.05). Flora normally found in the jejunum tended to increase in the ileum after PR. Jejunal SCFA increased after DRBP (3126 +/- 577 microg/ml vs 1600 +/- 301 DTC, P < 0.05) but not DR (1791 +/- 321 microg/ml). Significant (>10(5)) anaerobic bacterial growth was associated with increased SCFA content (2717 +/- 381 vs 1029 +/- 170 microg/ml, P < 0.05) and the presence of lactic acid (30% vs 5%, P < 0.05), but there was no correlation between the presence of specific bacteria and SCFA and lactic acid. Following resection of the proximal small intestine, the intestinal remnant tends to assume the bacteriologic characteristics of the resected segment. Following a distal resection, the presence of an intact ICJ protects against the proliferation of a flora characteristic of the distal intestine; resection with bypass of the ICJ results in the appearance of coliforms in the jejunal remnant. These changes in enteric flora do not correlate with content of specific SCFA and lactic acid in the small intestine.

Animals↗
PubMed1998

Increased efficacy of sodium nitroprusside in middle cerebral arteries following acute subarachnoid hemorrhage: indications for its use after rupture.

Sodium nitroprusside (SNP) is commonly used for controlled systemic hypotension during aneurysm surgery after acute subarachnoid hemorrhage (SAH). Few experimental studies have assessed cerebrovascular responsiveness to SNP acutely after a representative SAH (i.e., following arterial rupture within the subarachnoid space). Instead, most studies have focused on delayed reactivity after slow injections of unpressurized blood throughout several days. In the authors' study, SAH was created by endovascular rupture in spontaneously breathing rats under urethane anesthesia without craniotomy. After 3 hours, proximal middle cerebral arteries (MCAs) were harvested and mounted as ring preparations in vitro. After preconstriction with 30 mM prostaglandin F2a, concentration-response curves were generated to express SNP's sequential relaxation of preconstricted tone. The effective concentration of SNP for 50% relaxation was significantly lower after SAH (p < 0.001) as compared with non-operated and sham-operated controls. There was also a significantly greater maximum percentage relaxation from preconstricted tone (p < 0.001) with SNP. The results of this study suggest that SNP is a potent and efficacious dilator of MCAs in the hours immediately after acute SAH.

Acute Disease↗