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Biomedical subjects

M C Regan

Publications and source records attributed to M C Regan.

At least 19 recordsLinked to original sources

Intravasation of barium sulphate at barium enema examination.

We report a case of venous intravasation of barium sulphate occurring during a routine barium enema examination for investigation of rectal bleeding. The patient suffered a cardiopulmonary arrest, but made a full recovery after organ support in intensive care. Review of radiographs from the examination showed intravasated barium in pelvic vessels. We review the literature on this rare, but serious, complication of barium enema examination and suggest measures by which intravasation can be prevented.

Aged↗

An unusual cause of biliary stricture in a patient with neurofibromatosis type 1.

The majority of biliary strictures occur as a consequence of iatrogenic injury to the extrahepatic biliary tract, with more than 80% following cholecystectomy. The laparoscopic era has led to heightened awareness of this problem. The occurrence of an iatrogenic stricture can be particularly devastating to both patient and surgeon. The literature highlights a number of factors involved in the aetiology of such traumatic stricture formation. We report an unusual case of a Bismuth 2 stricture of the proximal common hepatic duct,occurring in a patient with type 1 neurofibromatosis, following an iatrogenic bile duct injury that occurred during a laparoscopic cholecystectomy. Histological examination of the strictured region of bile duct removed at surgery demonstrated multiple neurofibromas of varying sizes present in the submucosa. Neurofibromatosis type 1 (von Recklinghausen disease) affects the gastrointestinal tract in up to 25% of cases, and in such cases is characterized by multiple submucosal neurofibromas. We believe this is the first reported case of a biliary stricture in a patient with neurofibromatosis type 1, which appeared to be as a consequence of neurofibromas in the submucosa of the bile duct.

Adult↗

Stricture formation in Crohn's disease: the role of intestinal fibroblasts.

OBJECTIVE: To determine whether intestinal fibroblasts in patients with Crohn's disease (CD) have an enhanced capacity to reorganize collagen and thus cause stricture formation. SUMMARY BACKGROUND DATA: Stricture formation is a characteristic feature of CD that may distinguish it from other forms of inflammatory bowel disease. Methods Fibroblasts were obtained at surgery from the colon and ileum of patients with CD and ulcerative colitis (UC) and control patients. Primary fibroblast cultures were obtained by explant technique. Fibroblast contractile activity was measured using fibroblast-populated collagen lattices (FPCLs), in which the cultured fibroblasts were seeded in free-floating collagen gel matrices that they reorganize and contract. Fibroblast contractile activity was measured as the reduction of surface area (mm2) of collagen gel matrix at 24-hour intervals for 1 week. RESULTS: Fibroblasts from patients with CD displayed enhanced capacity to contract FPCL when compared to UC and control fibroblasts. This activity was maximal in fibroblasts recovered from strictured regions in CD. Fibroblasts from patients with UC had a contractile capacity similar to that of controls. Hydrocortisone inhibited this in vitro contractile activity in a dose-dependent manner. CONCLUSIONS: Intestinal fibroblasts in CD possess enhanced capacity for collagen reorganization and contractile activity in vitro. This activity may be responsible for stricture formation in CD.

Cell Line↗

Mucosal metabolism in ulcerative colitis and Crohn's disease.

PURPOSE: Colonic mucosal metabolism of butyrate may be impaired in ulcerative colitis. In this study we sought to confirm this observation, to determine if a similar change occurs in Crohn's colitis, and to establish whether a panenteric disorder of butyrate metabolism exists in either condition. METHODS: With use of a microculture technique, mucosal metabolic fluxes of 14[C]-labeled butyrate and 14[C]-labeled glutamine were measured as 14[C] carbon dioxide production in mucosal biopsy specimens from the colon and ileum in patients with ulcerative colitis, Crohn's colitis, and healthy bowel. Results were expressed as pmol/microg biopsy DNA/hour. RESULTS: In the colon the mucosal metabolic fluxes of both butyrate and glutamine are reduced in both ulcerative colitis and Crohn's colitis compared with healthy controls. These changes were most marked in the presence of moderate to severe mucosal inflammation, there being no significant difference in mucosal metabolic flux between mildly inflamed mucosa and healthy controls. In the ileum the mucosal metabolic fluxes of butyrate and glutamine did not differ between healthy controls and those with either ulcerative colitis or Crohn's colitis. CONCLUSIONS: Changes in colonic mucosal metabolism of butyrate and glutamine in inflammatory bowel disease occur as a consequence of the inflammatory process and are not peculiar to ulcerative colitis. Ileal mucosal metabolism is unchanged in ulcerative colitis and Crohn's colitis, indicating the absence of a panenteric abnormality of mucosal metabolism in these two conditions.

Biopsy↗

Changes in regional renal blood flow after unilateral nephrectomy using the techniques of autoradiography and microautoradiography.

PURPOSE: To determine alterations in regional renal blood flow following unilateral nephrectomy using an autoradiographic technique. The role of prostaglandins and the sympathetic nervous system in the mediation of these changes was assessed. MATERIALS AND METHODS: C-14 iodoantipyrine was used as a tracer to measure intrarenal blood flow in anaesthetised rats at multiple time points following nephrectomy. Autoradiographs were produced from tissue sections. C-14 concentrations were measured from standards thus allowing blood flow values to be calculated. RESULTS: Base line values for cortical and medullary blood flow were 806 +/- 63 and 373 +/- 39 ml./100 gm./min. (mean +/- SEM) respectively. At 2 hours post nephrectomy blood flow to both the cortex and medulla increased significantly (1152 +/- 54 and 594 +/- 37; p < 0.05). Blood flow had returned to control levels by 24 hours and was maintained at 5 days post-nephrectomy. Multiple discrete regions of high blood flow within the cortex were observed. Microautoradiography defined the morphological location of these discrete regions of higher blood flow as periglomerular vasculature. Diclofenac administration did not inhibit the augmentation in cortical blood flow post-nephrectomy, while medullary blood flow fell below base line values at both 30 minutes and 2 hours following nephrectomy. Sympathetic denervation did not affect the changes in cortical blood flow seen following nephrectomy, but did ameliorate the changes in medullary blood flow. CONCLUSIONS: Significant, transient changes in regional renal blood flow occur in the residual kidney following unilateral nephrectomy. The interaction between vasoactive mediators and the autonomic nervous system which produces changes in cortical blood flow is complex. It is evident, however, that medullary blood flow is dependent on local prostaglandin production and is also influenced by sympathetic nervous supply.

Animals↗

Metabolic substrate utilization differs in ileal faecal and urinary reservoirs.

BACKGROUND: Construction of an ileal faecal or urinary reservoir profoundly alters ileal luminal ecology and availability of mucosal metabolic substrates. The aims of this study were to measure mucosal metabolic flux of butyrate and glutamine in histologically normal (control) ileum and to determine the effect of reservoir construction on metabolic fluxes in patients with ileal pouch-anal anastomosis and ileocystoplasty. METHODS: Endoscopic biopsy samples were obtained from normal ileum (n = 10), ileum of patients with ulcerative colitis (n = 10), ileal pouch-anal anastomosis (n = 7), ileocystoplasty (n = 7) and ileal conduit (n = 7). Using a closed microculture technique, biopsy utilization of 14C-labelled butyrate and glutamine was measured as [14C]carbon dioxide production. Biopsy DNA content was measured and [14C]carbon dioxide evolution expressed as picomoles [14C]carbon dioxide per microgram DNA per hour. RESULTS: The metabolic flux of both butyrate and glutamine was reduced in ileal pouch mucosa compared with that of ileal mucosa in patients with ulcerative colitis. In contrast, the metabolic flux of buyrate alone was reduced in ileal mucosa from ileocystoplasty and ileal conduit compared with that in normal ileal mucosa, while the metabolic flux of glutamine remained unchanged. CONCLUSION: Ileal mucosal metabolic fluxes measured in vitro are altered by changing luminal ecology in vivo. These changes may affect the health and mucosal integrity of ileum used to construct these reservoirs.

Butyrates↗

Diphenylhydantoin sodium promotes early and marked angiogenesis and results in increased collagen deposition and tensile strength in healing wounds.

BACKGROUND: Sodium diphenylhydantoin (DpH) (phenytoin) was first introduced as an antiepileptic in 1938. One of its side effects, gingival hyperplasia, prompted investigation into the possible application of this drug as a promoter of wound healing. Since the late 1950s phenytoin has been used in a variety of clinical situations. However, its exact mechanism of action is still debated. The aim of this study was to determine the effect of DpH on wound healing in an incisional rat model. METHODS: A four dorsal wound model was used, and each cephalad wound had a polyvinyl alcohol sponge placed in a subcutaneous pocket just above its cephalad end. Caudal and cephalad wounds were treated with 10 mg DpH in 200 microliters carrier, and the other two wounds received an equal volume of the saline vehicle as controls on the day of wounding and on the third and sixth postoperative days. The animals were killed on the tenth postwounding day. Tensile strength of fresh and fixed scars was determined using constant speed tensiometry, and wound hydroxyproline was determined spectophotometrically. RESULTS: There was a highly significant increase in both fresh and fixed wound tensile strength of all DpH-treated wounds compared with controls (p < 0.001). This was reflected by a significant increase in polyvinyl alcohol sponge hydroxyproline in DpH-treated wounds compared with saline-treated wounds (p = 0.002). Histologic examination of these wounds was performed at 3 and 6 days after wounding. There was moderate fibroblast infiltration with a marked inflammatory infiltrate and neovascularization in the DpH-treated wounds compared with controls at 3 days. By day 6, the inflammatory infiltrate had almost totally receded in the treated wounds, but fibroblast infiltration and angiogenesis were still persistently marked. In comparison, the saline-treated wounds still had moderate inflammatory and fibroblast infiltrate and mild angiogenesis. CONCLUSIONS: DpH alters the natural course of wound healing and may be of benefit in clinical situations where defective wound collagen deposition may lead to poor wound healing and consequent morbidity and mortality.

Animals↗

Determination of testicular function after torsion by DNA flow cytometry of serial fine-needle aspirates.

OBJECTIVE: To determine the efficacy of DNA flow cytometric analysis of testicular percutaneous fine-needle aspirates in the assessment and follow-up of testicular function after torsion, and to determine the relationship between the duration of torsion and testicular injury. MATERIALS AND METHODS: Three groups of 15 adult rats underwent a 720 degrees torsion, with fixation of the mesorchial ligament, for 1, 3 or 5 h. Bilateral aspirations, performed 7, 21 and 35 days after torsion were examined by flow cytometry. Testes were harvested and evaluated histologically using Johnsen's scoring. RESULTS: Irreversible testicular injury occurred in all three groups of rats, with loss of function after 1 h and loss of viability after 3 and 5 h. The results from flow cytometry suggested significant contralateral testicular injury (P < 0.025) but this was not supported by the histological evaluation. There was a strong correlation between the testicular function assessed by flow cytometry and by Johnsen's scoring of histological specimens (r2 = 0.95). CONCLUSION: The assessment of testicular aspirates by flow cytometry allows testicular function to be followed after torsion in rats, and potentially in humans. Using DNA flow cytometry, the temporal course of the twisted testis in the adult rat was determined; contralateral testicular injury following the reversal of torsion could not be excluded.

Animals↗

Methods of renal blood flow measurement.

Variations in regional renal blood flow have been implicated in a variety of disease states. Many techniques have been developed in an attempt to accurately assess these changes. The microsphere technique is the most widely used method at the present time. This technique allows focal measurements to be performed, but there is a conflict between the resolution of the method and the number of microspheres necessary in each sample. New imaging techniques such as tomography and autoradiography enable visual assessment of renal blood flow. Though there is no ideal method, these techniques have opened up new possibilities in the quantification of regional renal blood flow.

Autoradiography↗

Cardiorespiratory effects of laparoscopy with and without gas insufflation.

BACKGROUND: Patients who are undergoing laparoscopic procedures can present with a number of ventilatory and circulatory problems. The use of a gasless technique for performing a laparoscopy by using a mechanical lifting device may potentially avoid such problems. OBJECTIVE: To compare the cardiorespiratory effects of laparoscopy with and without gas insufflation. METHODS: Twelve adult pigs were randomized to undergo a laparoscopy by using either carbon dioxide insufflation or mechanical elevation. Full invasive monitoring was performed preoperatively and at 10-minute intervals throughout the operative period. Parameters that were measured included blood gas determinations, mean arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac output, stroke volume, and total peripheral resistance. RESULTS: Carbon dioxide insufflation unlike mechanical elevation led to a fall in PO2 and absorption of a significant quantity of CO2, resulting in hypercapnia, acidosis, and a consequent hyperdynamic circulation. CONCLUSION: These findings have significant implications for the use of CO2 insufflation for laparoscopy in patients with a compromised respiratory or cardiac status.

Animals↗

Regional renal blood flow in normal and disease states.

Renal function is intimately dependent on renal blood flow. Alterations in either total or regional renal blood flow have major consequences for renal function. Through homeostatic mechanisms the kidneys are able to maintain relatively stable rates of flow over a wide range of perfusion pressures. A combination of neural, endocrine, exocrine and autocrine signals serve to regulate renal blood flow at both local and systemic levels. Alterations in the balance of these systems occur in the presence of certain pathophysiological conditions and an understanding of the subsequent changes in regional renal blood flow distribution aids in the understanding of the associated changes in renal function. The regulation and distribution of regional blood flow and the effects of surgical and pathophysiological conditions on these factors are reviewed.

Diabetes Mellitus↗

Superoxide radical and xanthine oxidoreductase activity in the human heart during cardiac operations.

BACKGROUND: The results of clinical trials of xanthine oxidoreductase inhibition in cardiac surgery are encouraging, although studies have failed to localize the enzyme to the human heart and to localize free radical activity to fresh human heart. METHODS: We adapted a histochemical staining technique based on the reduction of nitro blue tetrazolium to formazan by superoxide radical. In six samples of right atrium graded blindly on a scale of 0 through 4, strong staining (median grade, 3) of the microvasculature was seen. This was blocked by allopurinol in paired sections (median grade, 1; p < 0.01). Chemiluminescence can be used as an index of superoxide radical activity. Atrial samples were taken from 13 patients at five time points during coronary bypass grafting and placed in buffered luminol. Then chemiluminescence was measured. RESULTS: A 15-fold rise in chemiluminescence (295.93 +/- 39.47 mV) was demonstrated during reperfusion compared with the control value (19.06 +/- 0.47 mV). Chemiluminescence at 1 minute after release of the cross-clamp was significantly higher (p < 0.05) by analysis of variance versus values obtained before bypass and 1 minute before and 30 minutes after reperfusion. CONCLUSIONS: In this study we have identified superoxide radical activity and a possible generating system (xanthine oxidoreductase) in the human heart.

Aged↗

Immune involvement in wound healing.

Both in vitro and in vivo studies have demonstrated that the presence of both macrophages and T lymphocytes at the wound site is essential in order for the normal healing process to occur. Both macrophages and T lymphocytes possess the capacity to regulate essential steps in the process of wound healing. The presence of macrophages is essential for the initiation and maintenance of wound fibroblast activity. T cells do not appear to be required for the initiation of the healing process, and healing can progress in the absence of T lymphocytes, but the presence of an intact T-cell immune system is essential for a normal outcome, indicating that the T cells probably exert a regulatory influence over macrophage-induced activities. Further research is still required into the interaction of these immune cells, their secretory products, and other wound elements before our understanding of the mechanism of wound healing is complete.

Animals↗

Postoperative immunological function and jaundice.

The effects of operative trauma and obstructive jaundice on systemic immunity were studied in a rat model, using the delayed-type hypersensitivity response to 2,4-dinitro-1-fluorobenzene as a measure of systemic immune responsiveness. Midline laparotomy caused a significant decrease in the mean(s.e.m.) delayed-type hypersensitivity response 1 week after operation (4.6(1.3) versus 19.0(2.2) per cent for controls). The response returned to control levels by 2 weeks (14.6(3.1) per cent). Common bile duct ligation and division resulted in a significantly depressed hypersensitivity response at 2 and 3 weeks (6.8(2.0) and 8.4(1.6) per cent respectively). The expected decrease in the response at 1 week in these animals was not observed (mean(s.e.m.) 12.7(2.7) per cent), suggesting a possible role for the normal liver in the induction of postoperative immune depression. Impaired function of the reticuloendothelial system was induced in non-jaundiced animals by Kupffer cell ablation following intraportal infusion of lambda-carrageenan. A similar prevention of postoperative immune hyporesponsiveness was observed (mean(s.e.m.) 10.4(1.0) versus 10.4(1.6) per cent for controls). Hepatic Kupffer cells play an important role in the induction of postoperative immune depression.

Animals↗

Sepsis impairs gut amino acid absorption.

Sepsis has been shown to adversely affect the barrier and metabolic functions of the small intestine as well as to reduce mesenteric blood flow and cause histologic damage. However, the effect of sepsis on gut absorptive function has been largely ignored. In this study, intestinal absorption of arginine and an amino acid analogue, aminoisobutyric acid, was studied using in vivo and in vitro techniques in an experimental model of sepsis. In vivo studies showed a significant impairment in the absorption of both amino acids from the intestinal lumen 24 and 72 hours after cecal ligation and puncture. Uptake of these amino acids by everted gut sacs prepared from septic animals was also significantly reduced. This reduction in absorptive capacity of the gut may limit the ability of enteral feeding alone to supply nutritional requirements during sepsis and may also contribute to the associated morbidity and mortality.

Aminoisobutyric Acids↗

Arginine stimulates wound healing and immune function in elderly human beings.

BACKGROUND: Experimentally, arginine enhances immune function and promotes wound healing. In this randomized double-blind study we investigated the effect of oral arginine supplementation on wound healing and T-cell function in elderly human beings (more than 65 years of age). METHODS: Thirty elderly, healthy, human volunteers (15 men and 15 women) received daily supplements of 30 gm arginine aspartate (17 gm free arginine). Fifteen volunteers (nine men and six women) received a placebo syrup. Fibroplastic wound responses were assessed by inserting a polytetrafluoroethylene catheter subcutaneously into the right deltoid region. Epithelialization was examined by creating a 2 x 2 cm split thickness wound on the lateral aspect of the upper thigh. Mitogenic response of peripheral blood lymphocytes to concanavalin A, phytohemagglutinin, pokeweed mitogen, and allogeneic stimuli was assayed at the beginning and end of supplementation. Polytetrafluoroethylene catheters were analyzed for alpha-amino nitrogen (assessment of total protein accumulation), hydroxyproline (index of reparative collagen synthesis), and DNA accumulation (index of cellular infiltration). RESULTS: Arginine supplementation for 2 weeks significantly enhanced wound catheter hydroxyproline accumulation (26.49 +/- 2.39 nmol/cm vs 17.41 +/- 2.04 nmol/cm) and total protein content (43.47 +/- 3.85 micrograms/cm vs 21.95 +/- 2.5 micrograms/cm). Arginine did not influence the DNA content of the catheters or the rate of epithelialization of the skin defect. Peripheral blood lymphocyte responses to mitogenic and allogenic stimulation were greater in the arginine supplemented group. Serum insulin-like growth factor-1 levels were significantly elevated in the arginine group. CONCLUSIONS: The data suggest that arginine supplementation may improve wound healing and immune responses in the elderly.

Aged↗