Necrotizing fasciitis: two cases in a single family.
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Adult↗
Biomedical subjects
S J Kirk
Publications and source records attributed to S J Kirk.
Manipulation of the L-arginine-nitric oxide pathway in experimental colitis.
The role of the L-arginine-nitric oxide pathway in the pathogenesis of colonic inflammation was assessed using L-arginine and its competitive analogue N omega-nitro-L-arginine methyl ester (L-NAME) in a rat model of colitis. In the first study oral L-arginine 2 per cent (control: 3.4 per cent L-glycine) was administered with and without L-NAME 100 mg/l. Orally administered L-arginine increased colonic inflammation (P = 0.004) and decreased thymic weight (P = 0.0007). Addition of L-NAME reduced the colonic inflammation and prevented loss of body-weight (P < 0.04). In the second study L-NAME was administered orally in concentrations of 100, 200 and 500 mg/l (control: no L-NAME). L-NAME 500 mg/l reduced colonic inflammation and increased thymic weight and body-weight (P < 0.01). Thymic weight and body-weight correlated positively with the concentration of L-NAME administered orally (rs > or = 0.3, P = 0.04). L-NAME l g/l was administered topically as an enema (control: suspension agent). Topical L-NAME reduced colonic inflammation and increased thymic weight (P < 0.05). These results suggest that the L-arginine-nitric oxide pathway mediates colonic inflammation in this model.
Administration, Oral↗
Endotoxaemia and cytokine production in experimental colitis.
Systemic endotoxaemia is a well recognized feature of inflammatory bowel disease but its pathogenic role remains uncertain. This study examined plasma endotoxin and cytokine concentrations and the acute-phase protein response in a hapten-induced model of experimental colitis. On days 2, 8 and 14 after induction of colitis with trinitrobenzenesulphonic acid in ethanol (TNBS-E), plasma endotoxin, immunoglobulin (Ig) G and IgM endotoxin-core antibody (EndoCAb), tumour necrosis factor (TNF), interleukin (IL) 6 and alpha 2-macroglobulin (alpha 2M) concentrations and colon macroscopic inflammation score were determined. At all time points there was significant colonic inflammation when compared with control values (P < 0.0001). Animals treated with TNBS-E had raised concentrations of endotoxin at all time points (P < 0.04). In TNBS-E-treated animals EndoCAb concentrations were reduced on day 2 (P < 0.0001) and later increased. There were increases in IL-6 and alpha 2M concentrations in TNBS-E-treated animals but no significant change in TNF concentrations. Endotoxin concentrations correlated with macroscopic inflammation score, IL-6 and alpha 2M concentrations. There was a less consistent correlation between EndoCAb concentrations and these parameters. These results suggest that endotoxin is a mediator of the systemic response in this model of experimental colitis.
Animals↗
Topical glutamine therapy in experimental inflammatory bowel disease.
This study investigated the effects of glutamine and steroid enemas on disease activity in an animal model of colitis. Colitis was induced in male Wistar rats by intracolonic instillation of 30 mg trinitrobenzenesulphonic acid in 50% ethanol (TNBS/E). Controls were given an isovolumetric bolus of normal saline. After 24 h, animals were randomised to receive enemas (1 mL twice daily) of prednisolone (200 mg/L), or L-glutamine (500 g/L) or the suspending agent (placebo). On day 8, the colon was weighed and the degree of inflammation assessed using a colon macroscopic score (CMS). Thymic weight, splenic weight, percentage gain in body weight (%GBW), food intake, plasma interleukin-6 (IL6) and plasma alpha(2)-macroglobulin (alpha(2)M) were also determined. There was a significant increase in CMS, colon weight, splenic weight, IL6 and alpha(2)M in TNBS/E animals compared to controls (P< 0.01). There was also a significant decrease in %GBW, food intake and thymic weight in TNBS/E animals (P< 0.01). The therapeutic enema of prednisolone reduced colonic inflammation (CMS, colon weight), improved thymic weight, %GBW and food intake, and reduced plasma IL6 concentrations (P< 0.05). In contrast administration of glutamine enemas was associated with an exaggerated acute phase protein (alpha(2)M) response (P< 0.05) and failed to improve the colonic and systemic inflammatory response in this experimental model of colitis.
Journal Article↗
Modulation of immune function and weight loss by L-arginine in obstructive jaundice in the rat.
Jaundiced surgical patients have a high incidence of postoperative complications. Many causative factors have been identified including cachexia and immune suppression. The amino acid L-arginine has anabolic and immunostimulatory properties. It was hypothesized that dietary supplementation with L-arginine would diminish the weight loss and immune suppression of obstructive jaundice. Sixteen male Wistar rats rendered jaundiced by bile duct ligation were allocated to two groups. The test group (n = 8) received drinking water supplemented with 1.8 percent L-arginine ad libitum and the control group (n = 8) received a solution of isonitrogenous glycine. Both groups had free access to standard chow. Body-weight, and fluid and food intake were recorded. After 21 days, delayed-type hypersensitivity to 2,4-dinitrofluorobenzene was assessed. Animals receiving L-arginine consumed more food than controls (mean(s.e.m.) 414(16) versus 360(13) g, P < 0.05) and lost less weight (mean(s.e.m.) proportion of initial body-weight lost 7.8(1.2) versus 14.8(1.4) percent, P < 0.05). The delayed-type hypersensitivity response was significantly greater in rats receiving L-arginine (mean(s.e.m.) increase in ear thickness 23.9(2.7) versus 9.4(2.1) percent, P < 0.05). In this animal model of obstructive jaundice dietary supplementation with L-arginine diminished both weight loss and immune suppression.
Animals↗
The L-arginine/nitric oxide pathway--biological properties and therapeutic applications.
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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↗
Tumor necrosis factor-alpha inhibits in vivo collagen synthesis.
In this study we sought to determine the in vivo role of tumor necrosis factor-alpha (TNF-alpha) at the wound-healing site. In vivo abrogation of endogenous TNF-alpha activity in experimental wounds by administration of anti-murine TNF-alpha rabbit serum resulted in a significant 77.5% increase in wound collagen deposition, as assessed by wound sponge granuloma hydroxyproline content. Administration of pharmacologic doses of recombinant murine TNF-alpha into subcutaneously inserted polyvinyl alcohol sponges resulted in an increase in collagen deposition (1594 +/- 117 vs 1014 +/- 49 and 1588 +/- 135 vs 1014 +/- 49 micrograms/100 mg sponge, for TNF-alpha in situ administration at a dose of 0.05 and 0.5 micrograms, respectively). This effect could be abolished by the simultaneous systemic treatment of the animals with the antiinflammatory drug indomethacin. The data suggest that the enhanced collagen deposition after TNF-alpha administration is a consequence of a nonspecific inflammatory activity that indirectly promotes collagen synthesis. The data also support the hypothesis that endogenous wound TNF-alpha down-regulates collagen synthesis during normal wound healing.
Animals↗
The effect of hemorrhagic shock on intestinal amino acid absorption in vivo.
Hemorrhagic shock causes a disproportionate decrease in portal blood flow which may adversely affect the barrier and absorptive functions of the intestine. The absorptive capacity of the small intestine was studied during shock induced by mild and severe hemorrhage in the rat by measurement of the uptake of a radiolabelled amino acid analog (aminoisobutyric acid: AIB). Hemorrhage resulted in a significant reduction in systemic blood pressure, portal blood flow, and the absorption of AIB from the small intestine. Resuscitation restored both blood pressure and portal blood flow. But a significant reduction in absorption of AIB persisted. This suggests that hemorrhage results in an inhibition of amino acid intestinal active transport which is not dependent on the mesenteric circulation. The reduced intestinal absorptive function has important implications for the route of administration of nutrition following hemorrhage and trauma.
Aminoisobutyric Acids↗
Laparoscopic cholecystectomy: experience in a district general hospital.
In many centres laparoscopic cholecystectomy has become the procedure of choice for symptomatic gallbladder stones. By comparison with conventional cholecystectomy it appears to be associated with minimal morbidity, shorter hospital stay, earlier return to work and a better cosmetic result. The present study reviews the results of the first 50 laparoscopic cholecystectomies performed at Altnagelvin Area Hospital.
Adult↗
Effect of age on wound healing in healthy human beings.
BACKGROUND: Although the elderly clinically have a higher rate of wound complications, the physiologic effect of age on wound healing in human beings is unknown. METHODS: Healthy young (18 to 55 years of age) and elderly (more than 65 years of age) human volunteers had a 2 x 2 cm, superficial, split-thickness wound created on the anterior aspect of the thigh, and the rate of epithelialization was assessed. For studies of fibroplasia, similar groups underwent subcutaneous implantation of polytetrafluoroethylene catheters, which were removed after 14 days. Biochemical analyses of the catheters included determinations of hydroxyproline, total alpha-amino nitrogen, and DNA. RESULTS: The elderly volunteers had a significant delay of 1.9 days in epithelialization. Analyses of the subcutaneously implanted catheters showed no difference in DNA content or hydroxyproline-accumulation; however, the young volunteers had a significantly higher amount of total alpha-amino nitrogen. CONCLUSIONS: In healthy humans, aging leads to delayed epithelialization. No effect of age on collagen synthesis was noted, although accumulation of wound noncollagenous protein was decreased. This decrease may impair the mechanical properties of scarring in aged human beings.
Adolescent↗
The wound environment as a regulator of fibroblast phenotype.
Fibroblasts are fundamental to successful wound healing. We hypothesized that the induction and regulation of various fibroblast functions (proliferation, collagen synthesis, and remodeling) are determined by the wound environment. We examined the effect of wound fluid (WF), as a reflection of the wound environment, on the phenotypic expression of normal dermal (NF) and wound-harvested fibroblasts (WHF). WF and WHF were obtained from implanted polyvinyl alcohol sponges in 10-day-old wounds. NF and WHF were used between one and three passages. Proliferative function was assayed in a microculture system using serum stimulation (n = 12). The proliferative response of both NF and WHF to serum was significantly reduced by the addition of 20% WF (17,261 +/- 1231 cpm vs 2704 +/- 1215 cpm for NF, P less than 0.05; and 15,391 +/- 3735 cpm vs 1701 +/- 816 cpm for WHF, P less than 0.05 in serum and WF, respectively). Total protein synthesis (measured by [3H]proline incorporation) was equal in both fibroblast types; however, the relative collagen synthesis (collagenase-digestible fraction) was markedly different (2.2 +/- 0.9% for NF vs 11.4 +/- 2% for WHF, P less than 0.05). Addition of WF markedly enhanced NF collagen synthesis to 9.4 +/- 2%, but had no effect on WHF. Mechanical and remodeling functions were assayed using fibroblast-populated collagen lattices. In serum, WHF contracted the lattices faster than NF (499 +/- 14 mm2 vs 770 +/- 30 mm2 at 24 hr, P less than 0.05, and 301 +/- 18 mm2 vs 540 +/- 21 mm2 at 72 hr, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Nitric oxide generation from L-arginine is required for optimal human peripheral blood lymphocyte DNA synthesis.
We examined whether L-arginine is a substrate for nitric oxide (NO) production by peripheral blood mononuclear cells (MNC) in vitro. Minimal extracellular arginine (0.04 mmol/L) is required for maximal lymphocyte proliferation after phytohemagglutinin stimulation. In the absence of arginine, proliferation was 41% of normal without loss of viability. In contrast, MNC total protein synthesis (as assessed by tritiated leucine incorporation) or lymphokine synthesis (interleukin-2, as assessed by cytotoxic lymphoid line (CTLL) proliferation) were not affected by the absence or presence of arginine in the medium. Exogenous nitric oxide provided as sodium nitroprusside could replace L-arginine for maximal blastogenic proliferation. The addition of NG-monomethyl-L-arginine (NMMA; 0.1 mmol/L), a specific inhibitor of the NO synthetic pathway, significantly reduced DNA synthesis both at 0 and 0.1 mmol/L arginine concentrations; this effect was reversed to 91% of normal by excess arginine (1.0 mmol/L). Homoarginine (0.1 mmol/L; a known substrate for NO production) partially substituted for arginine, and this effect was also abrogated by NMMA. Nitrite levels (an end product of NO metabolism) were reduced when L-arginine was absent or NMMA was added to L-arginine-containing media. Cytosol from phytohemagglutinin-stimulated MNC-enhanced cyclic guanosine monophosphate production in the presence of L-arginine as substrate. The data suggest that the inductive effects of L-arginine on MNC DNA synthesis are not related to its nutrient requirement for protein synthesis, but rather caused by its role as a substrate for NO production. MNC actively synthesize NO during mitogenic proliferation. NO appears to be a promoter of MNC DNA synthesis, probably by its well-known effect as an activator of guanylate cyclase, which increases cyclic guanosine monophosphate levels.
Arginine↗
Cloned murine T lymphocytes synthesize a molecule with the biological characteristics of nitric oxide.
Recently, activated neutrophils and macrophages have been shown to synthesize nitric oxide (NO) exclusively from L-arginine. We searched for the presence of this pathway in murine T cell clones. Using a platelet aggregation bioassay sensitive to NO, we demonstrate that IL2-stimulated CTLL and HT2 cells inhibit platelet aggregation, whereas unstimulated lymphocytes do not. This action can be inhibited by the specific NO synthase competitor NG-mono-methyl arginine, and only the L form of arginine or its analogue L-homoarginine are capable of providing substrate for NO synthesis.
Animals↗
Familial megaduodenum associated with hypoganglionosis.
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Adolescent↗
Management of blunt injuries of the axillary artery and the neck of the humerus: case report.
Axillary artery injury, a rare vascular complication of fracture of the humeral neck, is rendered unique by the concomitant subluxation of the humeral head. A coordinated vascular and orthopaedic surgical approach is necessary to reconstruct both the shoulder joint and the artery. The operative techniques chosen may determine long-term outcome.
Aged↗
Does preoperative computed tomography scanning aid assessment of oesophageal carcinoma?
In this study 50 patients (36 male, 14 female) with oesophageal carcinoma have been examined preoperatively by computed tomography. Three parameters were assessed, nodal involvement, invasion of adjacent organs, and metastatic disease. For all patients the computed tomography findings were correlated with the subsequent surgical and pathological findings. Sensitivity for both invasion and node involvement is low (36% to 67%). Specificity however, is high (85% to 95%). Computed tomography is therefore relatively reliable when it predicts a 'negative result' for either invasion or node involvement. However, its predictive value for a positive result is not as reliable.
Adult↗