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Biomedical subjects

K R Gardiner

Publications and source records attributed to K R Gardiner.

At least 19 recordsLinked to original sources
PubMed2003

The effect of lower limb ischaemia-reperfusion on intestinal permeability and the systemic inflammatory response.

OBJECTIVES: a relationship has been demonstrated between increased intestinal permeability, endotoxaemia and the development of the systemic inflammatory response syndrome (SIRS) after aortic surgery. The aim of this study was to evaluate whether isolated lower limb ischaemia-reperfusion (I/R) injury affects intestinal mucosal barrier function and cytokine release. PATIENTS AND METHODS: four groups of patients were investigated, group I, patients with critical limb ischaemia (CLI) undergoing infra-inguinal bypass surgery (n=18); group II, patients with intermittent claudication (IC) undergoing infra-inguinal bypass surgery (n=14); group III, patients with CLI unsuitable for arterial reconstruction, undergoing major amputation (n=12); and group IV, patients undergoing carotid endarterectomy for symptomatic carotid stenosis (n=13). Intestinal permeability, endotoxaemia and urinary soluble tumour necrosis factor receptors were assessed (p55TNF-R). RESULTS: an increase in intestinal permeability was observed on the 3rd postoperative day only in CLI group. This was found to correlate with arterial clamp time. Patients who had a femoro-distal bypass had significantly higher intestinal permeability compared to those who had femoro-popliteal bypass. Endotoxaemia was not detected in any of the groups. Postoperative urinary p55TNF-R concentrations were significantly higher in CLI group compared to the other groups. These did not correlate with the increased intestinal permeability. CONCLUSIONS: our results support the hypothesis that revascularisation of critically ischaemia limbs leads to intestinal mucosal barrier dysfunction and cytokine release. They also suggest that the magnitude of the inflammatory response following I/R injury is related to the degree of initial ischaemia.

Aged↗
PubMed2002

Vacuum assisted closure system in the management of enterocutaneous fistulae.

BACKGROUND: A very important yet often troublesome element in the conservative management of enterocutaneous fistulae is the protection of the surrounding skin from contact with the effluent. This report describes the successful use of a vacuum assisted closure (VAC) system in dealing with this problem. METHODS: The results of using the VAC system were studied in three patients with moderate or high volume output enterocutaneous fistulae where conventional treatment had failed to prevent skin excoriation. RESULTS: The VAC system was found to be highly effective in controlling fistula effluent and in promoting healing of excoriated skin in all three patients. Complete healing of the fistula was also achieved in two of the three patients. CONCLUSION: The VAC system can be an effective and economically viable method of containing fistula effluent and protecting the skin of patients with enterocutaneous fistulae. Contrary to conventional thought, the VAC system may also actually promote healing of the fistula.

Adult↗
PubMed2002

Successful colonoscopy; completion rates and reasons for incompletion.

Factors such as poor bowel preparation or obstructing colonic disease may confound the reporting of colonoscopy completion rates, as these factors are outside of the control of the endoscopist performing the procedure. By adjusting for these factors when calculating a colonoscopy completion rate, it may be possible to make a more accurate assessment of a unit's or individuals' competence. Details of two thousand two hundred and sixteen colonoscopies performed by four consultants and their trainees between 1993-2000 were analysed retrospectively from a prospective endoscopy database. Crude (all cases) and adjusted (excluding poor bowel preparation and disease as causes of incompletion) rates were recorded for each sex, and by age according to cause. Overall crude and adjusted completion rates were 77.9% and 85.0% respectively. There was a significant difference between male and female completion rates due to a difference in the incidence of excess looping and intolerance of the procedure (adjusted rate 88.9% in males vs. 81.6% in females, p<0.05). There was a non-significant trend to lower completion rates in patients over 75 years of age compared to younger patients. Completion rates were significantly higher following bowel resection (adjusted rates 93.5% vs. 82.8%, p<0.05). There was no significant difference between completion rates for inpatient and outpatient referrals (P=0.36). Reporting colonoscopy completion rates by adjusting for factors such as poor bowel preparation and obstructing colonic disease allows for direct comparisons of completion rates reported by different units. Reporting completion rates in this way also highlights the effect of inadequate bowel preparation on successful colonoscopy.

Adolescent↗
PubMed2001

Tumour necrosis factor inhibitors reduce the acute-phase response in hapten-induced colitis.

BACKGROUND: Tumour necrosis factor (TNF) alpha has been implicated in the pathogenesis of inflammatory bowel disease. The aim of this study was to assess the contribution of TNF to the pathogenesis of hapten-induced colitis. METHODS: Colitis was induced in Wistar rats using intracolonic instillation of the hapten trinitrobenzenesulphonic acid (TNBS) in ethanol. Animals were treated with monoclonal anti-TNF antibody (cTN3), an idiotype control antibody (CB0006) or pentoxifylline. Colonic and systemic inflammation was assessed quantitatively. RESULTS: The use of either TNF inhibitor attenuated the acute-phase response in the early stages of colitis. Median (interquartile range (i.q.r.)) alpha 2-macroglobulin levels were reduced in animals pretreated with cTN3 (421 (279-915) micromol/ml) or pentoxifylline (567 (253-1454) micromol/ml) compared with levels in untreated colitic animals (1552 (1406-1998) micromol/ml) (P < 0.001 and P = 0.006, respectively). In established colitis, administration of anti-TNF antibodies resulted in an increase in median (i.q.r.) weight gain (percentage change in body-weight): colitic animals -2.3 (- 5.5 to 9.2) per cent versus cTN3-treated rats 15 (7.5-16.7) per cent; P < 0.05. CONCLUSION: The systemic response to TNBS-induced colitis appears to be at least partially dependent on TNF. This study did not provide evidence to support a role for TNF in the pathogenesis of colonic inflammation in this model. Presented in part to the 86th meeting of the Surgical Research Society in Nottingham, UK, 9-11 July 1997, and published in abstract form as Br J Surg 1997; 84: 1613

Acute-Phase Reaction↗
PubMed2001

Extraperitoneal approach reduces neutrophil activation, systemic inflammatory response and organ dysfunctionin aortic aneurysm surgery.

OBJECTIVES: to compare the effects of transperitoneal and extraperitoneal approaches on systemic inflammatory response, neutrophil activation and organ dysfunction in elective abdominal aortic aneurysm (AAA) repair. PATIENTS AND METHODS: twenty patients admitted for elective infrarenal AAA repair were prospectively randomised into transperitoneal (n =10) or extraperitoneal ( n =10) groups. Neutrophil activation was assessed by measuring the plasma levels of neutrophil elastase/alpha(1)-anti-trypsin complexes before surgery, intraoperatively and at 6 h, 12 h, 24 h and then daily after surgery. Venous blood samples for estimation of liver function tests, full blood counts, urea and electrolytes and arterial samples for blood gas analysis were taken daily from preoperatively to day 5 after surgery. Multiple organ dysfunction (MOD) and systemic inflammatory response (SIR) scores were calculated daily. RESULTS: the concentrations of neutrophil elastase/alpha(1)-anti-trypsin complexes were significantly higher in the transperitoneal group at 6 h after surgery compared to the extraperitoneal group (799(455-921) ng/ml (median(i.q.r.)) vs 307(171-395) ng/ml, p<0.005), and at 12 h (397(364-936) ng/ml vs 319(134-352) ng/ml, p <0.05). The MOD scores were significantly higher in the transperitoneal group in comparison to the extraperitoneal group at day 1 (2.5(2-3.3) vs 1(0-1), p<0.001) and day 2 (2.5(2-3.3) vs 1(0-1), p <0.001). The SIR scores were also significantly higher at day 1 (1(0-2) vs 0, p <0.01), day 2 (1.5(0-2.3) vs 0, p <0.01), and day 3 (1(0-1) vs 0, p <0.05). CONCLUSIONS: neutrophil activation, systemic inflammatory response and organ dysfunction are increased in elective AAA repair when a transperitoneal approach is used. This may be related to intestinal manipulation and mesenteric traction which are reduced in the extraperitoneal approach.

APACHE↗
PubMed2001

Flexible sigmoidoscopy and the changing distribution of colorectal cancer: implications for screening.

BACKGROUND AND AIMS: There has been a significant proximal shift in the distribution of colorectal cancer (CRC) in Northern Ireland over recent decades. The aim of this study was to investigate the potential implications of this proximal shift in CRC distribution on the efficacy of flexible sigmoidoscopy (FS) as a screening tool. PATIENTS AND METHODS: The site distribution of 5153 CRCs was available from the Northern Ireland Colorectal Cancer Register for the period 1990-1997. Similar data on 1241 CRCs between 1976 and 1978 were available from a previous study. Data on the site reached by FS were obtained from a prospectively collected endoscopy database at one of Northern Ireland's main teaching hospitals for the period 1993-1998. RESULTS: There was a significant proximal shift in CRC distribution between the two periods (23.5% proximal to the splenic flexure between 1976 and 1978 v 36.7% between 1990 and 1997; p<0.001). The descending colon was visualised during 74.4% of FS examinations. By combining the observed extent of FS examination with CRC site distribution, it was calculated that FS could have visualised 68.8% of CRCs between 1976 and 1978 but only 56.0% between 1990 and 1997. Extrapolating these data to a Northern Ireland screening programme involving FS and faecal occult blood testing suggests that significantly more CRCs could have been detected between 1976 and 1978 than between 1990 and 1997 (51.7% v 48.2%, respectively; p=0.03). CONCLUSIONS: This study confirms the previously documented left to right shift in CRC distribution in Northern Ireland and demonstrates that if this shift continues, FS will become less successful as a screening tool than is currently predicted.

Colorectal Neoplasms↗
PubMed2001

Progress in the understanding and treatment of chronic anal fissure.

BACKGROUND: Chronic anal fissure is a common and painful condition associated with internal anal sphincter hypertonia. Reduction of this hypertonia improves the local blood supply, encouraging fissure healing. Surgical sphincterotomy is very successful at healing these fissures but requires an operation with associated morbidity. Temporary reduction in sphincter tone can be achieved on an outpatient basis by applying a topical nitric oxide donor (for example, glyceryl trinitrate) or injecting botulinum toxin into the anal sphincter. METHODS: A Medline database was used to perform a literature search for articles relating to the non-surgical treatment of chronic anal fissure. RESULTS: Review of the literature shows botulinum toxin injection to be more effective at healing chronic anal fissures than topical glyceryl trinitrate. Topical isosorbide dinitrate has not been directly compared with either of these two agents but has a healing rate approaching that of botulinum toxin injection. The main side effect of botulinum toxin injection is temporary faecal incontinence in approximately 2% of cases, whereas topical nitrates cause headaches in 20%-100% of cases. No long term side effects were identified with any of the medical treatments. CONCLUSION: Chemical sphincterotomy is an effective treatment for chronic anal fissure and has the advantages over surgical treatment of avoiding long term complications (notably incontinence) and not requiring hospitalisation.

Administration, Topical↗
PubMed2001

Extraperitoneal approach reduces intestinal and renal dysfunction in elective abdominal aortic aneurysm repair.

BACKGROUND: Intestinal mucosal barrier dysfunction observed in patients undergoing transperitoneal abdominal aortic aneurysm (AAA) repair may contribute to the development of the systemic inflammatory response syndrome and dysfunction of various organs. The aim of this study is to investigate whether an extraperitoneal approach reduces intestinal mucosal barrier and renal dysfunction in elective infrarenal AAA repair. METHODS: Twenty patients admitted for elective infrarenal AAA repair were randomized into either the transperitoneal approach (n=10) or the extraperitoneal approach (n=10). Intestinal permeability was measured preoperatively, and at day 1 and day 3 after surgery using the lactulose/mannitol test by calculating the differential urinary excretion ratio of the two sugars after oral administration. Renal dysfunction was assessed by measuring the urinary albumin/creatinine ratio (ACR) at the same time points. RESULTS: Intestinal permeability was significantly increased in the transperitoneal group at day 1 [0.124+/-0.035 (mean+/-s.e.m.)] compared to the preoperative level (0.020+/-0.003), (p=0.001) and to the extraperitoneal group at day 1 (0.025+/-0.008), (p<0.05) which showed no change in comparison with the preoperative level (0.020+/-0.003). The ACR was also significantly increased in the transperitoneal group at day 1 (16.69+/-5.12) compared to the preoperative level (5.71+/-2.89), (p<0.05) and to the extraperitoneal group at day 1 (4.33+/-1.49), (p<0.05) which showed no significant change at any of the times examined. No correlation was observed between the lactulose/mannitol ratio and the albumin/creatinine ratio, or between age, operating time, aortic clamping time, amount of blood lost or blood transfused. CONCLUSIONS: These results support the suggestion that minimising intestinal manipulation using an extraperitoneal approach in AAA repair preserves intestinal mucosal barrier and renal glomerular functions.

Aged↗
PubMed2000

Interleukin 10-deficient colitis: new similarities to human inflammatory bowel disease.

BACKGROUND: Interleukin (IL) 10 is a potent anti-inflammatory cytokine. Disruption of the IL-10 gene in C57/Black6 mice results in enterocolitis in the presence of intestinal bacteria. This study investigated gut mucosal barrier function sequentially during the development of colitis in this model. METHODS: Animals were bred in specific pathogen-free conditions and transferred to conventional housing at 4 weeks. Mice were evaluated at 6, 8, 10, 12, 14 and 15 weeks of age. Barrier function was assessed by measuring intestinal permeability and antibody response to systemic endotoxaemia (antibody to the core glycolipid region of lipopolysaccharide; EndoCAb). Colons were harvested and a histological injury score (HIS) was calculated. RESULTS: The HIS increased progressively until 12 weeks, with an associated increase in intestinal permeability, and immunoglobulin (Ig) M and IgG EndoCAb. The HIS correlated positively with both intestinal permeability and IgM and IgG EndoCAb. Intestinal permeability showed a positive correlation with EndoCAb. CONCLUSION: IL-10 knockout mice develop colitis with an associated disturbance in gut mucosal barrier function, as measured by increased permeability and endotoxaemia. The colitis found in the IL-10 knockout mouse shares these histological, physiological and biochemical features with human inflammatory bowel disease and is therefore suitable for therapeutic trials. A measure of endotoxaemia correlated directly with intestinal permeability in this model.

Animals↗
PubMed2000

Intestinal manipulation during elective aortic aneurysm surgery leads to portal endotoxaemia and mucosal barrier dysfunction.

OBJECTIVES: to investigate the effect of intestinal manipulation on intestinal permeability and endotoxaemia during elective abdominal aortic aneurysm (AAA) surgery. DESIGN: prospective randomised controlled study. PATIENTS AND METHODS: fourteen patients undergoing elective infrarenal AAA repair were randomised into either the transperitoneal (n=7) or extraperitoneal approach (n=7). Intestinal permeability was measured preoperatively (PO), and at day 1 (D1) and day 3 (D3) after surgery using the lactulose/mannitol absorption test. Portal and systemic blood samples were taken before clamping, at completion of proximal and distal anastomoses and immediately before abdominal wound closure, for endotoxin measurement using the chromogenic limulus amoebocyte lysate assay. RESULTS: intestinal permeability was significantly increased at D1 (0.107+/-0.04 (mean+/-S.E.M.)) in the transperitoneal group compared to the PO level (0.020+/-0.004, p<0.05) and to the extraperitoneal group at D1 (0.020+/-0.004, p<0.05) which showed no change in comparison with the PO level. No correlation was seen between increased intestinal permeability and aortic clamp time, operation time, amount of blood lost or transfused. However, a significantly higher concentration of portal endotoxin was detected intraoperatively in the transperitoneal group of patients in comparison to the extraperitoneal group (p<0.05). There was a significant positive correlation between portal endotoxaemia and intestinal permeability (r(s)=0.955 p=0.001). CONCLUSION: an increase in intestinal permeability and a greater degree of portal endotoxaemia are observed during transperitoneal approach to the aorta. This suggests that intestinal manipulation may impair gut mucosal barrier function and contribute to the systemic inflammatory response seen in AAA surgery.

Aged↗
PubMed2000

Probiotic therapy fails to improve gut permeability in a hapten model of colitis.

BACKGROUND: Studies in clinical and experimental inflammatory bowel disease (IBD) have shown disturbances in intestinal bacterial flora with an increase in potentially pathogenic and a decrease in protective organisms. It was hypothesized that Lactobacillus plantarum species 299 (LP299), a probiotic, would ameliorate colitis and improve intestinal permeability in experimental colitis. This study investigated the effect of LP299 in the trinitrobenzenesulfonic acid/ethanol (TNBS/E) rat model of colitis. METHODS: Twelve week old male Wistar rats were randomized to receive rectal instillates of either TNBS/E (n = 48) or saline (n = 16). For the next 7 days the animals were gavaged with 2.5 ml of oat fibre suspension containing 10(9) colony forming units (CFU) of LP299 (LP299/OF), oat fibre suspension alone (OF) or no treatment. At the end of the experiment rats received radiolabelled polyethylene glycol and urine was collected for 24 h to assess permeability. Animals were then anaesthetized and colons were harvested for colon macroscopic scoring (CMS). RESULTS: TNBS/E per rectum resulted in a greater CMS (P < 0.001) and gut permeability (P = 0.006) than saline. Administration of LP299/OF or oat fibre alone did not result in a reduction in CMS or gut permeability when compared to colitic controls. CONCLUSIONS: LP299/OF, when administered after TNBS instillation, does not reduce the severity of colitis or improve gut permeability in this hapten model of colitis.

Animals↗
PubMed2000

Oral administration of inducible nitric oxide synthase inhibitors reduces nitric oxide synthesis but has no effect on the severity of experimental colitis.

BACKGROUND: Increased concentrations of nitrate and nitrite (the breakdown products of nitric oxide) in the serum and faeces of patients with inflammatory bowel disease (IBD) suggests that increased synthesis of nitric oxide occurs in IBD. The aim of this study was to assess aminoguanidine (AMG), a selective inhibitor of inducible nitric oxide synthase, with regard to its effectiveness as a nitric oxide inhibitor and as a modulator of inflammation in trinitrobenzene sulfonic acid (TNBS)-induced colitis. MATERIALS AND METHODS: Colitis was induced in Wistar rats. Selective (AMG) and non-selective (1-nitroso-arginine methyl ester (1-NAME)) inhibitors of nitric oxide synthase were given in the drinking water. Colonic citrulline and arginine concentrations were assessed using high-performance liquid chromatography. The severity of colitis was assessed by a macroscopic scoring system. RESULTS: Both 1-NAME and AMG successfully reduced nitric oxide synthesis. There was no evidence of substrate depletion in the colonic wall. Neither of the agents reduced the severity of colonic inflammation. CONCLUSIONS: Oral administration of nitric oxide synthase inhibitors reduced nitric oxide synthesis in the colonic wall. This study does not provide evidence to support a role for nitric oxide in the pathogenesis of colonic inflammation in TNBS colitis.

Administration, Oral↗
PubMed2000

Ischemic preconditioning ameliorates ischemia- and reperfusion-induced intestinal epithelial hyperpermeability in rats.

We hypothesized that ischemic preconditioning (IPC) would ameliorate ischemia (I) and reperfusion (R)-induced intestinal mucosal hyperpermeability and that this effect would be diminished by lowering local adenosine concentrations using adenosine deaminase (ADA). The small intestine of anesthetized rats (group 1; n = 6) was divided into six 10-cm segments (A1-F1) each perfused by a different set of mesenteric branches. Segments D1-F1 were subjected to 3 cycles of IPC (2 min I/5 min R). Segments A1, B1, and C1 were excised at baseline, after 60 min of I (160), and after 60 min of I followed by 60 min of R (160/R60), respectively. Segment D1 was excised immediately after the last cycle of IPC, E1 was excised at 160 after IPC, and F1 was excised at 160/R60 after IPC. In group 2 (n = 6), the intestine was divided into five 10-cm vascularly isolated segments (A2-E2). Segment A2 was resected at baseline. The lumen of the remaining segments was filled with ADA (32 U/50 cm). Segment B2 was removed at the end of the experiment having been exposed to ADA for 150 min (ADA150). Segments C2, D2, and E2 were subjected to IPC. Segment C2 was excised immediately thereafter. Segments D2 and E2 were excised at 160 and 160/R60, respectively. Intestinal permeability to fluorescein isothiocyanate-labeled dextran (molecular weight 4000 D) was assessed ex vivo by using an everted gut sac method. IPC ameliorated intestinal hyperpermeability induced by 160 (43.0+/-7.6 vs. 70.4+/-8.3 nLmin/cm2; P = 0.024) and 160/R60 (20.2+/-3.7 vs. 69.5+/-10.8 nL/min/cm2; P= 0.003). IPC prevented ischemia-induced reduction in villus height. Treatment with ADA partially reversed the protective effect of IPC on the changes in permeability and villus height induced by I/R. We conclude that IPC partially protects against mucosal barrier dysfunction in rats subjected to mesenteric I/R. Adenosine is a mediator of IPC in the gut mucosa, but other factors also may be important.

Adenosine↗
PubMed1999

The gastrointestinal tract as a barrier in sepsis.

The gastrointestinal tract is an organ of digestion and absorption which is metabolically active and has specific nutrient requirements. In health, it has an additional function as a major barrier, protecting the body from harmful intraluminal pathogens and large antigenic molecules. In disease states, such as sepsis when the mucosal barrier is compromised, micro-organisms and their toxic products gain access to the portal and systemic circulations producing deleterious effects. Under these circumstances, systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) develop leading to deterioration and death of the patient in the intensive care unit. Therapeutic strategies for such patients in the intensive care unit aim to support general immune function and maintain the structure and function of the gastrointestinal tract. For these therapies to be successful, the underlying septic or necrotic focus must be ablated using appropriate surgical or other invasive techniques.

Digestive System↗