The Belfast approach to managing complex lower limb vascular injuries.

INTRODUCTION: Complex lower limb vascular injuries (CLVIs) in high-energy penetrating or blunt trauma are associated with an unacceptably high incidence of complications including amputation. Traumatic ischaemia and ischaemia-reperfusion injury (IRI) of skeletal muscle often lead to limb loss, the systemic inflammatory response syndrome (SIRS) which affects remote organs and even the potentially fatal multiple organ dysfunction syndrome (MODS). Surgical care of CLVIs everywhere, including Northern Ireland until 1978, was governed by an anxiety to restore arterial flow quickly often using expedient and flawed repair techniques while a damaged major vein was frequently ligated. MATERIALS AND METHODS: A new policy centred on early intraluminal shunting of both artery and vein, restoring arterial inflow and venous outflow, respectively, was introduced at the Regional Vascular Surgery Unit of The Royal Victoria Hospital, Belfast in 1979. It imposed a disciplined one-stage comprehensive approach to treatment involving a sequence of operative manoeuvres in which all damaged anatomical elements receive meticulous and optimal attention unshackled by time constraints. RESULTS: Comparisons drawn between the pre-shunt period of unplanned treatment (1969-1978) and the post-shunt period centred on the use of shunts (1979-2000) showed that early shunting of both artery and vein in both penetrating (P) and blunt (B) injuries significantly reduced the necessity for fasciotomy (P: p=0.016, B: p=0.02) and caused a significant fall in the incidence of contracture (P: p=0.018, B: p=0.02) and of amputation (P: p=0.009, P: p=0.012). CONCLUSIONS: The policy of early shunting of artery and vein in CLVIs has proved to be of great benefit in terms of significantly improved outcomes, better operative discipline and harmonious collaboration among the specialists involved.

Periods of low atmospheric pressure are associated with high abdominal aortic aneurysm rupture rates in Northern Ireland.

Seasonal and circadian variation in the incidence of ruptured abdominal aortic aneurysm (RAAA) has been reported. We explored the role of atmospheric pressure changes on rupture incidence and its relationship to cardiovascular risk factors. During a three year-period, 1st April 1998 and 31st March 2001, data was prospectively acquired on 144 Ruptured Abdominal Aortic Aneurysm (RAAA) presenting to the Regional Vascular Surgery Unit at the Royal Victoria Hospital, Belfast, Northern Ireland. For each patient the chronology of acute onset of symptoms and presentation to the regional vascular unit was recorded, along with details of standard cardiovascular risk factors. During the same period meteorological data including atmospheric pressure and air temperature were recorded daily at the regional meteorological research unit, Armagh. We then analyzed the monthly mean values for daily rupture incidence in relation to the monthly values for atmospheric pressure, pressure change and temperature. Furthermore atmospheric pressure on the day of rupture, and day preceding rupture, were also analyzed in relation to days without rupture presentation and between individual ruptures for various cardiovascular risk factors. Data demonstrated a significant monthly variation in aneurysm rupture frequency, (p<0.03, ANOVA). There was also a significant monthly variation in mean barometric atmospheric pressure, (p<0.0001, ANOVA), months with high rupture frequency also exhibiting low average pressures in the months of April (0.24 +/- 0.04 ruptures per day and 1007.78 +/- 1.23 mB) and September (0.16 +/- 0.04 ruptures per day and 1007.12 +/- 1.14 mB), respectively. The average barometric pressures were found to be significantly lower on those days when ruptures occurred (n=1127) compared to days when ruptures did not occur (n=969 days), (1009.98 +/- 1.11 versus 1012.09 +/- 0.41, p<0.05). Full data on risk factors was available on 103 of the 144 rupture patients and was further analyzed. Interestingly, RAAA with a known history of hypertension, (n=43), presented on days with significantly lower atmospheric pressure than those without, (n=60), (1008.61 +/- 2.16 versus 1012.14 +/- 1.70, p<0.05). Further analysis of ruptures grouped into those occurring on days above or below mean annual atmospheric pressure 1013.25 (approximately 1 atmosphere), by Chi-square test, revealed three cardiovascular risk factors significantly associated with low-pressure rupture, (p<0.05). Data represents mean +/- SEM, statistical comparisons with Student t-test and ANOVA. These data demonstrate a significant association between periods of low barometric pressure and high incidence of ruptured aneurysm, especially in those patients with known hypertension. The association between rupture incidence and barometric pressure warrants further study as it may influence the timing of elective AAA repair.

Radial artery mycotic pseudoaneurysm in a haemophiliac: a potentially fatal complication of arterial catheterization.

We present a case of radial artery pseudoaneurysm formation in a haemophiliac patient, which developed after radial artery cannulation. Haematologists and anaesthetists should be aware of this potentially fatal condition.

Non-detection of Chlamydia species in carotid atheroma using generic primers by nested PCR in a population with a high prevalence of Chlamydia pneumoniae antibody.

BACKGROUND: The association of Chlamydia pneumoniae with atherosclerosis is controversial. We investigated the presence of C. pneumoniae and other Chlamydia spp. in atheromatous carotid artery tissue. METHODS: Forty elective carotid endarterectomy patients were recruited (27 males, mean age 65 and 13 females mean age 68), 4 had bilateral carotid endarterectomies (n= 44 endarterectomy specimens). Control specimens were taken from macroscopically normal carotid artery adjacent to the atheromatous lesions (internal controls), except in 8 cases where normal carotid arteries from post mortem (external controls) were used. Three case-control pairs were excluded when the HLA DRB gene failed to amplify from the DNA. Genus specific primers to the major outer membrane protein (MOMP) gene were used in a nested polymerase chain reaction (nPCR) in 41 atheromatous carotid specimens and paired controls. PCR inhibition was monitored by spiking with target C. trachomatis. Atheroma severity was graded histologically. Plasma samples were tested by microimmunofluorescence (MIF) for antibodies to C. pneumoniae, C. trachomatis and C. psittaci and the corresponding white cells were tested for Chlamydia spp. by nPCR. RESULTS: C. pneumoniae was not detected in any carotid specimen. Twenty-five of 38 (66%) plasma specimens were positive for C. pneumoniae IgG, 2/38 (5%) for C. trachomatis IgG and 1/38 (3%) for C. psittaci IgG. CONCLUSIONS: We were unable to show an association between the presence of Chlamydia spp. and atheroma in carotid arteries in the presence of a high seroprevalence of C. pneumoniae antibodies in Northern Ireland.

Bactericidal/permeability-increasing protein attenuates systemic inflammation and acute lung injury in porcine lower limb ischemia-reperfusion injury.

OBJECTIVE: To investigate the role of recombinant bactericidal/permeability-increasing protein (rBPI21) in the attenuation of the sepsis syndrome and acute lung injury associated with lower limb ischemia-reperfusion (I/R) injury. SUMMARY BACKGROUND DATA: Gut-derived endotoxin has been implicated in the conversion of the sterile inflammatory response to a lethal sepsis syndrome after lower torso I/R injury. rBPI21 is a novel antiendotoxin therapy with proven benefit in sepsis. METHODS: Anesthetized ventilated swine underwent midline laparotomy and bilateral external iliac artery occlusion for 2 hours followed by 2.5 hours of reperfusion. Two groups (n = 6 per group) were randomized to receive, by intravenous infusion over 30 minutes, at the start of reperfusion, either thaumatin, a control-protein preparation, at 2 mg/kg body weight, or rBPI21 at 2 mg/kg body weight. A control group (n = 6) underwent laparotomy without further treatment and was administered thaumatin at 2 mg/kg body weight after 2 hours of anesthesia. Blood from a carotid artery cannula was taken every half-hour for arterial blood gas analysis. Plasma was separated and stored at -70 degrees C for later determination of plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 by bioassay, and IL-8 by enzyme-linked immunosorbent assay (ELISA), as a markers of systemic inflammation. Plasma endotoxin concentration was measured using ELISA. Lung tissue wet-to-dry weight ratio and myeloperoxidase concentration were used as markers of edema and neutrophil sequestration, respectively. Bronchoalveolar lavage protein concentration was measured by the bicinclinoic acid method as a measure of capillary-alveolar protein leak. The alveolar-arterial gradient was measured; a large gradient indicated impaired oxygen transport and hence lung injury. RESULTS: Bilateral hind limb I/R injury increased significantly intestinal mucosal acidosis, intestinal permeability, portal endotoxemia, plasma IL-6 concentrations, circulating phagocytic cell priming and pulmonary leukosequestration, edema, capillary-alveolar protein leak, and impaired gas exchange. Conversely, pigs treated with rBPI21 2 mg/kg at the onset of reperfusion had significantly reduced intestinal mucosal acidosis, portal endotoxin concentrations, and circulating phagocytic cell priming and had significantly less pulmonary edema, leukosequestration, and respiratory failure. CONCLUSIONS: Endotoxin transmigration across a hyperpermeable gut barrier, phagocytic cell priming, and cytokinemia are key events of I/R injury, sepsis, and pulmonary dysfunction. This study shows that rBPI21 ameliorates these adverse effects and may provide a novel therapeutic approach for prevention of I/R-associated sepsis syndrome.

Circulating neutrophil priming and systemic inflammation in limb ischaemia-reperfusion injury.

BACKGROUND: Recruitment and activation of neutrophils is a key step in the development of local and systemic injury in lower limb ischaemia-reperfusion. We hypothesis that increased circulating neutrophil priming is responsible for systemic inflammation. METHODS: Anaesthetised ventilated swine (n = 6 per group) underwent mid-line laparotomy and were randomised to control group or bilateral external iliac artery occlusion for two hours followed by two and a half hours reperfusion (I/R group). Using luminol, respiratory burst activity was assayed with a BioOrbit Luminometer to detect whole blood chemiluminescence (CL) by stimulation with phorbol 1,2-myristate 1,3-acetate (PMA) in the absence or presence of tumour necrosis factor (TNF) respectively. PMN priming is expressed as the ratio of whole blood CL in the presence of TNF to that without. We measured plasma interleukin(IL)-6 and tumour necrosis factor alpha by bioassay as a measure of systemic inflammation. The alveolar-arterial (A-a) gradient was measured using the formula [(A-a)gradient = fraction inspired O2 x 710-(arterial pCO2/0.8)-arterial pO2], it is a measure of lung function, a large gradient being indicative of impaired oxygen transport and hence lung injury. RESULTS: Lower limb I/R caused significantly greater PMN priming, 0.83 +/- 0.14, compared to control group, 0.22 +/- 0.04, (p < 0.001). Plasma IL-6, a reliable indicator of systemic inflammation, was significantly increased in I/R group after two and a half hours of reperfusion, 1295.0 (833.9-2073.0) pg/L, compared to control, 382.9 (367.4-568.3) pg/L, (p < 0.005). Plasma tumour necrosis factor alpha was significantly elevated after one hour of reperfusion in the I/R group, 86.8 (48.7-106.6) pg/ml, compared to the control group, 32.7 (0.9-42.8) pg/ml, (p < 0.01). (A-a) gradient was significantly increased after IRI, 407.97 +/- 53.13, compared to the control, 183.19 +/- 45.75, (p < 0.005). Mean pulmonary artery pressure was significantly greater after IRI, 38.80 +/- 4.87 mmHg, compared to control, 27.86 +/- 1.92 mmHg, (p < 0.005). Data represents mean +/- standard error mean or median (interquartile range), statistical comparisons using one-way Anova with Student's "t"-test and Kruskall-Wallis Anova with the Mann-Whitney U test. CONCLUSIONS: Priming of neutrophils increases their circulating respiratory burst activity and ability to induce tissue injury. Systemic PMN priming during hind limb ischaemia-reperfusion injury is associated with the systemic inflammatory response syndrome.

Recombinant bactericidal/permeability-increasing protein attenuates the systemic inflammatory response syndrome in lower limb ischemia-reperfusion injury.

OBJECTIVES: Hind limb ischemia-reperfusion (I/R) injury increases gut permeability, and resultant endotoxemia is associated with an amplified systemic inflammatory response syndrome leading to multiple organ dysfunction syndrome. We studied the potential role of recombinant bactericidal/permeability-increasing protein (rBPI(21) ), a novel antiendotoxin therapy, in modulating endotoxin-enhanced systemic inflammatory response syndrome in hind limb I/R injury. METHODS: In this prospective, randomized, controlled, experimental animal study, 48 male Wistar rats, weighing 300 to 350 g, were randomized to a control group (sham) and five groups undergoing 3 hours bilateral hind limb ischemia with 2 hours reperfusion (I/R) (n = 8 per group). The control and untreated I/R groups received thaumatin, a control-protein preparation, at 2 mg/kg. Treatment groups were administered rBPI(21) intravenously at 1, 2, or 4 mg/kg body weight at the beginning of reperfusion; an additional group was administered rBPI(21) intravenously at 2 mg/kg after 1 hour of reperfusion. Plasma interleukin-6 concentration was estimated by bioassay as a measure of systemic inflammation. Plasma endotoxin concentration was determined by use of an amebocyte lysate chromogenic assay. Crossreactive immunoglobulin G and M antibodies to the highly conserved inner core region of endotoxin were measured by use of an enzyme-linked immunosorbent assay. The lung tissue wet-to-dry weight ratio and myeloperoxidase concentration were used as markers of edema and neutrophil sequestration, respectively. RESULTS: I/R provoked highly significant elevation in plasma interleukin-6 concentrations (1351.20 pg/mL [860.16 - 1886.40 pg/mL]) compared with controls (125.32 pg/mL [87.76-157.52 pg/mL; P <.0001]), but treatment with rBPI(21) 2 mg/kg at onset of reperfusion (715.89 pg/mL [573.36-847.76 pg/mL]) significantly decreased interleukin-6 response compared with the nontreatment group ( P <.016). I/R increased plasma endotoxin concentrations significantly (21.52 pg/mL [6.20-48.23 pg/mL]), compared with control animals (0.90 pg/mL [0.00-2.30 pg/mL; P <.0001]), and treatment with rBPI(21) 4 mg/kg at reperfusion significantly decreased endotoxemia (1.30 pg/mL [1.20-2.20 pg/mL]), compared with the untreated group ( P <.001). The lung tissue myeloperoxidase level was significantly increased in the untreated I/R group (208.18% [128.79%-221.81%]), compared with in controls (62.00% [40.45%-80.92%; P <.0001]), and attenuated in those treated with rBPI(21) 2 mg/kg (129.54% [90.49%-145.78%; P <.05]). Data represent median and interquartile range, comparisons made with the nonparametric Mann-Whitney U test. CONCLUSIONS: These findings show that hind limb ischemia-reperfusion injury is associated with endotoxemia, elevations in plasma interleukin-6, and pulmonary leukosequestration. Treatment with rBPI(21) after ischemia reduces endotoxemia, the interleukin-6 response, and attenuates pulmonary leukosequestration in response to hind limb reperfusion injury.

Lower limb ischaemia-reperfusion injury causes endotoxaemia and endogenous antiendotoxin antibody consumption but not bacterial translocation.

BACKGROUND: It has been suggested that reperfusion of the acutely ischaemic lower limb alters gut permeability. The effect of lower limb ischaemia-reperfusion on systemic endotoxin and antiendotoxin antibody concentrations and the incidence of bacterial translocation was investigated. METHODS: Systemic endotoxin and antiendotoxin antibody concentrations were measured in five groups of male Wistar rats: control, after 3 h of bilateral hind limb ischaemia alone, and after 3 h of bilateral hind limb ischaemia followed by 1, 2 or 3 h of reperfusion. A second experiment examined translocation of indigenous bacteria following 2 h of reperfusion in a similar model. RESULTS: Ischaemia followed by reperfusion for 1, 2 or 3 h caused a significant increase in plasma endotoxin concentration to mean(s.e.m.) 10.0(3.0), 44.8(19.2) and 20.2(6.2) pg/ml compared with that in control animals (2.58(0.91) pg/ml) or animals in the ischaemia alone group (1.2(0.9) pg/ml) (P < 0.05). This was associated with a significant reduction in endogenous antiendotoxin antibody (immunoglobulin (Ig) G and IgM) concentration. No significant bacterial translocation was detected in any of the groups studied. CONCLUSION: These results demonstrate that a remote and isolated ischaemia-reperfusion injury to the lower limb, in the absence of infection or bacterial translocation, causes endotoxaemia. Further studies are needed to evaluate the role of endogenous antiendotoxin antibodies in this situation.

The use of tonometry to predict mortality in patients undergoing abdominal aortic aneurysm repair.

OBJECTIVE: To assess the reliability of intramucosal pH (pHi) of the sigmoid colon, IL-6 concentration and the APACHE II score in predicting outcome in patients undergoing elective abdominal aortic aneurysm repair. DESIGN: Prospective study. METHODS: In 42 patients, measurements were made of the sigmoid pHi with the silicone tonometer and plasma IL-6 by enzyme linked immuno-sorbent assay (ELISA). The daily postoperative APACHE II scores were also calculated. In 29 patients a preoperative left ventricular ejection fraction was determined by gated radionuclide angiography. RESULTS: Four out of 42 patients who were studied died. The lowest perioperative pHi, the peak postoperative IL-6 concentration and APACHE II scores were significantly different in the survivors in comparison to the non-survivors. In the non-survivors, the fall in pHi preceded the time of patient's demise by at least 4 days. Significant correlations were observed between changes in pHi, IL-6 and APACHE II. Using receiver operating characteristic curves, pHi was shown to be the most predictive of mortality compared to the other variables. The simplicity, speed and practicality of using the tonometer adds to its superiority over the latter measurements. No relationship was found between ventricular ejection fraction, pHi and outcome. CONCLUSION: Although the number of patients is small, these results support pHi as a valuable predictor of outcome and also suggest a role for the gut in initiating the IL-6 and physiological responses.

Expression of apoptosis-suppressing gene bcl-2 in human carotid body tumours.

That carotid body tumours have a genetic aetiology is suggested by the familial occurrence of the neoplasm. Environmental influences are also implied by the fact that the tumour is more common in those living at high altitudes. However, the mechanism of development of sporadic tumours occurring at sea level, which account for the majority of cases, remains unknown. It has become increasingly clear that the deregulation of programmed cell death is a critical component in multistep tumourigenesis. Previous studies have demonstrated a high frequency of bcl-2 expression in the tumours arising from cells derived from the neural crest and tumour cell lines of neural origin. This investigation was undertaken to determine whether similar molecular events occur in human carotid body tumours. Western and Northern analysis revealed that the tumours expressed the 26 kD protein and bcl-2 transcripts. Immunoperoxidase staining, using a monoclonal anti-bcl-2 antibody, revealed that 11 out of 13 specimens stained positively for bcl-2. These results suggest that the deregulation of programmed cell death may be a critical component in the multistep tumourigenesis of carotid body tumours and that the expression of oncoprotein bcl-2 may contribute to the generation of such tumours.

Lower limb ischaemia-reperfusion injury alters gastrointestinal structure and function.

BACKGROUND: It has been suggested that bowel permeability is altered following abdominal aortic aneurysm surgery. The effect of ischaemia-reperfusion injury to the lower limb on the morphological structure, neutrophil infiltration and permeability of the bowel was investigated. METHODS: Histological assessment of the bowel was undertaken in five groups of Wistar rats: control, 3 h of bilateral hind limb ischaemia and 3 h of bilateral hind limb ischaemia followed by 1, 2 or 3 h of reperfusion. Using an everted gut sac model and 14C-labelled polyethylene glycol, the effect of ischaemia-reperfusion on small bowel permeability was studied. RESULTS: The small bowel showed a significant decrease in mucosal thickness, villus height and crypt depth in animals subjected to ischaemia followed by 2-hr reperfusion (mean(s.e.m.) 420(15), 217(9) and 163(6) microns respectively) compared with controls (481(11), 245(6) and 195(6) microns) (P < 0.05). Neutrophil count within the lamina propria was similar in the different groups. A significant increase in mean(s.e.m.) 14C-labelled polyethylene glycol translocation was detected in animals subjected to ischaemia-reperfusion compared with controls (760(40) versus 560(27) c.p.m. per ml per h) (P < 0.05). CONCLUSION: These data suggest that reperfusion of acutely ischaemic extremities produces structural and functional changes in the small intestine, although these changes are not associated with increased neutrophil infiltration within the bowel wall.

Intramucosal acidosis and systemic host responses in abdominal aortic aneurysm surgery.

OBJECTIVES: To assess the specific host responses to systemic endotoxemia and tumor necrosis factor (TNF) activation after abdominal aortic aneurysm surgery by measuring antiendotoxin core antibodies (EndoCab) immunoglobulin (Ig)G and IgM, and soluble p55TNF receptor concentrations. The role of the gut in initiating these immune responses was evaluated by correlating the systemic markers to changes in the intramucosal pH of the sigmoid colon. DESIGN: Retrospective, reevaluation study. SETTING: Vascular unit of a university hospital. PATIENTS: Eleven patients who underwent abdominal aortic aneurysm repair surgery were selected from a larger patient cohort (n = 42) on the basis of their clinical outcome (four patients had fatal complications and seven patients had an uneventful recovery). INTERVENTIONS: After induction of anesthesia, intramucosal pH of the sigmoid colon was measured using tonometry. Blood samples were obtained from indwelling catheters or direct venipuncture preoperatively, during surgery, and daily until postoperative day 5. MEASUREMENTS AND MAIN RESULTS: Those patients who died developed intramucosal acidosis of the sigmoid colon intraoperatively. Significant consumption of both IgG and IgM EndoCab antibodies was found in all patients. By measuring the concentration of antibodies to a neutral antigen, i.e., tetanus toxoid, the consumption of IgG EndoCab antibody concentrations was shown to be a specific host response. In all patients, reciprocal changes in the serum concentrations of p55TNF receptor and interleukin (IL)-6 were observed. The percentage increase in p55TNF receptor and the concentration of IL-6 were significantly higher in the nonsurvivor group by 48 hrs. There were significant correlations between, intramucosal pH and EndoCab antibodies, intramucosal pH and p55 TNF receptor, and p55 TNF receptor and IL-6. CONCLUSIONS: The development of colonic ischemia is associated with a significant consumption of IgG EndoCab antibodies and a simultaneous increase in soluble p55TNF receptor. This study provides further support for the concept that gut-derived endotoxin and the generation of TNF may play a role in the pathogenesis of complications after abdominal aortic aneurysm surgery.

The generation of byproducts of lipid peroxidation following carotid endarterectomy.

The aim of this study was to determine whether free radical-induced lipid peroxidation occurs following transient carotid clamping. Jugular vein plasma levels of malondialdehyde (MDA) and diene conjugates (DC) were estimated in 24 patients undergoing carotid endarterectomy, at the beginning of the operation (To), just prior to clamping the carotid artery before the shunt was removed for closure of the arteriotomy (Ts), and at 30 (T30), 60 (T60), 120 (T120), 180 (T180) and 300 (T300) seconds after the clamps were released. Carotid clamp times were recorded. Significant elevations in the concentrations of both MDA and DC were observed at T60 after clamp release (MDA = 559 +/- 64 pmol/ml, DC = 428 +/- 32 units/ml), in comparison to concentrations at To (MDA = 408 +/- 34 pmol/ml, p < 0.01; DC = 374 +/- 28 units/ml, p < 0.05), returning to baseline at T300. There was a significant correlation between the percentage rise in MDA concentration and the duration of clamp-induced ischaemia (r = 0.45, p = 0.03). The significance of this burst of MDA and DC is unclear especially as the one patient who sustained a postoperative neurological deficit displayed no rise in the concentration of either. If this rise is related to free radical generation following ischaemia-reperfusion injury it may play an important role in influencing the clinical outcome in the patients.

Mortality following lower limb ischemia-reperfusion: a systemic inflammatory response?

Restoration of blood flow to an acutely ischemic lower limb may paradoxically result in systemic complications and unexpected mortality. It has been suggested that lower limb ischemia reperfusion alters gut permeability. In this study, using a rat model, we determined the effect of acute lower limb ischemia-reperfusion on mortality rate, bowel morphology, and circulating concentrations of endotoxin and the proinflammatory cytokine interleukin-6. Survival rate was compared in two groups of adult Wistar rats: (1) control group (n = 10); and (2) animals subjected to 3 hours of bilateral hind limb ischemia followed by reperfusion (n = 10). Both groups were observed under standard conditions for 4 days. In a second experiment three groups of animals were studied: (I) control (n = 12); (II) 3 hours of bilateral hind limb ischemia alone (n = 12); and (III) 3 hours of bilateral hind limb ischemia followed by 2 hours of reperfusion (n = 12). Animals subjected to bilateral hind limb ischemia followed by reperfusion had a significantly higher mortality rate (70%) than controls (0%) (p < 0.005). Morphometric assessment of the small bowel showed a significant decrease in mean mucosal thickness in the ischemia-reperfusion group compared with that in the group of controls and the ischemia-alone group (p < 0.05). Bilateral hind limb ischemia followed by reperfusion was associated with significantly increased plasma concentrations of endotoxin (p < 0. 05) and interleukin-6 (p < 0.0001) compared with that of controls and ischemia alone. These results indicate that reperfusion of the acutely ischemic lower limb is accompanied by structural changes in the gut mucosa associated with increased systemic endotoxin concentrations and cytokine activation. Mortality following reperfusion of the acutely ischemic limb may be related to a systemic inflammatory response triggered by endotoxin of gut origin.

Oncogene expression in carotid body tumors.

BACKGROUND: The genetic etiology of carotid body tumors is suggested by the familial occurrence of the neoplasm. Environmental influences are also implied by the fact that the tumor is more common in those living at high altitudes. However, the development of sporadic tumors occurring at sea level, which account for the majority of cases, remains unknown. METHODS: The clinical and pathologic features of 13 carotid body tumors excised in 13 patients were reviewed. Two patients had bilateral tumors, one with a strong family history, and two patients had recurrent carotid body tumors. All tumors were benign except for one that had local lymph gland metastases. All patients were followed up for a period ranging from 1 to 17 years. Each tumor was examined for the oncoproteins c-myc, bcl-2 c-erbB-2, c-erbB-3 and c-jun and for the proliferating cell nuclear antigen (PCNA) by immunohistochemistry. RESULTS: c-myc immunoreactivity was observed in all tumors and, in 12 of 13 cases, was present in more than 10% of tumor cells, bcl-2 immunoreactivity was found in 11 cases with 6 tumors exhibiting more than 10% immunopositive cells, c-jun expression was found in 5 cases with 3 tumors containing more than 10% immunopositive cells. Only two tumors were positive for c-erb-B2 immunoreactivity with a cytoplasmic staining pattern. One tumor was positive for c-erb-B3. CONCLUSIONS: The oncogenes c-myc, bcl-2 and c-jun, are abnormally expressed in some carotid body tumors. Their expression may contribute to the genesis of carotid body tumors.

Effect of low-dose dopamine on sigmoid colonic intramucosal pH in patients undergoing elective abdominal aortic aneurysm repair.

The effect of low-dose dopamine administration on intramucosal pH (pHi) of the sigmoid colon and on postoperative function of various organs in patients undergoing elective abdominal aortic aneurysm repair was examined. Nineteen patients were randomized to two groups; nine received dopamine at a rate of 3 micrograms per kg per min for 24 h from induction of anaesthesia and ten control patients received fluids without dopamine. pHi was measured with a silicone tonometer and daily samples of blood were taken for measurement of liver transaminase activity, arterial oxygen saturation and creatinine concentration. Mean(s.e.m.) pHi fell to a significantly lower minimum value in those receiving dopamine compared with control patients (6.86(0.10) versus 7.11(0.08), P < 0.05). Five of the nine patients given dopamine developed intramucosal acidosis compared with only one of the ten control patients (P = 0.06). After operation the mean(s.e.m.) aspartate transaminase concentration in patients given dopamine rose from 33(2) to 80(17) units/l (P < 0.01); in control patients it rose from 32(3) to 59(16) units/l (P = 0.054). No differences between the groups was observed in the postoperative ratio of arterial oxygen saturation to inspired oxygen fraction or creatinine concentrations. These results indicate that dopamine has no beneficial effect on bowel mucosal oxygenation and function of the various organs in patients undergoing aortic aneurysm repair.