Letter 2: Late complications after ligation and bypass for popliteal aneurysm (Br J Surg 2004; 91: 174-177).
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Aneurysm↗
Biomedical subjects
C Kyriakides
Publications and source records attributed to C Kyriakides.
A rare case of type A aortic dissection presenting as acute lower limb ischaemia.
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Accidents, Traffic↗
11-year experience with anatomical and extra-anatomical repair of mycotic aortic aneurysms.
BACKGROUND: We have reviewed our management, of both ruptured and non-ruptured, abdominal and thoraco-abdominal mycotic aneurysms in order to determine the safety and efficacy of in situ and extra-anatomical prosthetic repairs. METHODS: Data regarding presenting symptoms, investigations, operative techniques and outcome, were collected on patients treated at a singe centre over 11 years. RESULTS: There were 11 men and four women, with a median age of 70 years (range, 24-79). All but one patient were symptomatic and six had a contained leak on admission. In six patients no organisms were identified in either blood or tissue cultures. Pre-operative CT identified; four infra-renal, four juxta-renal, three (Crawford thoraco-abdominal) type IV, three type III and one type II, aortic aneurysms. Thirteen were repaired with in situ prostheses and two required axillo-femoral prosthetic grafts. There were four early deaths. All surviving patients have been followed-up for a median duration of 38 months (range 1/2-112 months). There were two late deaths at 3 months (juxta-renal) and at 2 years (type III), the latter relating to graft infection. CONCLUSIONS: In the absence of uncontrolled sepsis, repair of mycotic aortic aneurysms using prosthetic grafts can achieve durable results.
Aged↗
Recombinant soluble P-selectin glycoprotein ligand 1 moderates local and remote injuries following experimental lower-torso ischaemia.
BACKGROUND: A central role for the polymorphonuclear leucocyte (PMN) in skeletal muscle ischaemia-reperfusion has been demonstrated by the observation that PMN depletion reduced local and remote pulmonary vascular permeability. This study investigated the role of recombinant soluble P-selectin glycoprotein ligand-immunoglobulin fusion protein (rPSGL-Ig), a P- and E-selectin antagonist, in moderating injury. METHODS: Mice underwent 2 h of hindlimb ischaemia and 3 h of reperfusion. Muscle and lung vascular permeability index (PI) was assessed by extravasation of (125)I-radiolabelled albumin. Lung myelo peroxidase (MPO) activity was also measured. RESULTS: In mice treated with rPSGL-Ig 1 mg/kg before reperfusion (n = 12) muscle PI was reduced by 40 per cent, whereas it was moderated by 20 per cent in animals treated 30 min after reperfusion (n = 15). Lung PI in mice treated with rPSGL-Ig before (n = 12) and 30 min after (n = 15) reperfusion was reduced by over 99 and 98 per cent respectively. Lung MPO activity in mice treated with rPSGL-Ig before (n = 10) and 30 min after (n = 12) reperfusion was reduced by 68 and 58 per cent respectively. Treatment with rPSGL-Ig 1 h after reperfusion, or with m20ek.Fc 1 mg/kg (n = 9; negative control for rPSGL-Ig which is inactive for selectin binding) before reperfusion failed significantly to moderate local or remote organ injury. CONCLUSION: Selectin blockade moderated local skeletal muscle and remote lung injury following hindlimb ischaemia--reperfusion. Significantly, delayed antiselectin therapy also decreased injury.
Animals↗
Neutrophils, not complement, mediate the mortality of experimental hemorrhagic pancreatitis.
Chemoactivation of the neutrophil (PMN) via the complement system has been observed in many inflammatory conditions and is thought to play a pathogenic role in acute pancreatitis. This study examined the effects of PMN depletion in experimental hemorrhagic pancreatitis and tested the role played by complement. Severe pancreatitis was induced by a choline-deficient, 0.5% ethionine-supplemented diet in female Institute of Cancer Research (ICR) mice weighing 11-13 g. Neutropenia was induced by an antibody injection. Total complement depletion was achieved by tail vein injections of cobra venom factor (CVF). Serum amylase levels and local pancreatic injury were not significantly modulated by either PMN or complement depletion at 72 hours. Systemic and remote organ injury, assessed by the formation of ascites, hematocrit, and serum alanine aminotransferase levels, was significantly reduced in neutropenic mice but failed to be moderated by complement depletion. In addition, liver and lung myeloperoxidase activity was independent of complement depletion. At 5 days, mortality was zero in PMN-depleted mice. There was no improvement in survival in the CVF-treated group. Neutrophils are important in the systemic injury and mortality of severe pancreatitis. PMN chemoactivation involves mechanisms other than complement.
Acute Disease↗
Mast cells mediate complement activation after acid aspiration.
A significant role for the alternative complement pathway in acid aspiration has been demonstrated by the observation that C3 but not C4 genetic knockout mice are protected from permeability edema. Using mast cell-deficient mice (W/Wv), we tested the hypothesis that mast cells mediate complement activation after acid aspiration. Tracheostomy tubes were placed in anesthetized mice and 2 mL/kg 0.1 N HCL was instilled in the trachea. After 4 h, extravasation of 125I-albumin was used to calculate lung vascular permeability. The serum alternative complement pathway hemolytic activity was examined, and lung immunohistochemistry was performed. Lung permeability in W/Wv mice was 62% less than that of mast cell sufficient (+/+) animals and similar to +/+ mice treated with the chymase inhibitor chymostatin (65% decrease). Treatment of +/+ mice with D-PRO2,D-TRP(7,9)-Substance P, an antagonist to the neuropeptide substance P, reduced injury by 66%. Serum complement hemolytic activity was intact in injured w/wv mice and +/+ animals treated with chymostatin or dpdt-sp, but was decreased to 65% in the injured untreated +/+ group. Alveolar C3 deposition was intense in injured untreated +/+ mice but absent in the other groups. We interpret these data to indicate that mast cells mediate complement activation, via chymase degranulation, after acid aspiration. This mast cell activity likely is regulated by the release of substance P.
Animals↗
Moderation of skeletal muscle reperfusion injury by a sLe(x)-glycosylated complement inhibitory protein.
The role of the sialyl Lewis(x) (sLe(x))-decorated version of soluble complement receptor type 1 (sCR1) in moderating skeletal muscle reperfusion injury, by antagonizing neutrophil endothelial selectin interaction and complement activation, is examined. Mice underwent 2 h of hindlimb ischemia and 3 h of reperfusion. Permeability index (PI) was assessed by extravasation of 125I-labeled albumin. Neutrophil depletion and complement inhibition with sCR1 reduced permeability by 72% (PI 0.81 +/- 0.10) compared with a 42% decrease (PI 1.53 +/- 0.08) observed in neutropenic mice, indicating that part of the complement-mediated injury is neutrophil independent. sCR1sLe(x) treatment reduced PI by 70% (PI 0.86 +/- 0.06), an additional 20% decrease compared with sCR1 treatment (PI 1.32 +/- 0.08). Treatment with sCR1sLe(x) 0.5 and 1 h after reperfusion reduced permeability by 63% (PI 0.09 +/- 0.07) and 52% (PI 1.24 +/- 0.09), respectively, compared with the respective decreases of 41% (PI 1.41 +/- 0.10) and 32% (PI 1.61 +/- 0.07) after sCR1 treatment. Muscle immunohistochemistry stained for sCR1 only on the vascular endothelium of sCR1sLe(x)-treated mice. In conclusion, sCR1sLe(x) is more effective than sCR1 in moderating skeletal muscle reperfusion injury.
Animals↗
Sialyl Lewis(x) hybridized complement receptor type 1 moderates acid aspiration injury.
The potentially enhanced anti-inflammatory effects of the sialyl Lewis(x) (sLe(x))-decorated version of soluble complement receptor type 1 (sCR1) in moderating acid aspiration injury are examined. HCl was instilled in tracheostomy tubes placed in mice, and extravasation of (125)I-labeled albumin in bronchoalveolar lavage (BAL) fluid was used to calculate the vascular permeability index (PI). Neutrophil counts in BAL fluid and immunohistochemistry were performed. PI was moderated by 82% after treatment with sCR1sLe(x) compared with 54% in sCR1-untreated mice (P < 0.05). Respective reductions in PI in mice treated 0.5 and 1 h after acid aspiration with sCR1sLe(x) of 70 and 57% were greater than the decreases in PI of 45 and 38% observed in respective sCR1-treated groups (P < 0.05). BAL fluid neutrophil counts in sCR1sLe(x)-treated mice were significantly less than those in sCR1-treated animals, which were similar to those in untreated mice. Immunohistochemistry stained for sCR1 only on the pulmonary vascular endothelium of sCR1sLe(x)- but not sCR1-treated mice. In conclusion, sCR1sLe(x) moderates permeability by antagonizing complement activation and neutrophil adhesion. Delayed complement and neutrophil antagonism significantly reduces injury.
Animals↗
Endothelial selectin blockade attenuates lung permeability of experimental acid aspiration.
BACKGROUND: A central role for the polymorphonuclear leukocyte (PMN) in experimental acid aspiration has been demonstrated by the observation that PMN depletion reduced pulmonary vascular permeability. This study investigates the role of recombinant soluble P-selectin glycoprotein ligand-immunoglobulin fusion protein (rPSGL-Ig), a P- and E-selectin antagonist in moderating acid aspiration lung injury. METHODS: Tracheostomy tubes were placed in male C57BL/6 mice and 0.1 N HCl was instilled into the trachea at 2 mL/kg after intravenous injection of (125)I-albumin. After 4 hours the lung vascular permeability index (PI) and PMN accumulation in the bronchoalveolar lavage fluid were assessed. RESULTS: PI in neutropenic mice was 63% reduced compared with the untreated group and similar to the PI of mice treated with 1 mg/kg rPSGL-Ig before acid aspiration. PMN count of 19 +/- 5 in the bronchoalveolar lavage fluid in rPSGL-Ig treated mice was significantly less than the untreated group PMN count of 586 +/- 72. The respective PI in mice treated with rPSGL-Ig (1/2) hour and 1 hour after acid aspiration was 45% and 39% reduced compared with the untreated group. CONCLUSIONS: Endothelial selectin blockade is as effective as PMN depletion in moderating acid aspiration induced lung permeability. Delayed antiselectin therapy can decrease lung injury.
Animals↗
Neutrophil mediated remote organ injury after lower torso ischemia and reperfusion is selectin and complement dependent.
BACKGROUND: Lower torso ischemia and reperfusion leads to remote organ leukosequestration and injury. We now examine the intermediary role of selectins and complement in mediating lung and liver injury after hindlimb ischemia. METHODS: Mice underwent a 2-hour bilateral tourniquet hind-limb ischemia followed by 3 hours of reperfusion. RESULTS: Neutrophil depletion significantly decreased lung vascular permeability index (PI), measured by the extravasation of 125I-albumin, and liver injury as assessed by serum alanine aminotransferse levels. Lung PI and serum alanine aminotransferse levels were also reduced in mice treated with recombinant soluble P-selectin glycoprotein ligand-immunoglobulin fusion protein. Complement inhibition with soluble complement receptor type 1 decreased lung PI and serum alanine aminotransferse levels. C5-deficient mice exhibited a similar decrease in lung PI and liver injury. Lung and liver injury were restored in C5-deficient mice reconstituted with wild-type serum. CONCLUSION: Remote organ injury after lower torso reperfusion is selectin and complement dependent.
Alanine Transaminase↗
Soluble P-selectin moderates complement dependent injury.
P-selectin is an adhesion molecule expressed on activated endothelial and platelet membranes containing 9 short consensus repeats (SCRs) similar to the composition of complement regulatory proteins. In our murine model of intestinal ischemia and reperfusion where local injury is mediated by the classical complement pathway we hypothesized the SCRs would moderate the complement response. Confirmatory data were sought following hindlimb ischemia and reperfusion where injury is both complement- and neutrophil-mediated. Mice deficient in P-selectin (P-/-) were found to have similar intestinal and hindlimb permeability compared to normal wild types mice (P+/+). When reconstituted with P+/+ platelets, but not P-/- platelets, P-/- mice subjected to intestinal ischemia had a significant 29% decrease in permeability (P < 0.05) and after hindlimb ischemia the decrease was 33% (P<0.05). Reperfusion after intestinal ischemia led to a 76% fall in CH50 in P-/- compared to sham animals (P < 0.05) indicating complement activation and consumption, but only a 36% fall in animals reconstituted with P+/+ platelets (P < 0.05). Full-length, soluble P-selectin (sPsel) derived from processed platelets, but not the truncated version of sPsel has been shown to adhere to a heat labile fraction of serum and sensitized red blood cells thereby reducing Clq adherence to the sensitized red cell. From these data we conclude that sPsel moderates complement activation by competing with C1q binding to antibody, thereby limiting activation of the classical pathway that mediates murine reperfusion injury.
Animals↗
Soluble P-selectin moderates complement-dependent reperfusion injury of ischemic skeletal muscle.
P-selectin is an adhesion molecule expressed on activated endothelial and platelet surfaces. The function of the short consensus repeats (SCRs) of P-selectin, homologous with the SCRs of complement regulatory proteins is largely unknown. In a model of murine hindlimb ischemia where local reperfusion injury is partly mediated by IgM natural antibody and classical complement pathway activation, we hypothesized that human soluble P-selectin (sP-sel) would moderate the complement component of the inflammatory response. Infusion of sP-sel supernatant or purified (p) sP-sel prepared from activated human platelets, reduced ischemic muscle vascular permeability by 48% and 43%, respectively, following reperfusion. Hindlimb immunohistochemistry demonstrated negligible C3 staining colocalized with IgM in these groups compared with intense staining in the untreated injured mice. In vitro studies of mouse serum complement hemolytic activity showed that psP-sel inhibited the classical but not alternative complement pathway. Flow cytometry demonstrated that psP-sel inhibited C1q adherence to sensitized red blood cells. From these data we conclude that sP-sel moderates skeletal muscle reperfusion injury by inhibition of the classical complement pathway.
Animals↗
Screening of abdominal aortic aneurysm: a pragmatic approach.
In order to evaluate the feasibility of a selective screening programme for abdominal aortic aneurysm (AAA) within an urban setting and assess its impact on the expected increase in workload for the local hospital(s), a population based, prospective study was performed. A total of 4823 men aged 65 years were invited for ultrasound examination of the abdominal aorta between January 1993 and April 1997 as part of a general practice-based aneurysm screening programme covering two districts with a general hospital each. All examinations were carried out by senior radiographers using a portable B mode grey scale machine and a 3.5 MHz curvi-linear array probe. Patients with a maximum aortic diameter of over 3 cm were annually recalled, those with over 4 cm were referred to hospital for an out-patient's appointment. Those with AAA greater than 5 cm were considered for surgery. Of those approached, 3497 (72.5%) took part in the study, 1206 (25%) did not attend and 120 (2.5%) were excluded by their general practitioners (GPs) on medical grounds. Of the men taking part, 3130 (89.5%) had an aortic diameter equal to or less than 2.5 cm, 196 (5.6%) between 2.6 and 3.0 cm, and 171 (4.9%) had aortic diameters greater than 3 cm--29 of whom had AAA greater than 5 cm with a mean diameter of 6.0 cm (range 5.1-9.0 cm). Of 127 men with an initial diameter of 3.1-4.0 cm (mean progression in size of 2.3 mm/year), 22 enlarged to > 4 cm and 3 to > 5 cm. Of 24 men with an initial diameter of 4.1-5.0 cm, 6 enlarged to > 5 cm. Some 69 (2%) patients were referred to hospital requiring a total of 125 consultations (1.8 consultations per patient); 21 underwent surgery and one died from rupture whilst awaiting surgery. Five patients refused their operation and two failed to attend the clinic (all > 5 cm) but remain well to date. No patient died following surgery. We conclude that, screening for AAA in men at age 65 years within an urban setting is feasible and well received by patients and GPs. Screening does not lead to a huge increase in terms of outpatient appointments and operations for AAA.
Aged↗
Skeletal muscle reperfusion injury is mediated by neutrophils and the complement membrane attack complex.
The relative inflammatory roles of neutrophils, selectins, and terminal complement components are investigated in this study of skeletal muscle reperfusion injury. Mice underwent 2 h of hindlimb ischemia followed by 3 h of reperfusion. The role of neutrophils was defined by immunodepletion, which reduced injury by 38%, as did anti-selectin therapy with recombinant soluble P-selectin glycoprotein ligand-immunoglobulin (Ig) fusion protein. Injury in C5-deficient and soluble complement receptor type 1-treated wild-type mice was 48% less than that of untreated wild-type animals. Injury was restored in C5-deficient mice reconstituted with wild-type serum, indicating the effector role of C5-9. Neutropenic C5-deficient animals showed additive reduction in injuries (71%), which was lower than C5-deficient neutrophil-replete mice, indicating neutrophil activity without C5a. Hindlimb histological injury was worse in ischemic wild-type and C5-deficient animals reconstituted with wild-type serum. In conclusion, the membrane attack complex and neutrophils act additively to mediate skeletal muscle reperfusion injury. Neutrophil activity is independent of C5a but is dependent on selectin-mediated adhesion.
Animals↗
Membrane attack complex of complement and neutrophils mediate the injury of acid aspiration.
A significant role for the alternative complement pathway in acid aspiration has been demonstrated by the observation that C3 genetic knockout mice are protected from injury. Utilizing C5-deficient mice, we now test the role of the terminal complement components in mediating injury. Lung permeability in C5-deficient mice was 64% less than in wild-type animals and was similar to wild-type mice treated with soluble complement receptor type 1, which gave a 67% protection. Injury was fully restored in C5-deficient mice reconstituted with wild-type serum. The role of neutrophils was established in immunodepleted wild-type animals that showed a 58% protection. Injury was further reduced (90%) with the addition of soluble complement receptor type 1, indicating an additive effect of neutrophils and complement. Similarly, an additional protection was noted in C5-deficient neutropenic mice, indicating that neutrophil-mediated injury does not require C5a. Thus acid aspiration injury is mediated by the membrane attack complex and neutrophils. Neutrophil activity is independent of C5a.
Animals↗
Intestinal ischemia-reperfusion injury is mediated by the membrane attack complex.
BACKGROUND: The dependence of intestinal ischemia-reperfusion injury on the classical complement pathway has been shown with the complement antagonist (sCR1) and complement-specific knockout mice. Using C5 deficient mice, we show that the membrane attack complex mediates local injury. METHODS: Mice underwent intestinal ischemia-reperfusion. Albumin leak and histologic evidence were compared in wildtype mice, wildtypes treated with sCR1, neutrophil-depleted wildtypes, C5-deficient mice, and C5-deficient mice reconstituted with wildtype serum. Neutrophil tissue levels in injured C5-deficient and wildtype intestines were compared. RESULTS: C5-deficient mice had a reduction in injury similar to mice treated with sCR1. Injury was restored by reconstitution with wildtype serum. Wildtype injury was unaffected by neutrophil depletion. Injured intestines of C5-deficient and wildtype mice had similar neutrophil levels. Immunohistochemistry of wildtype and reconstituted C5-deficient mice demonstrated injured intestinal epithelium although C5-deficient mice and sCr1-treated mice were similar to sham mice. CONCLUSIONS: C5-deficient animals are protected from local injury. Injury is unaffected by neutrophil depletion, and the presence of neutrophils in injured tissue is independent of C5. Local injury is C5 dependent, but the action of C5a on granulocytes is not required. Therefore the membrane attack complex mediates local injury.
Animals↗
Day-case transfer of inpatients for diagnostic and therapeutic endoscopic retrograde cholangiopancreatography.
BACKGROUND: To use facilities flexibly and efficiently, a diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) service was offered to inpatients from referring hospitals on a day-case basis. METHODS: Patients were transferred by ambulance with a nurse escort and returned to the parent hospital after a short period of recovery. The activity of this service was audited. RESULTS: A total of 188 patients (70 men and 118 women of mean age 63.5 (range 22-94) years) were referred, 55 by physicians or geriatricians and 133 by surgeons from 19 hospitals up to 100 miles distant. Some 109 (58 per cent) had jaundice, 12 (6 per cent) cholangitis, seven (4 per cent) acute pancreatitis and 41 (22 per cent) abdominal pain. All patients arrived between 08:30 and 12:00 hours, all but 16 between 09:30 and 11:00 hours, and all but one with an escort; 129 patients travelled less than 10 miles. The mean time spent in the authors' hospital was 5.9 (range 2.2-9.5) h. The mean time spent away from the parent hospital by patient and escort was 7.0 (range 3.5-10) h. Cannulation failed in 12 patients (6 per cent), two with duodenal tumours. Sphincterotomy was performed in 70 cases, mechanical lithotripsy in seven and stents were inserted in 67. Nine patients were admitted, four for percutaneous stent insertion after failed ERCP and three for abdominal pain (one acute pancreatitis); two patients with sepsis and malignancy died after admission to this hospital. After return to the parent hospital, a further patient died following laparotomy for malignancy and five patients developed abdominal pain (three acute pancreatitis). CONCLUSION: These findings show that short-stay ERCP can be undertaken on transferred inpatients safely and efficiently without adverse effect on success or complication rates.
Adult↗