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D Bouchier-Hayes

Publications and source records attributed to D Bouchier-Hayes.

At least 91 records · Page 5Linked to original sources

Role of nitric oxide in lung injury associated with experimental acute pancreatitis.

This study evaluated the effect of varying the synthesis of nitric oxide with sodium nitroprusside or N-nitro-L-arginine methyl ester (L-NAME) in a pancreatitis-lung injury model. Rats (n = 45) were randomized to control or caerulein-induced pancreatitis groups, treated with saline, sodium nitroprusside (0.4 micrograms/kg) or L-NAME (10 mg/kg). Myeloperoxidase activity was used as a measure of neutrophil infiltration. Wet to dry (W:D) lung weight and bronchoalveolar lavage (BAL) protein concentrations were used to assess vascular leakage. Pancreatitis was shown to induce pulmonary neutrophil influx: mean(s.e.m.) myeloperoxidase activity 6.79(0.5) units/g in caerulein-treated animals versus 2.08(0.5) units/g in controls (P < 0.001). Animals with pancreatitis showed increased microvascular leakage compared with controls (mean(s.e.m.) W:D lung weight 7.01(0.5) versus 2.85(0.2), P < 0.001; BAL protein concentration 2539(222) versus 347(32) micrograms/ml, P < 0.001). Compared with the saline-treated pancreatitis group, these changes were reduced by sodium nitroprusside (mean(s.e.m.) myeloperoxidase activity to 2.5(0.4) units/g, P < 0.001; W:D lung weight to 3.8(0.37), P < 0.001; BAL protein concentration 1389(182) micrograms/ml, P < 0.05). L-NAME exacerbated the pancreatitis-induced pulmonary oedema (W:D lung weight increased to 11.96(0.6), P < 0.001), protein leakage (BAL protein concentration rose to 3707(309) micrograms/ml, P < 0.05) and neutrophil infiltration (myeloperoxidase activity increased to 9.01(0.3) units/g, P < 0.05). These data suggest that, in vivo, nitric oxide inhibits pancreatitis-induced lung injury, possibly in part by inhibiting pulmonary neutrophil influx.

Acute Disease↗

Taurolidine, an antilipopolysaccharide agent, has immunoregulatory properties that are mediated by the amino acid taurine.

Taurolidine has bactericidal and antilipopolysaccharide properties. It is broken down into the amino acid taurine, which has been shown to modulate intracellular calcium activity, a critical component in the priming and activation of macrophages and polymorphonuclear leukocytes. We hypothesized that taurolidine may function to enhance immune activity in these cells. The aim of this study was to investigate the immunological effects of taurolidine and correlate findings with survival after a septic challenge in a murine model. Study 1: CD-1 mice underwent cecal ligation and puncture, were randomized to receive taurolidine (200 mg/kg body weight/i.p.) or saline control, and studied for end point survival. Study 2: CD-1 mice were randomized to receive taurolidine (200 mg/kg body weight/i.p.) or saline control. Peritoneal macrophages (PM luminal diameters) were assessed for O2-, NO, tumor necrosis factor-alpha (TNF-alpha), CD11b, phagocytosis, and PMN influx. O2-, TNF-alpha, CD11b expression, and phagocytosis were significantly increased in the taurolidine group. Study 3: PM luminal diameters were cultured in vitro +/- 0.5 mg/ml taurolidine and PM luminal diameter antimicrobial function assessed (O2-, NO, TNF-alpha, and phagocytosis). O2-, TNF-alpha, and phagocytosis were significantly increased, whereas NO was reduced. Study 4: PM luminal diameters were also cultured with taurine (0.5 mg/ml). Similar increase in O2-, TNF-alpha, and phagocytosis were identified. Intracellular PM luminal diameter [Ca2+] was also assessed and increases in free, unbound intracellular [Ca2+] occurred after taurine culture. Thus, in addition to its bactericidal and antilipopolysaccharide activity, taurolidine primes PM luminal diameters for enhanced antimicrobial activity and these effects appear mediated by the amino acid taurine.

Animals↗

The beneficial effects of immunostimulation in posttraumatic sepsis.

Granulocyte macrophage-colony stimulating factor (GM-CSF) is a myelopoietic cytokine that may enhance immune mechanisms directed against bacterial infection. Injury is associated with an increased incidence of such infection. This study assessed the potential immunostimulatory role of GM-CSF in the injured host predisposed to infection. Six- to eight-week old female CD-1 mice underwent trauma and were then randomized to received either GM-CSF or saline vehicle control intraperitoneally for 5 days. They then received a septic challenge in the form of a cecal ligation and puncture. Following this, assessment was made of survival and bacterial growth indices in blood cultures, and peritoneal cells were harvested for assessment of peritoneal immune function. Intraperitoneal GM-CSF administration daily for 5 days following injury was associated with significantly greater survival following cecal ligation and puncture compared to controls (40 vs 5%, P < 0.05). There was a significant increase in peritoneal cell yields in the GM-CSF group compared to the control group (11 +/- 1 x 10(6) vs 8 +/- 1 x 10(6) P < 0.05). PMA-stimulated macrophages released significantly higher amounts of both superoxide anion (1.4 +/- 0.1 vs 0.93 +/- 0.1, P < 0.05) and tumor necrosis factor (5.2 +/- 0.6 vs 2.6 +/- 0.7, P < 0.03) and significantly less nitric oxide compared to the control group (175 +/- 8 vs 267 +/- 24, P < 0.003). Finally, bacterial growth indices were significantly reduced following GM-CSF administration (194 +/- 6 vs 218 +/- 4, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Laparoscopic left adrenalectomy: a new approach.

Left adrenalectomy has been performed previously via anterior, posterior, loin or thoracoabdominal approaches. In the classical transabdominal approach the left adrenal gland is resected following either mobilization of the spleen with the tail of the pancreas or after entering the lesser sac, mobilizing the inferior border of the pancreas off the adrenal gland. This report describes laparoscopic left adrenalectomy, in a patient with Conn's syndrome, performed by a new approach via the root of the left transverse mesocolon.

Adrenalectomy↗

Role of lipopolysaccharide and tumor necrosis factor-alpha in induction of hepatocyte necrosis.

The occurrence of acute hepatic failure during systemic inflammatory response syndrome (SIRS) is related to the extent of hepatocyte (HC) damage and cell death resulting from necrosis or apoptosis. We hypothesized that proinflammatory mediators such as lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) can, either directly or indirectly through neutrophil (PMN) and Kupffer cell (KC) activation, induce HC damage and cell death, and that the mechanism is cellular necrosis rather than apoptosis. The results in this study demonstrated that LPS and TNF-alpha alone and in combination are directly cytotoxic to cultured rat HC as indicated by the hepatocellular enzyme release and HC necrosis. However, LPS and TNF-alpha, in the presence of sodium arsenite (a heat shock inducer), were unable to induce HC apoptosis. Both KC and PMN activated by either LPS or TNF-alpha induced significant hepatocellular enzyme release and HC necrosis, which was dependent on the ratio of KC and PMN to HC. It is concluded that LPS and TNF-alpha may play a central role in the development of acute hepatic failure after severe trauma and sepsis by directly or indirectly inducing HC necrosis rather than apoptosis.

Animals↗

Elevated levels of lipoprotein (a) in association with cerebrovascular saccular aneurysmal disease.

The relationship between cerebrovascular aneurysmal disease and atherosclerosis remains unclear. Elevated serum levels of lipoprotein (a) (Lp[a]), are an independent risk factor for atherosclerosis. We measured serum Lp(a) levels in 50 patients who had angiographically proven saccular aneurysmal disease and who were free of clinically significant atheromatous disease (as judged by their medical histories and the results of physical examination, electrocardiography, and carotid angiography). The Lp(a) serum levels in these patients were compared with the Lp(a) serum levels in a group of 42 normal healthy controls. Serum Lp(a) levels in the patients was 20.1 +/- 0.42 mg/dl (median +/- standard error); however, median serum Lp(a) in the control subjects was 10.8 +/- 0.47 mg/dl (P < 0.01). Among females, the difference in serum Lp(a) levels was significant; the levels were 22.2 +/- 0.6 for female patients (n = 29) and 9.5 +/- 0.53 in female control subjects (n = 26) (P < 0.005). The most significant difference (P < 0.002) was seen in females < 50 years old (14 patients, 10 control subjects). No significant differences were seen in the Lp(a) serum levels between 21 male patients and 16 male control subjects. Lp(a) levels above the threshold level (30 mg/dl) were found in 20 patients and 7 control subjects (chi 2 = 5.99, P < 0.02); 12 female patients and 3 female control subjects (chi 2 = 6.16, P < 0.02; 8 male patients and 4 male control subjects (this difference was not significant). These results indicate either that cerebrovascular aneurysmal disease and subclinical atherosclerosis are related or that Lp(a) is a risk factor for vasculopathies other than atheroma.

Adult↗

Normal inspiratory muscle strength is restored more rapidly after laparoscopic cholecystectomy.

Respiratory complications after laparotomy cholecystectomy may result from generalised muscle weakness and fatigue, or from reduced respiratory muscle function secondary to an upper abdominal incision. In a prospective study we compared maximal inspiratory effort (Pimax/mmHg) and dominant hand grip strength (kPa) (expressed as a percentage of zero hour value) in patients undergoing open cholecystectomy (OC) (n = 12), laparoscopic cholecystectomy (LC) (n = 25) and a control group of patients undergoing lower limb surgery (n = 12). Of the 12 OC patients, three suffered respiratory complications: two had atelectasis and one a chest infection, compared with no such complications in the other two groups (P < 0.05). Pimax decreased postoperatively in all groups (P < 0.05) and had returned to normal by 48 h in the LC and control groups. In contrast, in the OC group Pimax fell from 112.5 +/- 17.8 mmHg to as low as 81.3 +/- 16.5 mmHg at 72 h and only returned to preoperative levels at 120 h. The hand grip strength fell significantly in all groups at 24 h (P < 0.05) but normal levels were achieved again by 48 h in all groups, and there was no significant difference in the hand grip strength between the groups over the 5 days. These results suggest that generalised muscle fatigue after surgery is similar after open and laparoscopic cholecystectomy. Open cholecystectomy does, however, cause a more prolonged reduction in respiratory muscle function and this is likely to contribute to the higher incidence of respiratory complications in this group of patients.

Adult↗

Hernia repair.

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Adult↗

Immune function in patients undergoing open vs laparoscopic cholecystectomy.

BACKGROUND: Abnormal release of inflammatory mediators following surgical injury is associated with immunological alteration, which may predispose to sepsis. Laparoscopic surgery is associated with reduced postoperative complications, but mechanisms are unclear. We hypothesized that early recovery following laparoscopic surgery may relate to minimal impairment of immune function. DESIGN: Analysis of the temporal immune responses in two similar groups of patients randomized to open (n = 22) vs laparoscopic (n = 22) cholecystectomy. Patients were matched for age, height, weight, and operation time. Immune parameters, including monocyte superoxide anion (O2-) and tumor necrosis factor release, neutrophil O2- levels and chemotaxis, total white blood cell counts, partial arterial oxygen pressure, and serum cortisol and C-reactive protein levels were assessed preoperatively and on postoperative days 1 and 3. RESULTS: There were significant increases (P < .001) in monocyte release of O2- and tumor necrosis factor, neutrophil release of O2- and chemotaxis, and white blood cell count in the open vs laparoscopic cholecystectomy study groups, with a concommitant decrease in partial arterial oxygen pressure. These findings correlated with significantly higher postoperative septic complications in the open cholecystectomy group (P < .05). There were no significant differences in either plasma cortisol or C-reactive protein levels between groups. All measurements were carried out in a blinded fashion. CONCLUSIONS: This study demonstrates that laparoscopic surgery appears to be associated with similar metabolic responses compared with open surgery, while immune parameters vary greatly between groups. The beneficial effects of laparoscopic surgery may relate, in part, to preservation of immune function in the postoperative period.

Adult↗

Postoperative immunological function and jaundice.

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

Animals↗

Role of endotoxin in mononuclear phagocyte-mediated inflammatory responses.

Lipopolysaccharide (LPS), which is derived from the cell wall of gram-negative and some gram-positive bacteria, plays a major role is the pathogenesis of septic shock. Initiation of these responses depends on LPS interaction with a number of immune cells, not least the mononuclear phagocyte (MP). Mononuclear phagocytes bind the LPS/lipopolysaccharide-binding protein complex through the CD14 receptor and thus mediate the release of a wide range of inflammatory mediators. Release of these mediators is teleologically beneficial but under certain circumstances may be detrimental, resulting in the systemic inflammatory response syndrome. The development of this syndrome is not clearly understood but appears, in part, to be dependent on the ability of the host to respond to these mediators. This review evaluates the mechanisms of LPS-MP interaction and the therapeutic strategies aimed at inhibiting this interaction.

Animals↗

Nitric oxide (endothelium-derived relaxing factor) attenuates revascularization-induced lung injury.

Aortic occlusion and revascularization (I-R) may lead to lung injury dependent on activated neutrophil adherence. Nitric oxide (NO) inhibits neutrophil adherence to endothelial cells. We studied the effect of increasing or decreasing NO levels with sodium nitroprusside (SNP) or N-nitro-L-arginine methyl ester (L-NAME) in an I-R lung injury model of 30 min ischemia followed by 120 min reperfusion. Sprague-Dawley rats (10/group) were randomized to controls, I-R, I-R treated with L-NAME (10 mg/ml/hr), and I-R treated with SNP (0.2 mg/ml/hr). Myeloperoxidase activity (MPO) was used as a measure of pulmonary neutrophil influx. Pulmonary endothelial permeability was measured by wet:dry weight ratio and bronchoalveolar lavage protein (BAL prot) and neutrophil counts (BAL PMN). Aortic occlusion and revascularization led to significant increases in pulmonary neutrophil influx (6.1 +/- 0.1 MPO u/g vs 3.05 +/- 0.4 MPO u/g in the control group, P < 0.001) and microvascular leakage; BAL prot (347 +/- 32 mg/ml in controls vs 454 +/- 16 mg/ml in the I-R group, P < 0.05); and BAL PMN (0.7 +/- 0.05 in controls vs 1.8 +/- 0.07 PMN/ml in the I-R group, P < 0.001). These changes were exacerbated further by administration of L-NAME (MPO = 8.9 +/- 0.7; BAL prot = 581 +/- 40 mg/ml; BAL PMN = 2.7 +/- 0.16 PMN/ml). Sodium nitroprusside therapy attenuated the I-R-induced lung injury (3.5 +/- 0.4 MPO u/g, P < 0.05 vs I-R; BAL prot = 330 +/- 61 mg/ml; BAL PMN = 0.9 +/- 0.1 PMN/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The need to retrieve the dropped stone during laparoscopic cholecystectomy.

The effect of bile and gallstones on the peritoneal cavity was evaluated in an experimental animal study. Ninety male Sprague-Dawley rats were randomly allocated to one of six groups (n = 15). Groups 1 to 3 received an intraperitoneal injection (2 mL) of saline, sterile bile, and infected bile, respectively. Groups 4 to 6 underwent a lower midline abdominal incision (3 to 5 mm). In groups 4 and 5, a single gallstone (< 3 mm diameter) was placed in the right upper quadrant and, after closure of the wound, the animals were injected with sterile bile and infected bile, respectively. Group 6 animals underwent laparotomy alone, followed by injection of sterile saline (2 mm). All animals were killed at 4 weeks and the peritoneal cavity was carefully examined. No intra-abdominal lesions were noted in groups 1 to 3. Adhesions were noted in 11 (73%) and 10 (67%) animals of groups 4 and 5, respectively. Two intra-abdominal abscesses were noted in group 4 animals. No intra-abdominal lesions were noted in any group 6 animals. This study suggests that bile in combination with gallstones in the peritoneal cavity is associated with an increased risk of intra-abdominal adhesion formation and possible abscess formation, and that every attempt should be made to retrieve stones lost during cholecystectomy.

Animals↗

Biochemical and molecular genetic studies of abdominal aortic aneurysm in an Irish population.

Abdominal aortic aneurysm (AAA) is a common disease of the elderly exhibiting a complex aetiology. In a survey of 82 Irish aneurysm patients, compared to 79 age- and sex-matched control subjects, we have investigated a number of potential biochemical and molecular genetic markers which are amenable to analysis from blood specimens and which might have predictive value for AAA. No significant differences were observed between patients and control subjects in relation to serum lipids, leucocyte elastase activity or serum alpha 1-antitrypsin concentration. We have used the polymerase chain reaction to screen the patient and control groups in search of disease-associated genetic variation on chromosome 16, particularly in the region of the Cholesteryl Ester Transfer Protein (CETP) gene. Although variation in allele frequencies was detected between patients and controls at the four marker loci studied, no significant gene-disease associations were detected. The absence of gene-disease associations in our study may indicate that the genetic component in the aetiology of AAA in Ireland differs from that in the UK. Alternatively, it may indicate that the high degree of polymorphism at microsatellite loci may make them unsuitable as markers for the study of gene-disease associations in moderately sized populations. We therefore conclude that the biochemical and molecular genetic markers which we have examined are of no predictive value, and that ultrasonography remains the screening modality of choice for abdominal aortic aneurysm.

Aged↗

Ankle fracture is associated with prolonged venous dysfunction.

Leg swelling is a significant problem following ankle fracture. Venous pump function and femoral and popliteal venous patency were assessed prospectively in 26 patients with ankle fractures requiring open reduction, internal fixation and immobilization in plaster. Functional venous volume, venous filling index (VFI), ejection volume fraction (EVF) and residual volume fraction (RVF) were measured using air plethysmography at 5 days and at 6, 12 and 18 weeks after fracture. The uninjured leg was used as a control. Popliteal and femoral venous patency was determined using duplex ultrasonography. No patient developed deep vein thrombosis during the study. At 5 days after fracture there was a significant reduction in mean(s.d.) EVF, 18.2(12.1) versus 55.9(19.5) per cent, and increase in RVF, 87.0(14.3) versus 42.5(22.2) per cent (both P < 0.001). Analogous values were similar at 6 weeks, EVF 28.5(21.2) versus 55.6(21.9) per cent, RVF 82.2(16.8) versus 48.5(23.8) per cent (both P < 0.001), and at 12 weeks, EVF 39.1(16.0) versus 60.3(14.9) per cent, RVF 64.7(18.8) versus 38.8(13.2) per cent (both P < 0.001). However, by 18 weeks there was no significant difference in venous function between fractured and control limbs. It is concluded that there is a significant and prolonged impairment in venous pump function following ankle fracture.

Ankle Injuries↗

Selective cholangiography in laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is now the method of choice for removing the diseased gallbladder. Asymptomatic common bile duct stones occur in approximately 6 per cent of patients. Controversy exists, however, as to whether selective or routine peroperative cholangiography should be performed during laparoscopic cholecystectomy. Over a 21-month period 300 consecutive laparoscopic cholecystectomies without routine cholangiography were attempted. There were 28 conversions. In all, 229 patients did not undergo cholangiography and in this group there were two common duct injuries. These were both identified and dealt with by open operation. Five patients underwent peroperative cholangiography, none of whom was found to have common duct pathology. Endoscopic retrograde cholangiopancreatography was performed in 38 patients. Of 27 who had this investigation performed before operation, common duct stones were diagnosed in seven (26 per cent). Two common duct stones were discovered in 11 patients who underwent the investigation after operation. Thus only two of 240 patients (0.8 per cent) who did not undergo preoperative or peroperative cholangiography subsequently had symptomatic duct stones. Peroperative cholangiography may be indicated in selected patients who have had symptoms of common bile duct stones or in those in whom the biliary anatomy is unclear. However, routine preoperative or peroperative cholangiography is unnecessary during laparoscopic cholecystectomy.

Adolescent↗