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Biomedical subjects

D Bouchier-Hayes

Publications and source records attributed to D Bouchier-Hayes.

At least 55 records · Page 3Linked to original sources
PubMed1999

Neutrophil heat shock protein expression and activation correlate with increased apoptosis following transmigration through the endothelial barrier.

Polymorphonuclear leukocytes (PMN) undergo endothelial transmigration upon activation or in response to a chemoattractant. Such cells are stressed and have an increased capacity to incite tissue injury. Little is known about the effect of transmigration on PMN stress gene responses, PMN activation, and ultimately programmed cell death (apoptosis). Human endothelial cells (ECV-304) were plated onto transwell membranes to form an endothelial monolayer and PMN transendothelial migration through this endothelial barrier was examined. Chemotaxis was induced by formyl-methionyl-leucyl-phenylalanine (fMLP). Flow cytometry was used to determine PMN receptor expression (CD11b, CD14, CD16, CD18, CD54), phagocytosis, and apoptosis. Heat shock protein (Hsp) expression was evaluated by Western blotting. fMLP-induced PMN transendothelial migration resulted in increased adhesion receptor expression and phagocytosis. Migrated PMN also had an increased rate of apoptosis as evaluated by uptake of propidium iodide and decreased FcgammaR III (CD16) expression. Increased PMN apoptosis coincided with induction of Hsp72 following transmigration. Thus, naive PMN that migrate through endothelium in response to a chemoattractant undergo activation as represented by increased phagocytosis and expression of adhesion receptors.

Antigens, CD↗
PubMed1999

Taurine prevents high-glucose-induced human vascular endothelial cell apoptosis.

Elevated blood glucose in uncontrolled diabetes is causally correlated with diabetic microangiopathy. Hyperglycemia-triggered accelerated endothelial cell apoptosis is a critical event in the process of diabetes-associated microvascular disease. The conditionally semiessential amino acid taurine has been previously shown to protect against human endothelial cell apoptosis. Therefore, this study was designed to investigate the role of taurine in the prevention of high-glucose-mediated cell apoptosis in human umbilical vein endothelial cells (HUVEC) and the mechanisms involved. Exposure of HUVEC to 30 mM glucose for 48 h (short-term) and 14 days (long-term) resulted in a significant increase in apoptosis, compared with normal glucose (5.5 mM; P < 0.05). High-glucose-induced DNA fragmentation preferentially occurred in the S phase cells. Mannitol (as osmotic control) at 30 mM failed to induce HUVEC apoptosis. Taurine prevented high-glucose-induced HUVEC apoptosis, which correlates with taurine attenuation of high-glucose-mediated increased intracellular reactive oxygen species (ROS) formation and elevated intracellular Ca(2+) concentration ([Ca(2+)](i)) level. Antioxidants, DMSO, N-acetyl cysteine, and glutathione, only partly attenuated high-glucose-induced HUVEC apoptosis. Glucose at 30 mM did not cause HUVEC necrosis. However, both glucose and mannitol at 60 mM caused HUVEC necrosis as represented by increased lactate dehydrogenase release and cell lysis. Taurine failed to prevent hyperosmolarity-induced cell necrosis. These results demonstrate that taurine attenuates hyperglycemia-induced HUVEC apoptosis through ROS inhibition and [Ca(2+)](i) stabilization and suggest that taurine may exert a beneficial effect in preventing diabetes-associated microangiopathy.

Antioxidants↗
PubMed1999

Phenotyping of immune cell infiltrates in breast and colorectal tumours.

White cell infiltration of solid tumors is an important prognostic indicator in malignant disease. Although macrophage infiltration is associated with good outcome in colorectal cancer, a high macrophage content is associated with poor prognosis in breast cancer. Suppressor macrophages prevent T cell activation in normal tissues such as mucosal linings exposed to continuous antigenic challenge. Interleukin 10 (IL-10), an immunosuppressive cytokine, inhibits macrophage co-stimulation of T cells. Suppressor macrophage numbers, T cell numbers and T cell activation status were assessed in cell suspensions obtained from fresh specimens of breast and colorectal tumours and matched normal tissues. IL-10 production by both malignant and matched normal tissue was also assessed. This study identified elevated numbers of suppressor macrophages in breast tumors compared to matched normal breast tissue. Colorectal tumors did not contain significant numbers of these cells. Although T cell numbers are increased in breast tumors, these cells do not appear to be fully activated, as assessed by major histocompatibility complex class II and Interleukin 2 receptor expression. In contrast, T cells in colorectal tumors exhibit greater expression levels of these markers. Breast tumors produce significantly higher levels of IL-10 than normal breast tissue whereas IL-10 levels in colorectal tumors are similar to normal colon tissue. Our findings of high suppressor macrophage numbers, high levels of IL-10 and poorly activated T cells in breast tumors compared to low suppressor macrophage numbers, low IL-10 and fully activated T cells in colorectal tumors may explain why high macrophage content is associated with poor prognosis in breast cancer and good prognosis in colorectal malignancy.

Adult↗
PubMed1999

Inhibition of neutrophil apoptosis after elective surgery.

BACKGROUND: Neutrophils play a crucial role in host defense against infections, but their inappropriate infiltration and activation within tissues can cause host tissue damage through release of reactive oxygen metabolites, metalloproteinases, and proinflammatory cytokines. The termination of a neutrophil-mediated inflammatory response is effected through programmed cell death or apoptosis. Delayed neutrophil apoptosis is associated with proinflammatory diseases, such as the systemic inflammatory response syndrome. Surgery induces a profound inflammatory response; therefore, neutrophil apoptosis of patients undergoing elective surgery was investigated. METHODS: Nonseptic patients undergoing elective orthopedic surgery while under epidural anesthesia had neutrophils and platelet-poor isolated from whole venous blood harvested at 4 time points: pre-epidural, 45 minutes postepidural but before surgical intervention, 1 hour postsurgical incision, and 24 hours postsurgery. Neutrophil apoptosis was quantified at 1, 12, and 24 hours in culture by immunofluorescence flow cytometry of annexin V and propidium iodide staining and confirmed by TUNEL (terminal deoxynucleotidyl transferase nick end labeling) assay for DNA strand breaks. Serum cytokines were quantified by specific enzyme-linked immunosorbent assay. RESULTS: Spontaneous neutrophil apoptosis after elective surgery was significantly (P < .001) inhibited with an effect evident within an hour of surgical incision and persisting at 24 hours postsurgery. The addition of patients' 24 hour postoperative plasma to healthy neutrophils markedly (P < .01) reduced neutrophil apoptosis, whereas plasma taken an hour after surgical incision was ineffective. Interleukin (IL)-6 was notably increased (1395 +/- 196 pg/mL, P < .01) 24 hours postsurgery and at this postoperative concentration inhibited (P < .01) apoptosis of normal neutrophils. Levels of other inflammatory mediators (IL-1 beta, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, soluble Fas, soluble Fas ligand) were unaltered. The anti-inflammatory cytokine IL-10 was only slightly increased 24 hours postsurgery (8.32 +/- 2.99 pg/mL); however, the addition of recombinant human IL-10 (10 ng/mL) counteracted (P < .05) inhibition of neutrophil apoptosis induced by IL-6 and post-surgery plasma. CONCLUSIONS: These results identify marked inhibition of neutrophil apoptosis after elective surgery and suggest that the inhibition of neutrophil apoptosis in the postoperative period is, at least in part, a result of soluble circulating factors. The marked imbalance favoring proinflammatory over anti-inflammatory cytokine release in the immediate postoperative period mediates the overwhelmingly antiapoptotic net capacity of postsurgery plasma.

Aged↗
PubMed1998

Extraspinal causes of sciatica. A case report.

STUDY DESIGN: A case of intrapelvic aneurysm is reported. It is as an example of one of the many extraspinal causes of sciatica. OBJECTIVE: To demonstrate the importance of clinical examination in the assessment of patients with sciatic, despite continuing improvements in methods for imaging the spine. SUMMARY OF BACKGROUND DATA: Extraspinal conditions cause sciatic in a rare but recognized group of patients. Their clinical symptoms can be very similar to those of patients with sciatic from lumbar disc protrusion. METHODS: The clinical appearance, investigation, and treatment of a patient with an internal iliac artery aneurysm causing sciatic are discussed. RESULTS: Surgical treatment of the patient's aneurysm resulted in relief of the symptoms of sciatica. CONCLUSIONS: Although these cases are unusual in isolation, together they represent an important group. When a patient has sciatica, the clinician looks first to the spine for the origin of symptoms. Extraspinal causes are often not considered in the differential diagnosis. This oversight may be compounded by observation of asymptomatic disc protrusions on computed tomographic and magnetic resonance studies. The importance of clinical history and examination in the diagnosis of these lesions cannot be overemphasized.

Aneurysm↗
PubMed1998

Effects of human recombinant growth hormone (rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.

BACKGROUND: Human recombinant growth hormone (rhGH) has been shown to increase skeletal muscle protein synthesis and improve nitrogen balance in critically ill patients and those undergoing surgery. rhGH effects on hepatic protein turnover in critically ill patients are less clearly understood. OBJECTIVE: To examine rhGH effects on hepatic acute phase protein responses and inflammatory cytokine release in patients undergoing major surgery. DESIGN: Prospective double blind randomised trial. SETTING: Tertiary referral university teaching hospital. PATIENTS: Patients undergoing elective abdominal aortic aneurysm repair. INTERVENTION: Patients received rhGH (Genotropin, 0.3 IU/kg per day, n = 8) or placebo (n = 10) for 6 days prior to surgery. RESULTS: Blood levels of growth hormone (GH) and insulin-like growth factor (IGF-1) were measured following rhGH treatment and C-reactive protein (CRP), serum amyloid A (SAA) and the cytokines interleukin-6 (IL-6) and the IL-1 receptor antagonist (IL-1ra) were measured for up to 24 h following surgery. Significant increases in plasma rhGH (0.84 +/- 0.3, mean (sem) versus 52 +/- 20 mU/l, p < 0.0008) and IGF-1 levels (119 +/- 13 versus 644 +/- 110 ng/ml, p < 0.0001) were seen prior to surgery following rhGH administration. No differences in acute phase protein or cytokine levels were seen following surgery in patients receiving rhGH. CONCLUSIONS: These results indicate that pre-operative administration of rhGH does not alter acute phase protein or inflammatory cytokine release in response to major surgery.

Aged↗
PubMed1998

Laparotomy and laparoscopy differentially accelerate experimental flank tumour growth.

BACKGROUND: Surgery depresses host tumoricidal activity and may increase tumour growth. This study compared the effects of laparoscopy with laparotomy on extraperitoneal tumour growth and immune function in a murine model. METHODS: C57BL/6 female mice aged 8-10 weeks had tumours induced in the right flank (n=45) and were randomized to undergo halothane anaesthesia only, laparoscopy or laparotomy. Flank tumour volume was assessed over 10 days. A second group of animals (n=540) were randomized to undergo the same procedures and killed at 24, 48 and 96 h. Splenocytes were harvested for natural killer (NK) cell and lymphokine activated killer (LAK) cell cytotoxicity studies. RESULTS: There was a significant increase in flank tumour growth in the first 48 h after laparotomy and laparoscopy compared with controls (P < 0.01). By 96 h the difference was only significant in the laparotomy group (P< 0.01). Both NK and LAK cell cytotoxicities were suppressed significantly (P < or = 0.03) from 24 h up to 96 h following laparotomy compared with control and laparoscopy groups. There was also a significant suppression in the laparoscopy group compared with controls in the first 48 h after operation (P < or = 0.02). CONCLUSION: Extraperitoneal tumour growth was significantly accelerated after laparotomy and correlated with significantly suppressed NK and LAK cytotoxicity for at least 4 days after operation. Laparoscopy had a shorter, less profound effect on tumour growth and immune function.

Animals↗
PubMed1998

Nitric oxide mediates hepatocyte injury.

The degree of acute hepatic failure after severe trauma and sepsis is related to the extent of hepatocyte (HC) damage and cell death resulting from either necrosis or apoptosis. We have previously demonstrated that tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS) can directly lead to HC necrosis, but not apoptosis. To date, the reactive oxygen intermediates (ROI) and nitric oxide (NO) have been shown to play a potential role in the induction of cell apoptosis. However, it is unknown whether ROI and NO are involved in HC cell death. Therefore, in this study we tested the hypothesis that NO and ROI exert different effects on HC cell death. TNF-alpha and LPS alone failed to induce HC apoptosis but when combined with antioxidants resulted in HC apoptosis and DNA fragmentation, which is correlated with an increase in NO production. This effect was attenuated by the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). Moreover, the NO donor sodium nitroprusside resulted in HC apoptosis and cell damage as represented by hepatocellular enzyme release. Antioxidants inhibited TNF-alpha- and LPS-mediated ROI generation and peroxynitrite formation in HC. TNF-alpha- and LPS-induced HC damage could be further reduced by the combination of antioxidants and L-NMMA. These results indicate that NO is involved in HC injury, primarily through the induction of HC apoptosis.

Animals↗
PubMed1998

Diphenylhydantoin sodium promotes early and marked angiogenesis and results in increased collagen deposition and tensile strength in healing wounds.

BACKGROUND: Sodium diphenylhydantoin (DpH) (phenytoin) was first introduced as an antiepileptic in 1938. One of its side effects, gingival hyperplasia, prompted investigation into the possible application of this drug as a promoter of wound healing. Since the late 1950s phenytoin has been used in a variety of clinical situations. However, its exact mechanism of action is still debated. The aim of this study was to determine the effect of DpH on wound healing in an incisional rat model. METHODS: A four dorsal wound model was used, and each cephalad wound had a polyvinyl alcohol sponge placed in a subcutaneous pocket just above its cephalad end. Caudal and cephalad wounds were treated with 10 mg DpH in 200 microliters carrier, and the other two wounds received an equal volume of the saline vehicle as controls on the day of wounding and on the third and sixth postoperative days. The animals were killed on the tenth postwounding day. Tensile strength of fresh and fixed scars was determined using constant speed tensiometry, and wound hydroxyproline was determined spectophotometrically. RESULTS: There was a highly significant increase in both fresh and fixed wound tensile strength of all DpH-treated wounds compared with controls (p < 0.001). This was reflected by a significant increase in polyvinyl alcohol sponge hydroxyproline in DpH-treated wounds compared with saline-treated wounds (p = 0.002). Histologic examination of these wounds was performed at 3 and 6 days after wounding. There was moderate fibroblast infiltration with a marked inflammatory infiltrate and neovascularization in the DpH-treated wounds compared with controls at 3 days. By day 6, the inflammatory infiltrate had almost totally receded in the treated wounds, but fibroblast infiltration and angiogenesis were still persistently marked. In comparison, the saline-treated wounds still had moderate inflammatory and fibroblast infiltrate and mild angiogenesis. CONCLUSIONS: DpH alters the natural course of wound healing and may be of benefit in clinical situations where defective wound collagen deposition may lead to poor wound healing and consequent morbidity and mortality.

Animals↗
PubMed1998

The patients' perception of quality in surgery.

The benefits of measuring patient satisfaction have been increasingly acknowledged in recent years. A range of techniques has been used including analysis of complaints made by patients and/or relatives, focus group interviews following discharge, postal and telephone surveys, face-to-face interviews and critical incident analysis. Both quantitative and qualitative methodologies are often employed in patient-satisfaction research. It is suggested that a two-tier approach of methods can increase validity and reliability (i.e. utilizing qualitative approaches in order to develop a quantitative tool). Surgery will benefit through the identification of quality benchmarks based on this type of research. There must be an emphasis on incorporating the results of patient satisfaction studies into practice and the monitoring of improvements based on the identified benchmarks.

Attitude to Health↗
PubMed1997

Induction of heat shock protein 72kDa expression is associated with attenuation of ischaemia-reperfusion induced microvascular injury.

Leukocyte-endothelial interaction is a pivotal step in the pathogenesis of ischemia-reperfusion (I/R) injury. Exposure of cells to a subcritical heat stress may protect cells from subsequent I/R injury, through induction of a 72-kDa heat shock protein (HSP72). The aim of this study was to investigate the effect of thermotolerance on leukocyte adherence and migration during an I/R period in rat mesenteric postcapillary venules. Sprague-Dawley rats were randomized into control (sham I/R), I/R, and thermotolerance+I/R groups. Thermotolerance was induced 18 hr prior to I/R, which was in turn established by occlusion of the superior mesenteric vascular pedicle for 10 mins, followed by 60 mins of reperfusion. The blood flow, leukocyte rolling velocity, and the number of adherent and migrated leukocytes in postcapillary venules were measured by intravital microscopy. I/R significantly decreased the rolling velocity of leukocytes; increased the number of adherent leukocytes at 10, 30, and 60 mins after reperfusion; and also increased the number of migrated leukocytes at 60 mins after reperfusion. Thermotolerance induction expression of HSP72 in pulmonary, intestinal, and mesenteric tissues was determined by Western immunoblotting. Thermotolerance significantly prevented the I/R-induced decrease in rolling velocity of leukocytes, the increase in the number of adherent leukocytes at 30 and 60 mins, and the increase in the number of migrated leukocytes at 60 mins. This results suggest that thermotolerance attenuates I/R injury by modulating leukocyte-endothelial interaction in vivo, possibly by increasing tissue expression of HSP72.

Animals↗
PubMed1997

Dexamethasone and lipopolysaccharide regulation of taurine transport in Caco-2 cells.

Intracellular enterocytic levels of the immunomodulator taurine decrease significantly in response to trauma and surgical insult. The effect of physiological stress on enterocyte taurine uptake is unknown. The aim of this study was to compare taurine transport under basal and stressed conditions using the human intestinal Caco-2 cell line in vitro. Caco-2 cells were incubated with 10 nM [1,2-3H]taurine at 37 degrees C and 5% CO2 and taurine uptake was examined over the range of 0.1-10 microM to determine kinetic parameters of the transporter. The culture medium was then supplemented with dexamethasone and/or lipopolysaccharide (LPS) and taurine uptake was calculated as picomoles per milligram protein per hour. Statistics were by unpaired Student's t test. Taurine uptake was hyperbolically related to taurine concentration and obeyed Michaelis-Menten kinetics with a K(m) of 5.27 +/- 0.95 microM and Vmax of 1125.43 +/- 130.9 pmole/mg protein/ hour. Dexamethasone (1-1000 microM) significantly reduced taurine uptake by up to 66.15%. LPS (1 microgram/ml) impaired transport of taurine by 15.7%, and in combination with dexamethasone (100 microM) by 42.4%. All results are mean of at least three experiments and P < 0.05. We have established that taurine uptake by enterocytes is downregulated by dexamethasone. This may relate to the decreased intestinal levels of taurine observed in trauma and surgery patients. Further study may elucidate mechanisms whereby homeostasis of enterocyte taurine might be maintained during sepsis.

Biological Transport↗
PubMed1997

Carcinoid disease: review of the literature.

Carcinoid syndrome is the product of a rare but fascinating malignant neoplasm. Carcinoid syndrome was described more than 100 years ago, and recent advances in diagnostic localization, elucidation of the mechanisms of oncogenesis, treatment options, and, consequently, patient prognosis have been made. Current modalities of treatment, possible therapeutic implications of new avenues of research, and current literature on the chemotherapeutic combinations used are reviewed.

Carcinoid Tumor↗
PubMed1997

Lipoprotein (a): a potential biological marker for unruptured intracranial aneurysms.

OBJECTIVE: The diagnosis and treatment of intracranial aneurysms (IAs) prior to rupture reduces the high morbidity and mortality associated with their occurrence. Elevated serum lipoprotein (a) [Lp(a)] level, an independent risk factor for atherogenesis, has been demonstrated in sporadic IA disease (1). The purpose of this study was to assess the degree of correlation between elevated Lp(a) levels and the occurrence of IAs in asymptomatic first degree relatives of index cases from three families exhibiting a familial tendency towards IA development. METHODS: 25 family members and 41 healthy controls were screened by random serum Lp(a) sampling. All family members received 4-vessel cerebral angiography. RESULTS: Eleven family members were found on angiography to harbour asymptomatic aneurysms and all were successfully treated by surgery. Of these 11, ten had significantly raised serum Lp(a) levels (> 30 mg%). Fourteen family members had negative angiograms. Eight of this latter group, mean age 43.6 +/- 3.8 years, had serum Lp(a) levels above the normal range. Mean Lp(a) levels were 53.7 +/- 1.2 mg% in subjects with aneurysms compared with 22.1 +/- 1.45 mg% in subjects without demonstrable aneurysms and 10.5 +/- 0.48 mg% in the control population. CONCLUSION: The prevalence of elevated Lp(a) levels in these families and the high degree of association of raised Lp(a) levels with the presence of IAs in several family members warrants follow up of angiographically negative young subjects. We require a case-control study to establish whether particular polymorphisms at the apoprotein (a) gene level are associated with the occurrence of IAs in these families.

Adult↗
PubMed1997

Intercellular adhesion molecule-1 (ICAM-1) is expressed on human neutrophils and is essential for neutrophil adherence and aggregation.

This study investigated the expression and regulation of intercellular adhesion molecule-1 (ICAM-1) on human polymorphonuclear neutrophils (PMNs), and its potential role in PMN-PMN adherence and aggregation as observed during systemic inflammatory response syndrome. Normal human PMNs were found to express ICAM-1 with 90% positive population, and this expression was augmented by endotoxin (lipopolysaccharide, LPS) and tumor necrosis factor-alpha (TNF-alpha) stimulation. The presence of ICAM-1 mRNA in human PMNs was further detected by reverse transcription-polymerase chain reaction before and after LPS and TNF-alpha treatment. Furthermore, incubation of PMNs with LPS and TNF-alpha resulted in significant increases in PMN-PMN adherence and aggregation, while addition of either anti ICAM-1 mAb or anti CD11b/CD18 mAb significantly inhibited LPS and TNF-alpha-mediated PMN-PMN adherence and aggregation. These novel findings demonstrate that ICAM-1 is expressed on human PMNs and responsible for PMN aggregation, and suggest that the interaction between ICAM-1 and CD11b/CD18 may be the molecular basis for PMN aggregation and clumping in the microcirculation during systemic inflammatory response syndrome.

Adult↗