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Biomedical subjects

N F Fanning

Publications and source records attributed to N F Fanning.

7 recordsLinked to original sources
PubMed1999

Circulating granulocyte macrophage colony-stimulating factor in plasma of patients with the systemic inflammatory response syndrome delays neutrophil apoptosis through inhibition of spontaneous reactive oxygen species generation.

In the normal resolution of an acute inflammatory response apoptosis of neutrophils is essential to maintain immune homeostasis and limit inappropriate host tissue damage by decreasing neutrophil tissue load, function, and release of phlogistic reactive oxygen species and proteases. The systemic inflammatory response syndrome (SIRS), a massive pro-inflammatory immune state, is associated with delayed neutrophil apoptosis, however, the systemic circulating factors and intracellular signal transduction pathways important in regulating neutrophil apoptosis in SIRS are poorly described. Neutrophils isolated from patients with SIRS on admission to the intensive care unit showed significantly (p<.01) delayed spontaneous neutrophil apoptosis compared with healthy neutrophils as quantified using annexin V-FITC and terminal deoxyuridine triphosphate (dUTD) nick end labeling (TUNEL) flow cytometry methods. Plasma from SIRS patients markedly (41.5+/-7.2%, p<.01) inhibited apoptosis of healthy neutrophils compared with controls (69.7+/-4.8%) indicating the presence of soluble circulating factors that can modify the expression of neutrophil apoptosis. Various pro-inflammatory (IL-6, granulocyte macrophage colony-simulating factor, interleukin (IL)-1beta, tumor necrosis factor-alpha) mediators, known to modulate neutrophil apoptosis in vitro, were elevated in the plasma of our cohort of SIRS patients compared with controls. However, the anti-apoptotic effect of SIRS plasma was specifically attenuated (75.5%, p<.01) by neutralizing SIRS plasma of granulocyte macrophage-colony-stimulating factor, but not IL-6, IL-1beta, tumor necrosis factor-alpha. Although the anti-inflammatory cytokine IL-10 was elevated in SIRS plasma (median level 7.2 pg/mL), further boosting SIRS plasma with recombinant human IL-10 (10 ng/mL, levels found in septic shock patients) significantly countered (63.8%, p<.01) the inhibitory effect of SIRS plasma on neutrophil apoptosis. Suppression of neutrophil apoptosis was concomitant with delayed spontaneous elevation of reactive oxygen species, quantified as peroxide production, and reversed by addition of neutralizing antibodies to GM-CSF, and recombinant human IL-10 to SIRS plasma. These results identify circulating GM-CSF as a significant inhibitor of neutrophil apoptosis in patients with SIRS, and that this effect can be countered by boosting SIRS plasma with IL-10. GM-CSF and IL-10 appear to modulate neutrophil apoptosis by altering reactive oxygen species generation in neutrophils.

Adolescent↗
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

In-situ emergency paediatric surgery in the intensive care unit.

The role of surgery in the intensive care unit (ICU) remains unclear. Although previously shown not to increase morbidity for patent ductus arteriosus ligation, Broviac catheter insertion, and recently, general neonatal and paediatric surgery, there remains a reluctance to operate on sick patients in the ICU (in-situ surgery, ISS). A retrospective study of 25 critically ill children and neonates who underwent ISS was performed. Surgery was aided by operating loupes and a high-intensity headlight. ISS was not associated with any morbidity, and although a 36% mortality occurred in this small series, in no case was this due to ISS. ISS avoids the risks of transfer to the operating theatre and the potential delays in theatre access. Our results suggest that ISS in a tertiary-level paediatric surgical hospital is safe and does not impact adversely on clinical outcome.

Critical Illness↗
PubMed1997

External carotid artery ligation for life-threatening hemorrhage in exsanguinating orbital facial congenital hemangiopericytoma.

A 7-week-old infant with a locally invasive, orbital, congenital hemangiopericytoma underwent emergency external carotid artery (ECA) ligation for exsanguinating hemorrhage from an intraoral biopsy site. ECA ligation was successful in controlling the life-threatening hemorrhage and in reducing tumor size and vascularity. The location and extensive nature of the tumor prevented primary excision. Preoperative adjuvant chemotherapy was unsuccessful in controlling tumor growth. After ECA ligation, with reduction in tumor bulk and blood supply, the tumor was radically excised. This technique has important implications in the management of patients with extensive hemangiopericytomas or sino-facial tumors previously regarded as unresectable and which present with life-threatening hemorrhage.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Evolving management of common bile duct stones in the laparoscopic era.

The role of laparoscopic duct exploration in the management of common bile duct (CBD) stones is unclear. The aim of this study is to audit the current management of choledocholithiasis in our unit and to report on the introduction of laparoscopic management, comparing it with established techniques. Over a 5-year period, 173 patients presented with CBD stones. In 105 (61%) patients, primary management of choledocholithiasis was by endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES) which was successful in 85 (81%) cases. Of the 20 patients with retained stones following ES, 18 underwent subsequent surgical exploration. Fifty (29%) patients underwent open CBD exploration as a primary treatment, resulting in complete clearance in 43 (86%) cases. Retained CBD calculi following open surgery occurred in seven cases and were ultimately treated by post-operative ES (n = 5), and observation (n = 2). Eighteen (10%) patients underwent primary laparoscopic CBD exploration. Four cases were converted to open surgery. Of the 14 completed laparoscopic duct explorations, 12 (86%) were successful. Two patients had retained stones, requiring secondary treatment with ERCP and ES. There was no mortality in the entire series. The complication rate was 12.4% with ERCP, 14% with open surgery, and zero with laparoscopic CBD exploration. There was no significant difference in hospital stay between groups. We conclude that the management of choledocholithiasis is in evolution, and early results suggest that laparoscopic CBD exploration compares favourably with established open surgical and endoscopic methods.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMedDate not supplied

Helicobacter pylori does not play a role in the aetiology of acute appendicitis.

The aetiology of acute appendicitis remains uncertain. H. pylori is viable outside the gastroduodenum, however its pathological role outside this area has not been fully investigated. Ten consecutive patients with a histological diagnosis of acute appendicitis were investigated for H. pylori status by serology, and by culture, histology, and polymerase chain reaction (PCR) analysis of the appendiceal specimens. One patient had positive serology for H. pylori, however PCR analysis was negative. Culture failed to reveal H. pylori colonies. Histology in 5 cases did reveal organisms with a morphological appearance of H. pylori, but PCR analysis confirmed that H. pylori was not present. Using a variety of methods, with PCR acting as the 'gold standard', we have shown that H. pylori is not associated with acute appendicitis.

Acute Disease↗