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M Buckland

Publications and source records attributed to M Buckland.

8 recordsLinked to original sources
PubMed2006

Aspirin-treated human DCs up-regulate ILT-3 and induce hyporesponsiveness and regulatory activity in responder T cells.

Mature dendritic cells (mDCs) are potent antigen presenting cells, but immature DCs (iDCs) have been shown to have reduced antigen stimulatory capacity. Different strategies have been investigated to augment the tolerogenic capacity of dendritic cells (DCs). We demonstrate that in aspirin-treated human DCs, there is reduced expression of CD1a, HLA-DR and CD86, up-regulation of ILT-3 expression and marginal increases in PDL-1. Aspirin-treated DCs are partially resistant to phenotypic changes following maturational stimuli, such as lipopolysaccharide (LPS) or TNFalpha, IL-1alpha and PGE2. Aspirin-treated DCs demonstrate normal endocytic function, but have a reduced ability to stimulate allogeneic T cells, which is comparable to iDCs. Furthermore, they induce hyporesponsiveness and regulatory activity in responder naïve and memory T cells; for naïve T cells this is achieved more quickly and efficiently than with iDCs. We investigated the mechanism of this regulatory activity and found that both cell-cell contact and inhibitory cytokine activity are involved, although no one cytokine predominates in importance. Blocking ILT-3 or IL-12 does not diminish the capacity of these DCs to induce regulation or Foxp3 expression on the regulatory T cells. Results demonstrate that aspirin-treated DCs display tolerogenic potential, which is of interest in their therapeutic potential in reducing chronic allograft rejection.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

A comparison of epidural ropivacaine infusion alone and in combination with 1, 2, and 4 microg/mL fentanyl for seventy-two hours of postoperative analgesia after major abdominal surgery.

UNLABELLED: Our aim in this prospective, randomized, double-blinded study was to compare the analgesic effectiveness and side effects of epidural infusions with ropivacaine 2 mg/mL alone (Group R; n = 60) and in combination with fentanyl 1 microg/mL (R1F; n = 59), 2 microg/mL (R2F; n = 62), and 4 microg/mL (R4F; n = 63) for up to 72 h after major abdominal surgery. Effective epidural neural blockade was established before surgery; postoperatively, the infusion rate was titrated to a maximum of 14 mL/h for analgesia. No additional analgesics other than acetaminophen were permitted during the infusion. The median of individual visual analog scale score with coughing were <20 mm for all groups (0 = no pain, 100 = worst pain) and was significantly lower (P < 0.01) for Group R4F at rest and with coughing (compared with Group R). Infusions were discontinued due to inability to control pain in significantly fewer patients in Group R4F (16%) than the other groups (34% to 39%; P < 0.01). For all groups, >90% of patients had no detectable motor block after 24 h. Hypotension, nausea, and pruritus were more common with the larger dose of fentanyl. We conclude that, after major abdominal surgery, an epidural infusion of ropivacaine 2 mg/mL with fentanyl 4 microg/mL provided significantly more effective pain relief over a 3-day period than ropivacaine alone or ropivacaine with lower concentrations of fentanyl. IMPLICATIONS: Postoperative epidural analgesic infusions are widely used, but there is little information regarding optimal strengths of opioid with local anesthetic. In this blinded, prospective study, we compared four different epidural infusion solutions for efficacy and side effects over a clinically useful postoperative period and conclude that an epidural infusion of ropivacaine 2 mg/mL with fentanyl 4 microg/mL was most effective.

Abdomen↗
PubMed1998

Domain-specific gene disruption reveals critical regulation of neuregulin signaling by its cytoplasmic tail.

Neuregulins are a multi-isoform family of growth factors that activate members of the erbB family of receptor tyrosine kinases. The membrane-anchored isoforms contain the receptor-activating ligand in their extracellular domain, a single membrane-spanning region, and a long cytoplasmic tail. To evaluate the potential biological role of the intracellular domain of the membrane-anchored neuregulin isoforms, we used a domain-specific gene disruption approach to produce a mouse line in which only the region of the neuregulin gene encoding almost the entire intracellular domain was disrupted. Consistent with previous reports in which all neuregulin isoforms were disrupted, the resulting homozygous neuregulin mutants died at E10.5 of circulatory failure and displayed defects in neural and cardiac development. To further understand these in vivo observations, we evaluated a similarly truncated neuregulin construct after transient expression in COS-7 cells. This cytoplasmic tail-deleted mutant, unlike wild-type neuregulin isoforms, was resistant to proteolytic release of its extracellular-domain ligand, a process required for erbB receptor activation. Thus, proteolytic processing of the membrane-bound neuregulin isoforms involved in cranial ganglia and heart embryogenesis is likely developmentally regulated and is critically controlled by their intracellular domain. This observation indicates that erbB receptor activation by membrane-bound neuregulins most likely involves a unique temporally and spatially regulated "inside-out" signaling process that is critical for processing and release of the extracellular-domain ligand.

Animals↗
PubMed1996

The association among gastric mucosal pH, endotoxemia, and low systemic vascular resistance after cardiopulmonary bypass.

OBJECTIVE: Previously, it was found that a number of patients suffer a "low systemic vascular resistance syndrome" after cardiopulmonary bypass, and this was hypothesized to be secondary to endotoxemia, resulting from intestinal ischemia during bypass. DESIGN: Prospective cohort. SETTING: University teaching hospital. PARTICIPANTS: Thirty-two patients undergoing cardiac surgery. INTERVENTIONS: A number of variables relating to adequacy of tissue perfusion were measured at seven time periods perioperatively: cardiac output, systemic vascular resistance, oxygen delivery and consumption, oxygen extraction ratio, gastric mucosal pH, serum lactate, and endotoxin levels. MEASUREMENTS AND MAIN RESULTS: Investigators could not find any association between systemic vascular resistance and mucosal pH or endotoxin levels after bypass. There were significant changes in oxygen flux and extraction ratio (p < 0.001) as well as serum lactate (p < 0.001). There was no significant change in endotoxin levels or mucosal pH. The systemic vascular resistance at 6 hours postbypass could be predicted from the vascular resistance reading at 1 hour postbypass by a regression equation. A significant correlation between systemic vascular resistance and mixed venous oxygen was found at 4 and 6 hours postbypass (p < 0.01) as well as with oxygen extraction (p < 0.01). There was a negative correlation between mucosal pH and serum lactate, particularly at 6 hours postbypass (p < 0.01). There was no correlation between mucosal pH and endotoxin levels, oxygen flux, or cardiac output. CONCLUSIONS: The investigators therefore could not find any evidence that intestinal ischemia during bypass, as measured by gastric mucosal pH, predisposes to endotoxemia, or low systemic vascular resistance after cardiac surgery.

Adult↗
PubMed1996

Continuous extradural infusion of ropivacaine for prevention of postoperative pain after major orthopaedic surgery.

We studied 151 patients undergoing total hip or knee arthroplasty, or cruciate ligament reconstruction in a multicentre study in Australia and New Zealand. Patients were openly allocated randomly to one of five treatment groups or to a control group. General anaesthesia was induced after introduction of extradural block with 0.5% ropivacaine. After surgery, patients received an extradural infusion of 0.2% ropivacaine at 6, 8, 10, 12 or 14 ml h-1 or received no postoperative extradural infusion (control group). All patients had access to i.v. PCA morphine for supplementary analgesia. Morphine consumption was lower in all treatment groups compared with the control group, decreasing with increasing ropivacaine infusion rate. Median VAS scores were lower in all ropivacaine infusion groups compared with the control group for the first 10 h of the study; however by the end of the study, VAS scores were similar in all groups. The higher ropivacaine infusion rates caused a slower convergence of spread of the initial sensory block and a higher degree of motor block. The overall incidence of side effects was similar, with the exception of a higher incidence of urinary retention and hypotension in the groups receiving the higher rates of ropivacaine. The quality of treatment scores were similar for all treatment groups (Br. J. Anaesth. 1996; 76: 606-610).

Adult↗
PubMed1994

Techniques and results in bilateral sequential single lung transplantation. The National Heart & Lung Replacement Service.

Lung transplantation continues to evolve as a therapeutic option for patients with end-stage lung disease. Bilateral sequential single lung transplantation (BSSLTx) is a recent addition to the lung transplant surgeon's armamentarium that incorporates the benefits of single lung transplantation in patients who require double lung replacement while avoiding the morbidity inherent in the en bloc double lung transplant procedure. Between November 1992 and October 1993, 17 recipients underwent 18 bilateral BSSLTx procedures for a variety of indications. In 53% of patients, the procedure was completed without the requirement for cardiopulmonary bypass. Telescoping of the bronchial anastomosis has proved satisfactory. Induction cytolytic therapy has not been utilized. Patients received methyl prednisolone from day 1 and as maintenance prednisolone therapy. Actuarial 1-year survival is 87%; 12 of the 15 survivors are in Functional Class I. BSSLTx is an evolving transplant option for patients who require double lung replacement. Definitive clinical diffusion of the procedure will depend upon intermediate and long-term outcomes for specific recipient pathologies.

Adult↗
PubMedDate not supplied

Value of postoperative assessment of cardiac allograft function by transesophageal echocardiography.

Heart transplantation now provides an acceptable therapy for patients with severe end-stage heart disease. Although patient outcome has significantly improved both early and late after heart transplantation, early morbidity and mortality continues to affect overall survival and may be unpredictable. In an attempt to identify factors that may assist in predicting early outcome after orthotopic heart transplantation, we assessed allograft function in 16 patients in the immediate postoperative period, 30 minutes after weaning from cardiopulmonary bypass by measuring the fractional shortening of the left ventricle with transesophageal echocardiography. In addition, standard hemodynamic indexes of allograft function (arterial blood pressure, pulmonary capillary wedge pressure, mean pulmonary artery pressure, and cardiac output) were obtained at this early time point. Early outcome was assessed by the duration and peak dose of inotrope support required after transplantation, requirement for mechanical support, and the duration of stay in the intensive care unit. Left ventricular fractional shortening 30 minutes after cardiopulmonary bypass was significantly lower in those patients requiring inotropic support (28.4% +/- 4.6% versus 43.7% +/- 3.5%, p < 0.05), whereas hemodynamic variables failed to distinguish these groups. In those patients requiring inotropes, there was a significant negative correlation of fractional shortening with the peak dose (r = -0.87, p < 0.01) and the duration of inotropic support (r = -0.62, p < 0.05). The total ischemic time of the allograft (206 +/- 22 minutes, range 77 to 359) did not correlate with the subsequent fractional shortening, but patients requiring inotrope support after the operation had significantly longer ischemic times (259 +/- 22 versus 138 +/- 22 minutes, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗