Search PubMed⌕ Search

Biomedical subjects

B O'Connor

Publications and source records attributed to B O'Connor.

At least 55 records · Page 3Linked to original sources
PubMed1996

The influence of alfentanil pre-treatment on ventilatory effects of doxapram following induction of anaesthesia with propofol.

BACKGROUND: Hypoventilation may occur following induction of anaesthesia with propofol and is potentiated by concurrent use of opioid drugs. This effect is undesirable in patients who will continue to maintain spontaneous respiration during anaesthesia and surgery. The analeptic drug doxapram is known to have selective respiratory stimulatory effects but its action during induction of anaesthesia has been inconsistent. METHOD: In a double-blind, placebo-controlled study, the influence of alfentanil pre-treatment on the ventilatory effects of doxapram given during induction of anaesthesia with propofol was studied in 40 patients. Four groups of ten patients (two groups pre-treated with 7 micrograms.kg-1 of alfentanil and two groups with saline) were randomly allocated to receive either 0.5 mg.kg-1 doxapram or saline following infusion of propofol to loss of verbal contact. RESULTS: In the groups that received doxapram, minute volumes were significantly increased and end-tidal carbon dioxide concentrations were significantly reduced compared to control groups, although the duration and extent of these effects were less in the group that received alfentanil. Doxapram also reversed an alfentanil-induced reduction in respiratory rate. No adverse cardiovascular or neurological stimulatory effects of doxapram were evident at any time. CONCLUSION: We conclude that doxapram 0.5 mg.kg-1 is effective in augmenting ventilation that has been obtunded following induction of anaesthesia with propofol in patients pre-treated with alfentanil.

Adolescent↗
PubMed1996

Mapping reentry around atriotomy scars using double potentials.

Supraventricular arrhythmias, often seen in patients after cardiac surgery, may be associated with scars produced in the atria at the time of surgery. Double potentials, found in the presence of functional or anatomical block, can define the limits and critical regions of a reentrant circuit associated with the atriotomy scars. We describe six patients with seven distinct atrial tachycardias in whom atriotomy scars were successfully mapped during intraatrial reentry utilizing the presence and interelectrogram relationship of observed double potentials. The reentrant circuit was mapped in all patients by following the relationship between double potentials along the surgical scar, assuming that they would be widely split in the middle of the scar and merge into a single continuous fractionated potential at the apex of the scar. At this site, atrial pacing was performed to entrain the tachycardia and confirm the participation of the atriotomy scar in the clinically relevant atrial tachycardia. Radiofrequency ablation was performed from the site of electrogram fusion to the nearest anatomical obstacle. Five of seven atrial tachycardias were successfully ablated utilizing this technique over a mean follow-up of 10 months. We proposed that these double potentials and their interelectrogram relationship are an effective means of mapping atriotomy scars and guiding successful radiofrequency ablation.

Action Potentials↗
PubMed1996

Expression of RANTES mRNA and protein in airways of patients with mild asthma.

Chemoattractant cytokines (chemokines) such as RANTES, are potent chemoattractants for eosinophils, T lymphocytes, and monocyte/macrophages. We examined RANTES mRNA and protein expression in bronchial biopsies and bronchoalveolar lavage (BAL) cells from patients with mild asthma on beta 2-adrenergic agonist therapy only. Using quantitative polymerase chain reaction (PCR), mean RANTES starting cDNA was 110 +/- 18 fg/pg beta-actin in asthmatics compared with 33.7 +/- 11.0 fg/pg in normals (p < 0.003) but there was no significant difference in RANTES mRNA expression in BAL cells between the two groups. Immunohistochemical staining of cryostat sections of bronchial biopsies with an anti-RANTES antibody using peroxidase antiperoxidase method revealed constitutive staining in airway epithelial cells, airway smooth muscle, and subepithelial cells. However, there was no difference in the number of RANTES-staining cells between normal subjects and asthmatics despite significantly increased numbers of CD4+ T-cells, CD68+ macrophages, and MBP+ eosinophils in mucosal biopsies obtained from asthmatics. Double-staining revealed expression of RANTES in a proportion of CD3+ T lymphocytes. Thus, RANTES is constitutively expressed in the airways and RANTES mRNA is elevated in airways of patients with mild asthma, supporting a role for RANTES in normal and asthmatic airways.

Actins↗
PubMed1996

Hepatic and vena cava resection using cardiopulmonary bypass with hypothermic circulatory arrest.

When large hepatic or retroperitoneal tumors encroach upon hepatic veins or vena cava and make conventional resection hazardous, the most commonly used method of hepatic resection or vena cava reconstruction includes hepatic vascular exclusion, at times with venovenous bypass or aortic occlusion. These techniques result in warm liver ischemia, and may be accompanied by significant systemic hypotension, despite aggressive central venous preloading. Hepatic lobe (two patients) and retroperitoneal sarcoma (one patient) resections were done in a cold, bloodless field without significant complications. Standard cardiopulmonary bypass techniques with heparin and cardioplegia were used. Systemic circulatory arrest was done at 15 degrees C with isolated retrograde perfusion of the brain through the jugular veins. Hepatic vein and vena cava reconstructions were performed with arrest times of between 30 and 78 minutes. Blood loss was gradual and easily controlled, occurring during the rewarming phase when clot formation was inhibited by cold and heparin.

Adult↗
PubMed1995

Identification and localisation of a synaptosomal membrane prolyl endopeptidase from bovine brain.

Prolyl endopeptidase, which has long been recognised for its importance in the degradation of several neuropeptides such as thyroliberin, luteinising hormone releasing hormone, angiotensin, substance P and neurotensin, has been widely characterised as a cytosolic enzyme. However, in this paper, we report the presence of a prolyl endopeptidase activity in the particulate fractions of bovine brain, which is distinct from that in the cytoplasm. This previously uncharacterised activity was found to reside in the synaptosomal membranes, a location which is highly significant for the inactivation of neuropeptides in brain. Following vigorous salt washing and osmotic shock, the prolyl endopeptidase activity was released from the membranes by treatment with the detergent Triton X-100, and was partially purified by gel filtration on a Sephacryl S-200HR column. This prolyl endopeptidase activity was shown to have a molecular mass (87 kDa) higher than the cytosolic prolyl endopeptidase but, from initial investigation, appears to demonstrate a similarly broad substrate specificity towards proline-containing neuropeptides. The partially purified enzyme was inhibited by certain thiol-protease inhibitors and was also found to be sensitive to the metal chelator 1,10-phenanthroline.

Animals↗
PubMed1995

Tiotropium bromide (Ba 679 BR), a novel long-acting muscarinic antagonist for the treatment of obstructive airways disease.

Tiotropium bromide (Ba 679 BR) is a novel potent and long-lasting muscarinic antagonist that has been developed for the treatment of chronic obstructive airways disease (COPD). Binding studies with [3H]tiotropium bromide in human lung have confirmed that this is a potent muscarinic antagonist with equal affinity for M1-, M2- and M3-receptors and is approximately 10-fold more potent than ipratropium bromide. Tiotropium bromide dissociates very slowly from lung muscarinic receptors compared with ipratropium bromide. In vitro tiotropium bromide has a potent inhibitory effect against cholinergic nerve-induced contraction of guinea-pig and human airways, that has a slower onset than atropine or ipratropium bromide. After washout, however, tiotropium bromide dissociates extremely slowly compared with the dissociation of atropine and ipratropium bromide. Measurement of acetylcholine (ACh) release from guinea-pig trachea shows that tiotropium bromide, ipratropium bromide and atropine all increase ACh release on neural stimulation and that this effect is washed out equally quickly for the three antagonists. This confirms binding studies to transfected human muscarinic receptors which suggested that tiotropium bromide dissociates slowly from M3-receptors (on airway smooth muscle) but rapidly from M2 autoreceptors (on cholinergic nerve terminals). Clinical studies with inhaled tiotropium bromide confirm that it is a potent and long-lasting bronchodilator in COPD and asthma. Furthermore, it protects against cholinergic bronchoconstriction for > 24 h. This suggests that tiotropium bromide will be a useful bronchodilator, particularly in patients with COPD, and may be suitable for daily dosing. The selectivity for M3- over M2-receptors may also confer a clinical advantage.

Acetylcholine↗
PubMed1995

A study of a synaptosomal thyrotropin releasing hormone-inactivating pyroglutamate aminopeptidase from bovine brain.

Pyroglutamate aminopeptidase type II is a highly specific membrane-bound neuropeptidase that has the ability to remove N-terminal pyroglutamate (Glp) from Thyrotropin Releasing Hormone (Glp-His-Pro-NH2) or very closely related tripeptides or tripeptide amides. In this paper we report on the purification and characterisation of a pyroglutamate aminopeptidase activity from the synaptosomal membranes of bovine brain. The Triton X-100 solubilised enzyme was purified nearly 600-fold by a combination of conventional column chromatography steps with a recovery/yield of 17.0%. Phase-partitioning experiments with Triton X-114 showed the activity to be an integral membrane protein. This detergent-solubilised pyroglutamate aminopeptidase activity was found to have a relative molecular mass of 240 kDa on a calibrated S-200 column. HPLC analysis on a C18 reverse-phase column showed that the purified activity displayed a very narrow substrate specificity cleaving only Thyrotropin Releasing Hormone (TRH) or the very closely related acid-TRH, LHRH (1-3) and the TRH-analogue (methyl-His)-TRH and had a Km of 100 microM for the fluorimetric substrate Glp-His-Pro-methyl-coumarin. The enzyme was inactivated by the metalchelator 1,10-ortho-phenanthroline but showed less sensitivity to EDTA. It also showed some inhibition by thiol protease inhibitors such as iodoacetate and n-ethyl-maleimide. In summary, we have purified a pyroglutamate aminopeptidase from the synaptosomal membrane of bovine brain. This enzyme displays characteristics consistent with it being classified as a PAP type II neuropeptidase with only minor differences from other proteases in this group.

Amino Acid Sequence↗
PubMed1995

Evaluation of the efficacy and safety of amethocaine gel applied topically before venous cannulation in adults.

We have assessed in a placebo-controlled, double-blind trial, the efficacy and safety of an amethocaine gel preparation for alleviating the pain of venous cannulation. Forty-two unpremedicated adult patients were allocated randomly to receive either amethocaine gel 1 g (4% w/w) or placebo gel 1 g applied to the dorsum of the hand for 40 min before venous cannulation. After removal of the gel, a 20-gauge cannula was inserted and the pain of cannulation assessed by a three-point rank score and a 100-mm visual analogue scale: 90% of patients who received amethocaine reported clinically acceptable topical anaesthesia. Both verbal rating scores and visual analogue scores for pain were significantly less with amethocaine. Slight erythema associated with amethocaine occurred in one patient and slight itching in two patients. No other adverse features were evident.

Administration, Topical↗
PubMed1995

Lipids and lipoprotein(a) as risk factors for vascular disease in patients on renal replacement therapy.

A large cohort of patients on renal replacement therapy were screened for the presence of symptomatic arterial disease affecting the coronary, cerebral or peripheral circulations. Ninety-two of 325 patients were found to have vascular disease. Those with vascular disease had significantly higher median lipoprotein(a) [Lp(a)] levels than those without (38.4 vs 14.2 mg/dl, P < 0.001), with a preponderance of Lp(a) levels greater than 30 mg/dl (58% vs 25% P < 0.001). Apolipoprotein(a) [apo(a)] isoform distribution was similar between the groups, but those with vascular disease had higher Lp(a) levels in the S2, S3/S4 and S4 isoform types. Comparison of 76 matched pairs of patients confirmed elevated Lp(a) levels in those with vascular disease. These patients also had significantly higher total cholesterol (6.66 vs 6.02 mmol/l) and low-density lipoprotein cholesterol (4.49 vs 3.86 mmol/l). Only Lp(a) was independently associated with vascular disease (P = 0.02). Elevated Lp(a) levels are significantly associated with the presence of vascular disease in patients on renal replacement therapy and may constitute another risk factor for the development of such disease in these patients.

Adult↗
PubMed1995

The Victoria Declaration--a unifying force.

The Victoria Declaration, the policy document which resulted from the First International Heart Health Conference--'Bridging the Gap: Science and Policy in Action'--is an historic document. Advances in cardiovascular disease prevention, intervention and research as well as in heart health promotion have been frequent and significant. At the same time, a lack of appreciation of the need for a coordinated effort between clinicians, researchers, epidemiologists, community health professionals and others in the health field has meant that we have not been able to capitalize on the opportunity for greater success. The Victoria Declaration highlights the fact that a comprehensive approach to cardiovascular disease prevention needs to expand partnerships well beyond the health sector into many areas of policy development both within and outside government and in the private and voluntary sector, among others. The key message of the declaration is that our best effort will be a unified, systematic effort that marries the preventive, clinical and research approaches with those of policy makers, governments, private sector and others. It is imperative that health professionals recognize this. The declaration outlines a comprehensive framework for cardiovascular disease prevention, advocating a public health approach, targeted towards the population at large and focusing on the reduction of the major risk factors. It suggests a number of key strategies and advocates a research agenda. The declaration is a document that has international scope and recognizes that global partnerships are necessary to assist developing countries (that are now experiencing increasing rates of cardiovascular disease) in the fight against this disease.

Cardiovascular Diseases↗
PubMed1994

Diketopiperazine formation and N-terminal degradation in recombinant human growth hormone.

A new degradation process has been identified that occurs in recombinant DNA-derived human growth hormone. Non-enzymatic cyclization of the first two amino acids from the N-terminus and subsequent cleavage results in the formation of a diketopiperazine and a truncated variant of rhGH. The truncated protein was separated using hydrophobic interaction chromatography and identified as desPhe1Pro2-rhGH using N-terminal sequence analysis, tryptic mapping, and mass spectrometry.

Amino Acid Sequence↗
PubMed1994

Risk factors for cardiovascular disease in IDDM. A study of identical twins.

Patients with insulin-dependent diabetes mellitus (IDDM) have an excess mortality, predominantly attributable to cardiovascular disease. To determine the effect of IDDM on potential risk factors for cardiovascular mortality, we studied subjects from the British Diabetic Twin Study Group. Forty-five identical twin pairs discordant for IDDM were recruited in addition to 45 matched nondiabetic singleton control subjects. All were selected to be normotensive and to have normal albumin excretion rates. Four variables differed significantly between the diabetic twins and their nondiabetic identical co-twins: diabetic twins had higher systolic blood pressure (sBP) ([mean +/- SD] 127 +/- 17 vs. 123 +/- 18 mmHg, P < 0.05), high-density lipoprotein (HDL) cholesterol (1.36 +/- 0.31 vs. 1.25 +/- 0.29 mM, P < 0.05) and fibrinogen (3.23 +/- 0.81 vs. 2.98 +/- 0.71 mg/ml, P < 0.05) but lower factor VII (114 +/- 34 vs. 122 +/- 31%, P < 0.05). All four of these risk factors were significantly correlated (P < 0.001) within the identical twin pairs, as were the other risk factors. These significant correlations within twins for the risk factors studied reflects the impact of shared genetic and environmental influences. IDDM affects sBP, HDL cholesterol, fibrinogen, and factor VII, but only sBP and fibrinogen are affected adversely.

Adult↗
PubMed1993

Reversal of nitroglycerin tolerance in vitro by the cGMP-phosphodiesterase inhibitor zaprinast.

Following in vitro exposure of rat aortic rings to 550 microM nitroglycerin for 1 h, tolerance was demonstrated by a significant increase in EC50 values for nitroglycerin-induced relaxation. However, cross-tolerance to sodium nitroprusside was not observed. Co-incubation of aortic rings with the cGMP-phosphodiesterase (cGMP-PDE) inhibitor zaprinast (10 microM), during incubation with 550 microM nitroglycerin, did not prevent the development of tolerance. However, the addition of 0.30 or 10 microM zaprinast to tolerant aortic rings did restore responsiveness to nitroglycerin. The increase in cGMP in tolerant aortic rings in response to 300 nM nitroglycerin (2-4 fmol/micrograms) was significantly less than that observed for non-tolerant rings (6.6-12 fmol/micrograms), but cGMP levels were restored in tolerant rings by zaprinast (7-12 fmol/micrograms). These data suggest that inhibition of vascular cGMP-PDE activity does not prevent the development of tolerance in vitro, but does reverse the loss of vasorelaxant potency to nitroglycerin via restoration of intracellular cGMP levels.

3',5'-Cyclic-GMP Phosphodiesterases↗