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Biomedical subjects

C R Bailey

Publications and source records attributed to C R Bailey.

At least 19 recordsLinked to original sources

BCG (Bacille Calmette-Guérin) HspCs (heat-shock protein-peptide complexes) induce T-helper 1 responses and protect against live challenge in a murine aerosol challenge model of pulmonary tuberculosis.

The need for an effective TB (tuberculosis) vaccine remains acute, with tuberculosis still one of the major killers worldwide and 3 million new infections annually. We report here on the immune responses elicited by HspCs (heat-shock protein-peptide complexes) isolated from BCG (Bacille Calmette-Guérin) vaccine. These HspCs elicit both the appropriate cellular and protective immune responses required to merit their further development as TB vaccine candidates.

Aerosols↗

Management of outpatient ear, nose and throat surgery.

In the year under review there have been steady advances in anaesthesia. Premedication in children is best achieved with oral midazolam formulated in flavoured syrups, and the inhalational induction of anaesthesia may be accomplished using sevoflurane. Pain management of the most common surgical procedure performed in children, tonsillectomy/adenoidectomy, is still sub-optimal, but combinations of opioids and non-steroidal anti-inflammatory drugs are helpful. There are, however, some concerns regarding the possible increases in postoperative blood loss after tonsillectomy when non-steroidal anti-inflammatory drugs are used. Middle ear surgery leads to a high incidence of postoperative nausea and vomiting, and these are best managed by utilizing a total intravenous anaesthetic technique with propofol, the avoidance of nitrous oxide, and administration of dexamethasone and a 5-hydroxytryptamine receptor antagonist such as ondansetron.

Journal Article↗

Impact of heating-degree-day accumulation during bermudagrass hay storage on nutrient utilization by lambs.

Spontaneous heating in stored alfalfa (Medicago sativa) has reduced forage quality and DM and N digestibility through microbial respiration and Maillard polymer formation. The impact of heating-degree-day (HDD) accumulation in stored bermudagrass (Cynodon dactylon [L.] Pers.) was evaluated for its effect on nutrient utilization by lambs. Twenty Rambouillet wether lambs (53.1 +/- 0.74 kg) were used in a completely randomized total collection experiment. The hays selected for this study had previously undergone spontaneous heating, producing either 5, 119, 201, 273, or 401 HDD (> 35 degrees C) during a 60-d storage period. Lambs were offered diets of these hays at 1.5% of BW. Dry matter intake did not differ (P = 0.59) among hays. Linear relationships were detected between HDD and apparent digestibilities of DM (y = 59.1 - 0.016x; P < 0.01; R2 = 0.37), OM (y = 59.3 - 0.017x; P < 0.01; R2 = 0.43), NDF (y = 66.4 - 0.012x; P = 0.01; R2 = 0.30), and hemicellulose (y = 74.0 - 0.012x; P = 0.02; R2 = 0.27). Similarly, significant regressions were observed for fecal N excretion (g/d; y = 4.70 + 0.004x; P < 0.01; R2 = 0.68), apparent N absorbed (g/d; y = 7.4 - 0.005x; P < 0.01; R2 = 0.50), apparent N absorption (%; y = 61.2 - 0.038x; P < 0.01; R2 = 0.71), apparent neutral detergent insoluble nitrogen digestibility (%; y = 85.8 - 0.026x; P = 0.01; R2 = 0.73), and apparent acid detergent insoluble nitrogen digestibility (%; y = 1.5 + 0.101x; P < 0.01; R2 = 0.62). Therefore, spontaneous heating during the storage of bermudagrass hay has a negative effect on dry matter and fiber digestion and nitrogen absorption by lambs.

Animal Feed↗

Evaluation of B and T-cell responses in chimpanzees immunized with Hepagene, a hepatitis B vaccine containing pre-S1, pre-S2 gene products.

Approximately 5-10% of healthy young adults receiving the commercially available hepatitis B vaccine (either serum derived or recombinant) fail to mount an adequate immune response. This nonresponder rate has prompted the demand for more immunogenic vaccines. An alternative to the currently licensed hepatitis B vaccines is Hepagene, a novel recombinant hepatitis B vaccine containing S, pre-S1 and pre-S2 antigenic components, produced in the mouse C127I clonal cell line after transfection of the cells with genes encoding the three antigens. In this study, chimpanzees were immunized with Hepagene to study the humoral and cellular immune responses to this vaccine. Two out of the three animals immunized with this vaccine seroconverted 4 weeks after their first injection and all of the animals elicited high anti-HBs levels that were maintained for at least 28-30 weeks after their third immunization. The anti-HBs levels elicited in these animals protected them against an experimental challenge with HBV. Peripheral blood mononuclear cells (PBMCs) obtained from immunized animals could be stimulated in vitro by rHBsAg and peptides representing regions within all three of the viral envelope proteins. Additionally, an anti-id that mimics the a determinant in the S-region of HBsAg could also stimulate in vitro proliferation of PBMCs from these immune animals. These results indicate that this new recombinant HBV vaccine encoding all three of the surface antigen proteins is highly immunogenic is that it can stimulate strong cellular and humoral immune responses.

Animals↗

The role of continuous positive airway pressure during weaning from mechanical ventilation in cardiac surgical patients.

We investigated the effects of providing patients with continuous positive airway pressure during a short weaning period from mechanical ventilation to extubation. Following elective primary aortocoronary bypass surgery employing cardiopulmonary bypass, 80 patients received intermittent positive pressure ventilation for 5 h. At the end of this time patients were randomly allocated to one of the following three groups for a 2 h period of spontaneous respiration prior to extubation: group CPAP0 = T-piece circuit (n = 27); group CPAP5 = 5 cmH2O of continuous positive airway pressure (n = 27); group CPAP10 = 10 cmH2O of continuous positive airway pressure (n = 26). Following extubation, pulmonary gas exchange was assessed after 1, 2, 4, and 24 h. All patients had good pre-operative lung function. There was a significant increase in the median alveolar-arterial oxygen partial pressure difference and a decrease in the oxygenation index in all three groups during the period of added inspired oxygen which persisted until 24 h post-extubation, but there were no differences between the groups. In patients with good pre-operative lung function requiring primary aortocoronary bypass surgery, the use of continuous positive airway pressure confers no advantage over a simple T-piece attachment during the short period of weaning from mechanical ventilation to extubation.

Aged↗

Randomized placebo-controlled double-blind study of three aprotinin regimens in primary cardiac surgery.

The serine proteinase inhibitor aprotinin significantly reduces postoperative blood loss in patients requiring cardiac surgery using cardiopulmonary bypass. This study compared two low-dose regimens with administration of high-dose aprotinin and a control protocol to determine whether the dose of aprotinin could be greatly decreased but still maintain efficacy after primary cardiac surgery. Some 100 patients were randomly assigned to one of four groups: control group (0.9 per cent saline placebo, n = 25); high-dose group (aprotinin 2 x 10(6) kallikrein inactivator (KI) units intravenous patient bolus and 0.5 x 10(6) KI units h-1 plus 2 x 10(6) KI units into pump prime, n = 25); prime group (aprotinin 2 x 10(6) KI units added to the pump prime, n = 24); and patient group (aprotinin 10(6) KI units intravenous patient bolus plus 10(6) KI units added to the pump prime, n = 26). Only patients from the high-dose and patient groups had reduced intraoperative blood loss, but patients from all three aprotinin-treated groups demonstrated a significant decrease in median postoperative blood loss compared with the control group (high-dose 350 ml, prime 420 ml, patient 340 ml versus control 780 ml; P < 0.001). There was an even greater reduction in measured median postoperative haemoglobin loss within the chest drains in the treated compared with the control patients (high-dose 15 g, prime 24 g, patient 14 g versus control 47 g; P < 0.001). These decreases were statistically the same for all the treated groups; it is possible to lower the dose of aprotinin to approximately one-third of the currently recommended dosage and still obtain significantly reduced postoperative blood loss in primary cardiac surgery.

Aprotinin↗

Diamorphine-bupivacaine mixture compared with plain bupivacaine for analgesia.

We have studied the efficacy of two extradural infusions (10 ml h-1) in 50 patients in active labour. Patients in the diamorphine group (n = 25) received 0.0625% plain bupivacaine 6.25 mg h-1 mixed with 0.005% diamorphine 0.5 mg h-1 and those in the control group (n = 25) received 0.125% plain bupivacaine 12.5 mg h-1. Both groups received intermittent "top-ups" of 0.25% bupivacaine 10 ml when indicated. Although median pain scores during the infusion were similar in both groups, patients in the diamorphine group indicated greater satisfaction with the infusion (88% very satisfied, compared with 52% in the control group (P < 0.02)). There were no differences in the incidence of hypotension, instrumental vaginal delivery, number of "top-ups", duration of the second stage or extent of motor block. However, patients in the diamorphine group had a high incidence of pruritus (44%, compared with 0% in the control group (P < 0.01)).

Adolescent↗

A simple method for the maintenance of oxygen saturation following intravenous induction of anaesthesia with propofol.

One hundred unpremedicated fit adult patients having elective minor day-stay surgery and general anaesthesia were randomly allocated to one of two groups. During 30 s of intravenous propofol administration (2.5 mg.kg-1), study group patients (n = 50) were instructed to take three vital capacity breaths of room air, whilst control group patients (n = 50) were given no specific instructions. Pulse oximetry was continuously recorded over the next 5 min and the lowest oxygen saturation was noted. Pre-induction oxygen saturation was the same for both groups, but the lowest median oxygen saturation in the study group patients was 94% versus 88% in the control group patients (p < 0.001). Oxygen saturation returned to the pre-induction value significantly earlier in the study group patients compared with controls (97 s vs 135 s, p < 0.01). These results demonstrate that significant desaturation occurs in patients following intravenous induction of anaesthesia with propofol. This desaturation may be attenuated by asking patients to take three vital capacity breaths of room air during induction of anaesthesia.

Adult↗

Randomised placebo controlled double blind study of two low dose aprotinin regimens in cardiac surgery.

OBJECTIVE: To determine whether two low dose aprotinin regimens produce clinically significant reductions in postoperative blood loss compared with a control group. DESIGN: A randomised double blind placebo controlled study. SETTING: A regional cardiothoracic unit in London. PATIENTS: 79 patients were consecutively allocated to one of three groups. All patients had primary elective surgery with standard anaesthetic and surgical techniques, and no patients were withdrawn from the study. INTERVENTIONS: Group K patients (n = 27) received aprotinin (10(6) kallikrein inactivator units (KIU) into the pump prime whereas group L patients (n = 27) received an intravenous bolus of aprotinin (0.5 x 10(6) KIU) after induction of anaesthesia and 10(6) KIU was added to the pump prime. A third group (group J, n = 25) received 0.9% saline placebo. MAIN OUTCOME MEASURES: After insertion of the chest drains at the end of cardiopulmonary bypass, blood losses were measured hourly until the drains were removed 18 to 24 h later. Total haemoglobin loss into the chest drains was calculated. RESULTS: Both aprotinin treated groups showed significantly less postoperative blood loss than controls (medians: group K, 400 ml; group L, 400 ml; v controls 780 ml; p < 0.001) and there was even less measured postoperative haemoglobin loss within the chest drains in both the aprotinin treated groups than in the controls (medians: group K, 16 g; group L, 19 g; v controls, 47 g; p < 0.001). CONCLUSION: In primary cardiac surgery the dose of aprotinin may be reduced by about 80% from the recommended high dose schedule and still significantly reduce postoperative blood loss compared with placebo.

Aprotinin↗

Reheparinisation requirements after cardiopulmonary bypass in patients treated with aprotinin.

OBJECTIVE: To determine reheparinisation requirements following protamine neutralisation after the discontinuation of cardiopulmonary bypass in a group of patients receiving "low dose" aprotinin compared with a control group. DESIGN: Randomised, placebo controlled study. SETTING: Regional cardiothoracic unit within a district general hospital. PATIENTS: 20 patients were consecutively allocated to one of two groups. All patients had a primary elective aortocoronary bypass operation using standard anaesthetic techniques and no patient was withdrawn from the study. INTERVENTIONS: Aprotinin group patients (n = 9) received aprotinin (1 x 10(6) kallikrein inactivator units (KIU)) as an intravenous bolus after the induction of anaesthesia, and 1 x 10(6) KIU was added to the pump prime. Control group patients (n = 11) received 0.9% saline placebo. MAIN OUTCOME MEASURES: Activated clotting time (ACT), heparin concentration, and heparin dose response (HDR) measured before, during, and after bypass. The HDR is an accurate method to determine the patients' in vitro response to heparin and is used to predict the dose of heparin required to attain an ACT of 400 seconds. RESULTS: Activated clotting times were similar in the two groups for the duration of the study. Heparin concentrations were zero in all patients before heparin administration and after protamine neutralisation. During bypass there was no difference between the groups. The median heparin dose response was the same in the two groups before the administration of heparin, but after the neutralisation of heparin with protamine after the discontinuation of bypass the HDR was significantly higher in the aprotinin group for up to one hour (median of 2.9 IU/ml v 1.25 in the control group at 10 minutes after protamine neutralisation, P < 0.01; 2.5 v 1.45 at 30 minutes, P < 0.05; and 2.9 v 1.6 at one hour, P < 0.001). CONCLUSION: Heparin requirements were nearly doubled in patients treated with aprotinin, who required reheparinisation for up to one hour after protamine. This relative "heparin resistance" cannot be explained by the presence of excessive protamine. Aprotinin may be a substrate for the N-carboxypeptidase that destroys protamine, thus indirectly enhancing and prolonging the activity of protamine.

Aprotinin↗

Anaesthesia: cheap at twice the price? Staff awareness, cost comparisons and recommendations for economic savings.

We questioned 50 anaesthetic staff about the costs of consumables used in routine anaesthetic practice. By means of a questionnaire staff were asked for estimates of the cost of 28 drugs, fluids and disposables. The responses were more accurate than in previous surveys; 47% of all the estimated costs were within 50% of the actual costs and 75% were within 100%. The costs of relatively expensive items such as blood, laryngeal mask airways, enflurane and isoflurane were consistently underestimated whereas cheaper items such as disposable syringes and electrocardiograph electrodes were consistently overestimated. Using 'state of the art' consumables, an hour-long anaesthetic in 1992 cost 14.02 pounds compared with 1.24 pounds in 1959. However, allowing for inflation, the cost today is actually equivalent to the cost in 1959. Since 1980 there has been no consistent pattern in drug prices, with some prices remaining the same, others falling and some increasing; all are, however, cheaper in real terms. It is possible to make substantial savings by using the more expensive drugs judiciously and by encouraging the use of low-flow, closed-circuit anaesthetic systems.

Anesthesia↗

Expression of a bacterial aspartase gene in Aspergillus nidulans: an efficient system for selecting multicopy transformants.

The Escherichia coli aspartase gene aspA has been expressed in the fungus Aspergillus nidulans using the powerful constitutive gpdA promoter and trpC terminator, both from A. nidulans. Multiple, but not single, copies of aspA overcome nutritional deficiencies resulting from the loss of catabolic NAD-linked glutamate dehydrogenase. They also circumvent certain nutritional deficiencies resulting from loss of the positive-acting regulatory gene product mediating nitrogen metabolite repression. Both of these cases of physiological suppression involve the aspartase-catalyzed catabolism of aspartate to ammonium plus fumarate. No physiological evidence for the opposite reaction leading to aspartate synthesis was obtained as multiple copies of aspA did not affect the phenotype resulting from the loss of anabolic NADP-linked glutamate dehydrogenase. The use of vectors containing aspA and recipients lacking NAD-linked glutamate dehydrogenase is an efficient means of selecting multicopy transformants in A. nidulans and also offers the possibility to select strains having increased aspartase levels from original transformants.

Aspartate Ammonia-Lyase↗

Inhibition of restriction in Streptomyces clavuligerus by heat treatment.

Inefficient transformation of Streptomyces clavuligerus protoplasts by DNA from the plasmid pIJ702, isolated from S. lividans, was attributed to restriction in view of the observation that efficient transformation was observed using modified pIJ702 (isolated from S. clavuligerus). The restriction system could be partially inhibited by treating protoplasts at 45 degrees C prior to transformation. This treatment increased the transformation frequencies of pIJ702 DNA by 100-fold and was used to introduce other plasmids into S. clavuligerus.

DNA Restriction Enzymes↗

Properties of in vitro recombinant derivatives of pJV1, a multi-copy plasmid from Streptomyces phaeochromogenes.

The 10.8 kb plasmid pJV1, isolated from Streptomyces phaeochromogenes, has a high copy number (about 150) and a broad host range among Streptomyces spp. Several pJV1 derivatives carrying the thiostrepton resistance gene (tsr) of S. azureus were made. One derivative, pWOR191, was shown to promote its own transfer and to mobilize chromosomal markers in S. lividans. Another derivative, pWOR109, was non-transmissible. Deletion in vitro of a segment of pWOR109 gave pWOR120 (5.6 kb), which has single BamHI and Bg/II sites shown to be capable of accepting 'foreign' DNA such as a previously cloned S. antibioticus DNA fragment encoding tyrosinase, giving vectors (pWOR125, pWOR126) with properties resembling the well-established multicopy vector pIJ702. Shuttle vectors capable of functioning in both S. lividans and Escherichia coli were also constructed. The region of pJV1 essential for replication and maintenance was localized to a 2.5 kb segment. Stable maintenance of pWOR109 and pWOR120 was observed in the presence of derivatives of pIJ101, the progenitor of pIJ702.

Chromosomes, Bacterial↗