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Biomedical subjects

L Bromley

Publications and source records attributed to L Bromley.

At least 19 recordsLinked to original sources
PubMed2006

Pre-emptive analgesia and protective premedication. What is the difference?

The management of postoperative pain has been greatly informed by an increasing understanding of the basic science of pain transmission. The idea that analgesia given before the injury would be more effective than the same analgesia given after the injury was named pre-emptive analgesia. The evidence for this phenomenon in postoperative pain management has been very mixed. The methodological problems of such studies, and the difficulties of all the major outcome measures make comparison of the studies available difficult. In the 20 years since the concept was proposed there has been a change in anaesthetic practice that in effect incorporates pre-emptive analgesia with opiates. Evidence for any pre-emptive analgesic with non-steroidal anti-inflammatory drugs is very poor, but the use of local anaesthetic blocks continues to be an area of study. Pre-emptive use of analgesic drugs is not the magic bullet to prevent postoperative pain, but is a strategy of use, among others for managing postoperative pain. Protective analgesia is a strategy that has grown out of the same desire to give drugs before injury to reduce the pain experienced afterwards. In this case the drugs under study have not been primary analgesics, but adjuvant drugs used commonly in the non-acute pain arena. In particular, the drug gabapentin, and to a lesser extent its related drug pregabalin. These drugs have been given by mouth as a pre-medicant, 1 hour before surgery in a variety of operations. A recent meta-analysis of the existing literature shows reduction of postoperative morphine consumption but little reduction in reporting of opiate side effects. Pregabalin, which has a better pharmacokinetic profile, may be a better alternative, and is currently under study. Neither gabapentin nor pregabalin are licensed for use in postoperative pain, and it is unlike that the manufacturers will seek such a licence.

Acetaminophen↗
PubMed1999

Placental transfer of fentanyl in early human pregnancy and its detection in fetal brain.

We have investigated the transfer of fentanyl across the early human placenta in 38 women (8-14 weeks' gestation) undergoing termination of pregnancy. After administration of a bolus dose of fentanyl 2 micrograms kg-1 at induction of anaesthesia, maternal blood n = 38), placenta (n = 38), amniotic fluid (n = 38) and fetal brain (n = 7) samples were collected and assayed for fentanyl by radioimmunoassay. Fentanyl was detected in all placental and fetal brain samples but not in amniotic fluid. There was a rapid decrease in fentanyl concentrations in maternal serum after the bolus but placental concentrations had not started to decline 30 min later. There was no difference in placental drug concentrations at different gestational ages. These data suggest that there is rapid transfer of fentanyl to the fetus in early pregnancy and that the drug remains in fetal tissue for some time after the initial dose is given to the mother.

Abortion, Therapeutic↗
PubMed1998

Placental transfer of fentanyl in early human pregnancy.

To investigate the transfer of fentanyl across the early human placenta, we have collected samples of maternal blood and fetal fluids and/or blood, simultaneously, between 5 and 22 min following an intravenous bolus of fentanyl (1.5 microg/kg) to the mother. The pregnancies were between 6 and 16 weeks of gestation and scheduled for elective termination of pregnancy under general anaesthesia. Total fentanyl concentration was determined by radioimmunoassay in 11 pairs of first trimester maternal serum and fetal coelomic fluid samples, 14 pairs of maternal serum and amniotic fluid samples, seven series of first trimester maternal serum and coelomic and amniotic fluid samples, and 10 series of early second trimester maternal and fetal sera and amniotic fluid samples. Fentanyl was not detected in coelomic fluid samples at any gestational age and in amniotic fluid samples collected after 12 weeks of gestation. Measurable concentrations of fentanyl were found in maternal serum collected within 15 min after the initial bolus and in fetal serum collected between 10 and 12 min later. These findings indicate that fentanyl is transferred across the early placenta into the amniotic cavity and fetal blood circulation but not into the exocoelomic cavity. The distribution of this molecule inside the early gestational sac is probably influenced by the increased binding by maternal and fetal sera, its short half-life of distribution and the specific biology of the fetal fluid formation and composition.

Amniotic Fluid↗
PubMed1995

Loss of heterozygosity on chromosome 11 q in breast cancer.

AIMS: Chromosome 11q23 seems to be a site of frequent mutation in cancer. It also contains loci such as ataxia telangiectasia with possible importance in the pathogenesis of breast tumours. The short arm of chromosome 11 has been studied extensively in breast cancer, but the long arm, in particular the distal part, has been studied less frequently. Cytogenetic analysis has shown possible involvement of chromosome 11q in breast tumours. Chromosome transfer experiments have also implicated chromosome 11q in breast cancer. A high frequency of mutations might therefore be expected to occur on chromosome 11q in breast cancers. METHODS: Using restriction fragment analysis, the primary tumours of 41 patients with breast cancer were screened for mutations at five loci on chromosome 11q (D11Z1, INT2, (FGF3), DRD2, NCAM, and D11S29). RESULTS: Allelic loss occurred at a high frequency (59%) at D11S29. At NCAM, novel alleles were frequently seen on autoradiographs. Relatively low frequencies of mutation were detected at the other loci. Allelic loss at D11S29 was associated with the presence of lymph node metastases, but this may be a chance association. CONCLUSIONS: The frequency of allelic loss at the DS11S29 locus is high. The significance of novel alleles at NCAM and their relation to allelic loss at D11S29 are unclear. The results presented here do not permit fine mapping of a region of allelic loss, but suggest that the region of greatest loss lies distal to DRD2. The results provide further evidence for the importance of gene(s) near 11q23 in the pathogenesis of breast cancer, and of tumours in general.

Breast Neoplasms↗
PubMed1994

Non-isotopic in situ detection of mRNA for interleukin-4 in archival human tissue.

Non-isotopic in situ hybridisation (NISH) is a rapid and sensitive method currently used in molecular pathology to identify DNA in fresh and archival human biopsies. In this study we have extended NISH technology for mRNA detection to include the use of digoxigenin-labelled riboprobes to localise low abundance mRNA for interleukin-4 in paraffin embedded material (from active inflammatory bowel disease). As this methodological approach makes the retrospective study of cytokine gene expression in archival material possible for the first time, it could act as a prototype for studies of cytokine involvement in various human diseases.

Colitis, Ulcerative↗
PubMed1993

Quantification of oncogene dosage in tumours by simultaneous dual-label hybridization.

Gene amplification and allele loss occur in a variety of human tumours and some have prognostic value. Therefore, techniques which facilitate detection and quantification of gene dosage could have wide applicability in cancer research. Using the INT-2 gene as a model system, a quantitative procedure has been developed for measuring gene copy number using dual-label hybridization to DNA dot blots. A probe specific for the INT-2 gene was labelled with [alpha-32P]dCTP and a probe to beta-actin, the control locus, was labelled with [alpha-35S]dATP. Flat-bed scintillation counting was used to detect and separate the emissions resulting from each bound probe, and gene dosage was calculated from the ratio of INT-2 to the beta-actin probe compared with the ratio derived from constitutional DNA. Calculated ratios of greater than 1.22 and less than 0.78 indicated gene amplification and allelic loss respectively, at the 99% confidence limit derived from the population of 35 constitutional DNAs. The results were validated by RFLP analysis. It is expected that this technique will permit precise gene dosage quantification in many areas.

Alleles↗
PubMed1991

The collagen changes of Dupuytren's contracture.

In Dupuytren's contracture there is an increase in the ratio of type III to type I collagen. The objective of this study was to determine if fibroblasts from patients with Dupuytren's contracture have an intrinsic aberration in collagen production or whether local factors govern the collagen changes in Dupuytren's contracture. Using a new collagen micro-method, we found that fibroblasts cultured from palmar fascia affected by Dupuytren's contracture produced similar collagen to fibroblasts derived from the palmar fascia of age- and sex-matched patients with carpal tunnel syndrome. Furthermore, the collagen changes of Dupuytren's contracture could be reproduced in all cell lines by increasing fibroblast density. At high fibroblast density, type I collagen production was inhibited: a finding that could account for the increased types III/I collagen ratio in Dupuytren's contracture. These results suggest that a genetic defect in collagen production is unlikely and that the important phenomenon is an increase in fibroblast density.

Collagen↗
PubMed1991

The haemodynamic effects of bronchoscopy. Comparison of propofol and thiopentone with and without alfentanil pretreatment.

The haemodynamic response to bronchoscopy under general anaesthesia was investigated. Forty patients were allocated at random to receive either thiopentone or propofol; half the patients in each group received in addition 18 micrograms/kg of alfentanil one minute before induction of anaesthesia. The heart rate, noninvasive blood pressure and Holter ECG was monitored in all patients. Significant increases in heart rate (p less than 0.05), systolic and diastolic arterial pressures (p less than 0.01) occurred in the thiopentone only group, following bronchoscopy. Systolic and diastolic arterial pressure decreased in patients receiving thiopentone plus alfentanil, following induction of anaesthesia and laryngoscopy (p less than 0.05). No significant haemodynamic changes were seen in either of the groups which received propofol. ST segment changes on subsequent Holter analysis were seen in four patients, but there were no significant differences between the groups. Anaesthesia with propofol alone provides adequate haemodynamic stability for bronchoscopy and the addition is superfluous.

Aged↗
PubMed1991

Mutant p53, EGF receptor and c-erbB-2 expression in human breast cancer.

p53 expression was studied in 111 primary breast cancers with a monoclonal antibody (PAb240) that reacts with an epitope in mutant p53. Epidermal growth factor receptors (EGFr) and oestrogen receptors (ER) measured by ligand binding, c-erbB-2 expression assessed by immunochemistry and lymph node status were compared with p53 staining. Fifty-nine tumours (53%) were positive for p53, and this correlated with EGFr expression (P less than 0.02), which is a known poor prognostic factor. Eighteen out of 59 p53+ tumours expressed c-erbB-2 versus 4 out of 52 p53- tumours assessed on paraffin sections. However, assessing c-erbB-2 by Southern blotting and immunochemistry on frozen sections showed that 20 out of 59 p53+ tumours overexpressed or had amplified c-erbB-2 compared with 15 out of 52 p53- tumours (not significant). Mean EGFr concentration in p53+ tumours was 31 fmol per mg of membrane protein versus 14 fmol mg-1 in p53- tumours. Cytoplasmic staining was the most frequent pattern found for p53, but some cases showed cytoplasmic plus nuclear staining, or focal cells with predominantly nuclear staining. Thus, abnormal p53 is the commonest oncogene abnormality described in breast cancer. The association with EGFr expression suggests that these oncogenes interact in the pathogenesis of breast cancer.

Biomarkers, Tumor↗
PubMed1990

Modulation of fibroblast proliferation by oxygen free radicals.

The major unexplained phenomenon in fibrotic conditions is an increase in replicating fibroblasts. In this report we present evidence that oxygen free radicals can both stimulate and inhibit proliferation of cultured human fibroblasts, and that fibroblasts themselves release superoxide (O2.-) free radicals. Fibroblasts released O2.- in concentrations which stimulated proliferation, a finding confirmed by a dose-dependent inhibition of proliferation by free radical scavengers. Oxygen free radicals released by a host of agents may thus provide a very fast, specific and sensitive trigger for fibroblast proliferation. Prolonged stimulation may result in fibrosis, and agents which inhibit free radical release may have a role in the prevention of fibrosis.

Cell Division↗
PubMed1990

Carbon dioxide monitoring during high frequency jet ventilation for direct laryngoscopy.

To improve ventilation monitoring during direct laryngoscopy, we have developed a high frequency jet ventilator which allows the aspiration of tracheal gas for carbon dioxide analysis (PtCO2) through the injector after stopping the ventilator. In 41 patients undergoing direct laryngoscopy, PaCO2 and PtCO2 were measured simultaneously during high frequency jet ventilation under general anaesthesia. PtCO2 and PaCO2 correlated significantly (r = 0.88), but PtCO2 underestimated PaCO2 by 0.84 (SD 0.72) kPa. The arterial to tracheal PCO2 difference was influenced by airway obstruction.

Anesthesia, General↗
PubMed1988

Cocaine absorption from the nasal mucosa.

The absorption of cocaine from the nasal mucosa was measured by serial plasma analysis in patients who received nasal cocaine for routine nasal surgery using the modified Moffett's method. Two groups were compared: one received cocaine alone and one with adrenaline 1:1000 added. Changes in pulse rate and blood pressure were recorded in each group. The group that received intranasal cocaine and adrenaline solution had significantly lower plasma cocaine levels. There was no significant difference in cardiovascular parameters between the two groups.

Absorption↗
PubMed1987

Free radicals and Dupuytren's contracture.

The concentration of substrate expressed as hypoxanthine capable of reacting with xanthine oxidase to release superoxide free radicals (O2-) was measured in control and Dupuytren's contracture palmar fascia. In Dupuytren's contracture palmar fascia the concentration of hypoxanthine was six times that of control and was greatest in "nodular" areas. Xanthine oxidase activity was also detected in Dupuytren's contracture palmar fascia. These results suggest a greater potential for hypoxanthine-xanthine oxidase generated oxygen free radical formation in Dupuytren's contracture than in control palmar fascia. Production of free radicals may be an important factor in the pathogenesis of Dupuytren's contracture. The benefit of allopurinol in the management of Dupuytren's contracture and other fibrotic conditions may thus be explained, as allopurinol binds to xanthine oxidase and prevents release of free radicals.

Aged↗
PubMed1987

Basophil histamine release. A study in allergy to suxamethonium.

A patient who suffered a severe hypotensive episode after induction of anaesthesia, was subsequently found to show positive skin-test responses to suxamethonium. Investigation revealed that suxamethonium induced basophils from the patient to release histamine to an extent comparable to that found after exposure to anit-IgE. Basophils from control subjects showed no such response. Basophil histamine release may offer a useful approach to the investigation of adverse drug reactions.

Adult↗
PubMed1986

Chlormethiazole in the management of post-craniotomy seizures.

Epilepsy is an important problem in the period immediately following intracranial surgery. Rapid control of seizures is important to prevent damage to cerebral neuronal function. A method of managing epilepsy using intravenous chlormethiazole is reported. This regimen has proved to be safe and rapidly effective in the control of post-operative seizures.

Brain Diseases↗