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Biomedical subjects

R M Jones

Publications and source records attributed to R M Jones.

At least 91 records · Page 5Linked to original sources
PubMed1996

Sevoflurane degradation by soda lime in a circle breathing system.

Sevoflurane is degraded by soda lime to a vinyl ether commonly referred to as compound A. We measured the concentration of compound A in the circle breathing system of 31 patients receiving sevoflurane anaesthesia. Inspiratory and expiratory gas samples were analysed using gas chromatography and flame ionisation detection. The end-tidal sevoflurane concentration and soda lime temperature were recorded. The peak compound A concentration ranged between 10 to 32 ppm in the inspiratory limb and 7 to 26 ppm in the expiratory limb. There was a positive correlation between the peak compound A concentration and the end-tidal sevoflurane concentration (r2 = 0.545, p < 0.0001) and the soda lime temperature (r2 = 0.301, p = 0.0014). We conclude that the end-tidal concentration of sevoflurane and the temperature of the soda lime are important variables in determining concentration of compound A in a circle system.

Adult↗
PubMed1996

Biliary complications after liver transplant: the Victorian experience.

BACKGROUND: Biliary complications remain a continuing problem in liver transplantation. The goals of this study were to document the frequency of biliary complications following orthotopic liver transplantation in the Victorian programme, and to examine associations with suspected risk factors with reference to biliary stenosis. METHODS: Data were collected from 129 consecutive transplants in 123 patients (106 adults, 17 children) at the Austin Hospital, Melbourne during the period 1988-94. The 2 year actuarial survival was 88%. Biliary reconstruction was by end-to-end anastomosis in 89 patients and Roux-en-Y in 40. Complications were suspected on clinical, biochemical or microbiological evidence. Biliary stenoses were considered to be radiological evidence of duct narrowing. RESULTS: Biliary complications occurred in 19% and biliary stenosis in 8.5%. Of the stenoses, 1/35 occurred in the first 20 month period, 9/47 in the second and 1/47 in the third. There was a significant difference between the middle period and other periods (P<0.05, Chi-square test). This change may be related to incomplete flushing of bile from the donor liver. Recurrence of the original disease was suspected for one stenosis. The length of the donor bile duct from hilum to anastomosis, cold ischaemia time and total hepatic artery flow at transplant did not relate to stenosis. Cholangitis was not diagnosed in patients without strictures. Strictures were managed by dilatation (5/11) and by operative repair (6). CONCLUSIONS: Stenoses were not related to the length of the donor bile duct, cold ischaemia time or total hepatic artery flow. Meticulous adherence to the protocol for flushing out bile at the donor operation was associated with a significant reduction in frequency of biliary stenoses.

Actuarial Analysis↗
PubMed1996

An essential E box in the promoter of the gene encoding the mRNA cap-binding protein (eukaryotic initiation factor 4E) is a target for activation by c-myc.

The mRNA cap-binding protein (eukaryotic initiation factor 4E [eIF4E]) binds the m7 GpppN cap on mRNA, thereby initiating translation. eIF4E is essential and rate limiting for protein synthesis. Overexpression of eIF4E transforms cells, and mutations in eIF4E arrest cells in G, in cdc33 mutants. In this work, we identified the promoter region of the gene encoding eIF4E, because we previously identified eIF4E as a potential myc-regulated gene. In support of our previous data, a minimal, functional, 403-nucleotide promoter region of eIF4E was found to contain CACGTG E box repeats, and this core eIF4E promoter was myc responsive in cotransfections with c-myc. A direct role for myc in activating the eIF4E promoter was demonstrated by cotransfections with two dominant negative mutants of c-myc (MycdeltaTAD and MycdeltaBR) which equally suppressed promoter function. Furthermore, electrophoretic mobility shift assays demonstrated quantitative binding to the E box motifs that correlated with myc levels in the electrophoretic mobility shift assay extracts; supershift assays demonstrated max and USF binding to the same motif. cis mutations in the core or flank of the eIF4E E box simultaneously altered myc-max and USF binding and inactivated the promoter. Indeed, mutations of this E box inactivated the promoter in all cells tested, suggesting it is essential for expression of eIF4E. Furthermore, the GGCCACGTG(A/T)C(C/G) sequence is shared with other in vivo targets for c-myc, but unlike other targets, it is located in the immediate promoter region. Its critical function in the eIF4E promoter coupled with the known functional significance of eIF4E in growth regulation makes it a particularly interesting target for c-myc regulation.

Animals↗
PubMed1996

[Toxicology and clinical significance of base-catalized degradation of sevoflurane to Compound A].

Sevoflurane breaks down in basic environments to form a vinyl ether known as Compound A. This compound is toxic in the rat, with an LC50 of about 400 ppm after 3 h exposure and with renal damage evident between 50 and 100 ppm. There is no valid current evidence that Compound A is toxic in man, and the rat may not be an appropriate model for determination of this breakdown product's toxic potential in humans. The main factors influencing the degree of patient exposure to Compound A include fresh gas flow, sevoflurane concentrations, absorber temperature and composition, and the patient's carbon dioxide production.

Anesthetics, Inhalation↗
PubMed1996

Field evaluation of doramectin for treatment of gastrointestinal nematode infections and louse infestations of cattle.

OBJECTIVE: To evaluate the safety and efficacy of doramectin given by injection at a dosage of 200 micrograms/kg of body weight for treatment of gastrointestinal nematodiasis or louse infestations of cattle. ANIMALS: 1,031 mixed-breed cattle were treated in the nematode study and 418 were treated in the louse study. PROCEDURE: Naturally parasitized cattle were given 200 micrograms of doramectin/kg or an equivalent volume of saline solution, SC. In nematode experiments, fecal samples were collected from each animal 1 week before treatment, at time of treatment, and at weekly intervals there after for 3 weeks. In louse experiments, louse counts were carried out for each animal on the day of treatment and 14 and 28 days later. All cattle were weighted at the time of treatment and at the end of the experiment. RESULTS: By 21 days after doramectin treatment, fecal egg counts had decreased to zero in 9 of 10 experiments and to 1 egg/g in the remaining experiment. Differences between treatment groups were significant (P < 0.0001) in all instances. Pretreatment coproculture identified Haemonchus, Ostertagia, Cooperia, Trichostrongylus, and Nematrodirus as the represented genera. Doramectin was 100% effective in eliminating infestation with Linogna thus vituli, Haematopinus eurysternus, and Solenopotes capillatus. Infestation with the chewing louse Damalinia bovis was reduced overall by 86%. For all species, post treatment louse counts were significantly (P < 0.02) less for doramectin-treated cattle than for controls. Adverse reactions to doramectin were not apparent in either study. CONCLUSION AND CLINICAL RELEVANCE: Injectable doramectin at a dosage of 200 micrograms/kg is safe and effective for treatment of gastrointestinal nematodiasis and louse infestations of cattle under field conditions.

Animals↗
PubMed1995

Prazosin reduces myocardial ischemia/reperfusion-induced Ca2+ overloading in rat heart by inhibiting phosphoinositide signaling.

The aim of this study was to establish whether or not alpha 1-adrenergic receptors are implicated in triggering phosphoinositide hydrolysis and intracellular Ca2+ accumulation during myocardial ischemia and reperfusion. In isolated perfused rat hearts, the selective alpha 1-receptor antagonist prazosin abolished the increase in radioactivity incorporation into cellular inositol phosphates induced by 30 min ischemia followed by 30 min reperfusion, and selectively blocked the degradation of phosphoinositides; only minor changes in the ischemia/reperfusion-induced loss of other classes of phospholipids were seen. In addition, a prazosin-induced decrease of ischemia/reperfusion Ca2+ overloading was documented in real-time recordings of epicardial cytosolic free Ca2+ in fura 2-loaded hearts. An inhibition of early ischemic Ca2+ rise was observed, as well as a lower peak of cytosolic free Ca2+ and a more rapid reversal to normal values during reperfusion. Moreover, alpha 1-adrenergic blockade resulted in a significant improvement in the recovery of myocardial function during reperfusion: an increased left ventricular developed pressure and maximum rate of rise of systolic pressure paralleled the decrease in time-averaged cytosolic Ca2+ and the increase in amplitude of Ca2+ transients, respectively. It is concluded that myocardial Ca2+ overloading during ischemia and reperfusion may be triggered by alpha 1-adrenergic receptor-induced polyphosphoinositide hydrolysis.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1995

Urinary porphyrin profiles by laser desorption/ionization time-of-flight mass spectrometry without the use of classical matrices.

A method is described for the rapid analysis of mixtures of porphyrin methyl esters using laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS). Ions corresponding to [M+H]+ for each component have been observed without the need for added matrix. LDI-TOF MS has been applied to the analysis and characterization of porphyrin methyl esters derived from urine samples of patients suffering from various porphyrias. This technique has been shown to provide "fingerprint" profiles of the porphyrins present in each urine sample, characteristic of the porphyria, which compare favourably with those obtained with the established method of high-performance liquid chromatography. LDI-TOF MS is a rapid and reliable method for the screening of urine from patients suffering from porphyria.

Chromatography, High Pressure Liquid↗
PubMed1995

Peroxidase activation of tamoxifen and toremifene resulting in DNA damage and covalently bound protein adducts.

When [14C]tamoxifen was incubated with horseradish peroxidase and H2O2, two major metabolites, separated and identified by HPLC, were N-desmethyltamoxifen and tamoxifen N-oxide. Toremifene incubated in a similar system yielded N-desmethyltoremifene and toremifene N-oxide. No 4-hydroxylated metabolites were detected with either drug. When calf thymus DNA was included in peroxidase incubation mixtures, DNA damage, as assessed by 32P-postlabelling, could also be detected. The extent of damage caused by tamoxifen and toremifene was similar. The major adducts formed following incubation of DNA with tamoxifen had similar Rf values to two of the 32P-postlabelled adducts seen following dosing of rats with tamoxifen. Peroxidase was able to activate both drugs to derivatives which covalently bound to bovine serum albumin. The pH optimum for covalent binding and N-demethylation was near to pH 6.0. Results from liquid chromatography-electrospray secondary ion mass spectrometry suggest that tamoxifen and toremifene are metabolized by peroxidase to putative reactive epoxide intermediates responsible for the genotoxic effects. It is proposed that peroxidase oxidizes tamoxifen to a carbon-centred free radical which reacts with oxygen to form peroxy radicals capable of inserting an oxygen atom into tamoxifen. Lactoperoxidase and prostaglandin synthase are also able to catalyse tamoxifen N-demethylation and binding to protein. These data show that peroxidase can activate both tamoxifen and toremifene to an intermediate(s) that can damage DNA and covalently react with protein. Since it is known that women treated with tamoxifen can develop endometrial tumours, it may be relevant to determine whether activation of tamoxifen by peroxidases may contribute to its carcinogenic action at extrahepatic sites.

Animals↗
PubMed1995

Serum fluoride concentration and urine osmolality after enflurane and sevoflurane anesthesia in male volunteers.

The purpose of this study was to measure the serum fluoride concentration after enflurane or sevoflurane anesthesia and to compare the effects of prolonged anesthesia with these drugs on renal concentrating function in male volunteers. The study was subdivided into three stages; an ascending dose study of 3.0 and 6.0 minimum alveolar anesthetic concentration (MAC) hours of sevoflurane alone, a 6.0-MAC-hour comparison of enflurane and sevoflurane, and a 9.0-MAC-hour comparison of enflurane and sevoflurane. Renal concentrating function was assessed by an 18-h period of fluid deprivation and the serum fluoride concentration was measured at intervals until 60 h postanesthesia. The maximum serum fluoride concentration was greater in the volunteers exposed to sevoflurane and reached a peak in the 9-MAC-hour sevoflurane group of 36.6 microM (SD 4.3) compared with 27.5 microM (SD 2.6) in the 9-MAC-hour enflurane group. However, the rapid decrease in the serum fluoride concentration after sevoflurane was such that there was no difference between the areas under the fluoride concentration-time curves. There were no significant differences between the median maximum urine osmolalities after enflurane or sevoflurane anesthesia. Prolonged anesthesia with enflurane or sevoflurane is not associated with impaired renal concentrating function despite an increase in the serum fluoride concentration.

Adolescent↗
PubMed1995

Comparison of ondansetron and droperidol in reducing postoperative nausea and vomiting associated with patient-controlled analgesia.

In a randomised, placebo-controlled trial we have compared the efficacy of ondansetron and droperidol in reducing postoperative nausea and vomiting associated with patient-controlled analgesia after orthopaedic surgery. One hundred and forty five patients, ASA 1 and 2, undergoing major orthopaedic surgery were anaesthetised using a standardised technique. They were randomly allocated to receive patient-controlled analgesia as morphine 1 mg.ml-1 alone; morphine as before plus a single dose of 1.25 mg droperidol together with 0.083 mg.ml-1 in the infusion syringe; or morphine as before plus 4 mg ondansetron and 0.13 mg.ml-1 in the syringe. The patient-controlled analgesia bolus dose was set at 1 ml with a 5 min lockout and a 4 h maximum dose of 30 mg morphine. There was no background infusion. The occurrence of nausea, vomiting and sedation was assessed every 4 h. The incidence of vomiting decreased from 59% in the morphine-only group to 35% and 14% in the droperidol (p < 0.05) and ondansetron groups (p < 0.001) respectively. The number of patients suffering from nausea alone was not significantly different between the three groups, although those in the ondansetron group experienced less severe nausea (p < 0.05) when using a two point scale. The droperidol group had significantly higher sedation scores than the other two groups (p < 0.005). We conclude that ondansetron is superior to droperidol when used with patient-controlled analgesia and causes less sedation.

Adolescent↗
PubMed1995

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↗
PubMed1995

Is there a need for a new inhalational anaesthetic agent?

New anaesthetic agents are continually being developed in an effort to prepare the ideal agent. Isoflurane is the first choice of many anaesthetists, although it clearly falls short of the ideal on a number of counts. The need and place for any new agent depends on comparing the properties of a theoretically ideal agent with those of isoflurane and the new agent. Desflurane is a step towards a more ideal inhaled agent; however, there is still the need to synthesise and evaluate new chemical entities in order that the ideal can more nearly be approached.

Anesthesia, Inhalation↗
PubMed1995

Pharmacokinetics and bioequivalence of parenterally administered doramectin in cattle.

Plasma concentrations of doramectin in 40 cattle dosed by subcutaneous (sc) or intramuscular (i.m.) injection (200 micrograms/kg) were compared to assess the bioequivalence of the two routes of administration. Peak concentration (Cmax), and areas under the concentration curve (AUC0-infinity) were determined from plasma concentrations. Animals treated by the sc route showed a mean AUC0-infinity of 457 +/- 66 ng.day/mL (+/- SD) and a mean Cmax of 27.8 +/- 7.9 ng/mL. Results from the i.m. treatment group showed a mean AUC0-infinity of 475 +/- 82 ng.day/mL and a mean Cmax of 33.1 +/- 9.0 ng/mL. Absorption constants (ka) determined by modelling were 0.542 +/- 0.336 day-1 after sc administration and 0.710 +/- 0.357 day-1 after i.m. administration. The 90% confidence limits on the difference between mean AUC0-infinity values for the sc and i.m. groups fell within 20% of the mean value for the subcutaneous group. Cmax was somewhat greater for the i.m. route. The 90% confidence limits on the difference in mean In(Tmax +1) also fell within 20% of the mean sc value. Based on this analysis, bioequivalence of the sc and i.m. formulation has been established.

Absorption↗
PubMed1995

Mivacurium in special patient groups.

In special patient groups, drug response may be different from that in the healthy adult patient. Mivacurium dose requirements vary with age, and children require larger doses to obtain any given degree of block, but the elderly often require smaller doses. However, the dose requirements of the neonate do not necessarily differ greatly from those of the adult. There is a relationship between the duration of action of a bolus dose as well as infusion requirements to maintain block and the plasma cholinesterase activity. Patients with renal disease may have a decreased cholinesterase activity and may require smaller doses of mivacurium. Patients with severe liver disease may have a marked decrease in cholinesterase activity, and in these patients a substantially smaller dose of the drug may be needed to obtain and maintain any given degree of block. If the variation in dose requirements is kept in mind and the degree of block appropriately monitored, mivacurium may be used with safety in special patient groups, such as children, the elderly, or those with renal or hepatic impairment.

Adult↗
PubMed1995

Hepatitis B virus precore mutant infection is associated with severe recurrent disease after liver transplantation.

The factors that predispose patients undergoing liver transplantation for hepatitis B virus (HBV) disease to severe recurrence of infection are unclear. In this study we examined the effect of pretransplantation infection with HBV and precore variant strains of HBV on posttransplantation outcome and allograft histology in 24 patients who survived more than 3 months after liver transplantation. Based on pretransplantation serum HBV DNA status as detected by the polymerase chain reaction (PCR) and direct sequencing, the 24 patients could be assigned to three groups. In group 1 there were 4 patients HBV DNA-negative before transplantation and none of these patients suffered recurrence of infection posttransplantation. In group 2, of 10 patients with pretransplantation infection with wild-type virus, 7 became reinfected, and 1 of these developed HBV-related graft failure. In group 3, 9 of 10 patients infected with precore mutant HBV strains became reinfected. However, in contrast to the patients in group 2, 7 patients in group 3 developed HBV-related graft loss, and 5 of these patients had fibrosing cholestatic hepatitis (FCH). These results indicate that infection with precore mutant strains of HBV predisposes a patient to early graft loss following transplantation.

Cholestasis↗
PubMed1994

Lymphoproliferative disease of donor origin arising in patients after orthotopic liver transplantation.

BACKGROUND: Lymphoproliferative disease is a well recognized complication of organ transplantation and in many cases is associated with Epstein-Barr virus (EBV) infection. It is widely though that posttransplantation lymphoproliferative disease (PTLPD) arises from recipient lymphoid cells. However, solid organ allografts are likely to include donor lymphoid tissue around or within the transplanted organ. Therefore, it is possible that transplanted donor lymphocytes may proliferate to form PTLPD: METHODS: The genetic origin of tumor cells was determined by microsatellite DNA fingerprinting using the polymerase chain reaction (PCR). Their EBV association and clonality were established by PCR amplification of DNA extracted from formalin fixed, paraffin embedded tissue using primers to conserved regions of the EBV genome and the immunoglobulin heavy chain gene, respectively. RESULTS: The authors have demonstrated two cases of lymphoproliferative disease that were derived from donor lymphocytes in orthotopic liver transplant recipients. In both cases, the proliferating cells were EBV DNA positive. Furthermore, the PTLPD was restricted to allograft tissue around the porta hepatis. However, the two cases differed in their clonal properties and response to treatment: one case was oligoclonal and regressed after antiviral therapy and a modest reduction of immunosuppression, whereas the other contained two clonal populations and was controlled only after treatment with antineoplastic chemotherapy. CONCLUSION: This study has demonstrated two cases of PTLPD that were derived from donor lymphoid tissue. Although both cases were associated with EBV and remained localized to allograft tissue, their clonality and response to therapy differed.

Adult↗