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Biomedical subjects

A McCluskey

Publications and source records attributed to A McCluskey.

At least 37 records · Page 2Linked to original sources
PubMed2000

Anhydride modified cantharidin analogues: synthesis, inhibition of protein phosphatases 1 and 2A and anticancer activity.

Two series of anhydride modified cantharidin analogues were synthesised and screened for their phosphatase inhibition (PP1 and PP2A) and cytotoxicity in various cancer cell lines (Ovarian A2780, ADDP; Osteosarcoma 143B; and Colon HCT116 and HT29). One series was synthesised by a novel, high yielding one-pot hydrogenation-ring-opening-esterification procedure, the other by acid catalysed acetal formation. Analogues 5-7 and 9 displayed moderate PP2A selectivity (ca. 5- to 20-fold) and inhibition typically in the low microM range (comparable, in some cases to cantharidin). The anticancer activity of these analogues varied with the cell line under study; however, many of them showed selective cytotoxicity for the colon tumour cell lines.

Anhydrides↗
PubMed2000

A gene therapy approach to enhance the targeted radiotherapy of neuroblastoma.

BACKGROUND: The aims of this study were to determine whether the introduction and expression of the noradrenaline transporter (NAT) gene into NAT-negative neuroblastoma cell lines would make them amenable to targeted radiotherapy using [(131)I]MIBG. PROCEDURE: Neuroblastoma cell lines were transfected with a eukaryotic expression vector containing the bovine noradrenaline transporter cDNA under the expression of the CMV promoter. Stable transfectants were created by selection in geneticin (G418) and were characterised for their MIBG uptake ability and susceptibility to [(131)I]MIBG therapy. RESULTS: The cell line SK-N-MC, which normally shows no ability to take up MIBG, was successfully transfected with bNAT. SK-N-MC.bNAT transfectants exhibited uptake and release kinetics similar to those of the natural NAT-expressing cell line SK-N-BE(2c). Levels of [(131)I]MIBG uptake were 33% of those of the highest naturally NAT-expressing cell line SK-N-BE(2c). Growth delay assays using multicellular spheroids indicated that this degree of [(131)I]MIBG uptake was sufficient to inhibit growth at radioactive concentrations of 4 Mbq/ml. CONCLUSIONS: These results demonstrate the feasibility of combining gene therapy with targeted radiotherapy to enhance uptake, and hence radiation dose, to neuroblastoma tumours using [(131)I]MIBG. With the appropriate delivery vehicle and tumour-specific control of expression, the introduction of noradrenaline transporter molecules may be a viable means of enhancing the response of neuroblastoma tumours to [(131)I]MIBG therapy.

Carrier Proteins↗
PubMed2000

Corticotropin releasing hormone: therapeutic implications and medicinal chemistry developments.

Corticotropin releasing hormone (CRH, sometimes known as CRF) is an endogenous 41 amino acid peptide that has been implicated in the onset of pregnancy, the 'fight or flight' response, in addition to a large number of physiological disorders. Recently, medicinal chemists have developed a number of potent and selective compounds that show promise in a vast array of therapeutic uses. Herein we review the current status of research.

Amino Acid Sequence↗
PubMed2000

Inspiratory vocal cord dysfunction, a new approach in treatment.

Vocal cord dysfunction is a well recognized respiratory condition in which adduction of the vocal cords during either inspiration or expiration, or both, causes functional airways obstruction. Diagnosis is usually made by laryngofibreoscopy, however treatment of this condition has generally been unsatisfactory, requiring a multi-disciplinary approach consisting of speech therapy, psychological counselling, sedatives and anaesthetic agents. Here we use an innovative approach which requires relatively inexpensive and simple anaesthetic equipment in order to manipulate airways resistance and thus reduce any vocal cord dysfunction as it occurs. The patient involved found instant relief when using this simple device which is easy to use and is portable.

Adult↗
PubMed2000

Paid attendant carers hold important and unexpected roles which contribute to the lives of people with brain injury.

OBJECTIVE: Paid attendant carers spend many hours assisting people with a brain injury. Despite this considerable responsibility, most carers receive little support or training and their roles are often ill-defined. This exploratory study set out to define the key roles of paid carers. METHOD: Ten semi-structured interviews were conducted. Perspectives were sought from 10 participants: five people with a traumatic brain injury and five paid carers. A computer software package, NUD*IST was used during analysis to help identifvy and categorize commonly recurring themes. RESULTS: Five major roles were identified: Attendant, Protector, Friend, Coach and Negotiator. Friendship was the most important aspect of the care relationship for three of the people with a brain injury, most of whom had lost their pre-injury friends and associates. Carers were required to negotiate frequently with clients and their families, and with other service providers. Sound communication skills were required. CONCLUSION: In addition to further research, industry guidelines are required which take account of the wider suite of roles fulfilled by paid carers, address training and support needs, and occupational health and safety issues.

Adult↗
PubMed2000

A dose-ranging study of rapacuronium in pediatric patients.

BACKGROUND: The aim of this study was to determine the dose or doses of the new rapid-onset, short-acting, neuromuscular blocking drug rapacuronium that would provide satisfactory conditions for tracheal intubation at 60 s in infants and children. METHODS: Sixty-five infants (< 1 yr), 51 younger children (1-6 yr), and 49 older children (7-12 yr) were studied. Anesthesia was induced with thiopental-nitrous oxide-oxygen. Tracheal intubation was attempted 60 s after administration of one of five doses of rapacuronium (0.5, 1.0, 1.5, 2.0, or 2.5 mg/kg) and intubating conditions were assessed using a four-point scale. Following tracheal intubation, anesthesia was maintained with nitrous oxide-oxygen and alfentanil (12.5-50 microg/kg) as necessary. Neuromuscular transmission was monitored in an uncalibrated fashion using an acceleromyograph. RESULTS: Intubating conditions were good or excellent at 60 s in all infants after doses of 1.5 mg/kg or more and in all younger and older children after doses of 2.0 mg/kg or more. The duration of action of rapacuronium was dose- and age-dependent. Mean times to reappearance of the third twitch of the train-of-four (TOF; T3) were less than 10 min in infants at doses of 1.5 mg/kg or less and in younger and older children at doses of 2.0 mg/kg or less. Recovery of T3 after 1.0-2.0 mg/kg rapacuronium was significantly slower in infants compared with younger (P = 0.001) and older (P = 0.02) children. Five adverse experiences were related to rapacuronium administration: Bronchospasm (two instances), tachycardia (one instance), and increased salivation (two instances). None were serious. CONCLUSIONS: Doses of 1.5 and 2.0 mg/kg rapacuronium can produce satisfactory intubating conditions at 60 s in anesthetized infants and children, respectively, and are associated with a short duration of action.

Age Factors↗
PubMed2000

Service utilization following traumatic brain injury.

OBJECTIVES: To document service utilization by people with a traumatic brain injury at different times postinjury and to identify factors that predict service use. DESIGN: Cross-sectional study design. Four groups of subjects were randomly selected from a regional database, according to their time postinjury: 6-18 months; 2-4 years; 6-9 years; and 10-17 years. SUBJECTS: A total of 119 adults with a traumatic brain injury (TBI). SETTING: Hospital and community-based clients in Sydney, Australia. OUTCOME MEASURES: Glasgow Outcome Scale, Disability Rating Scale; Functional Independence Measure; Lidcombe Psychosocial Disability Scale; number, type, and frequency of services used in the previous 12 months. RESULTS: Subjects in all four groups used a variety of services. The mean number of services used was 4.2, and there was only a moderate decline in service use over time. The use of medical and allied health services remained high in all four groups. Severity of injury, physical and cognitive disability, and psychosocial disability were all predictors of service utilization. Psychosocial disability was strongly associated with ongoing service utilization. CONCLUSION: In this study, people with TBI used services well beyond the early stage of recovery. Psychosocial disability may be a better predictor of service use than physical and cognitive disability alone.

Activities of Daily Living↗
PubMed1999

Pharmacophore development for corticotropin-releasing hormone: new insights into inhibitor activity.

Corticotropin-releasing hormone (CRH) is an endogenous 41-amino acid peptide involved in a wide ranging series of systems including the brain, the coordination of the body's overall response to stress, and more recently as a crucial initiator in the onset of labor, also known as the placental clock. Although more physiological data on CRH is emerging shedding more light on the processes involved and their integration, the mode of action of the hormone and the postulated binding site(s) remain unknown. Recently, a number of small-molecular-weight ligands have emerged as potent antagonists but, as therapeutics, suffer from a lack of solubility. Additionally, despite a number of exhaustively large patents, the lack of structural diversity with these antagonists has enabled little scope for comprehensive and wide ranging studies into the structure of the binding sites of this hormone. As part of a program investigating new, structurally diverse antagonists and agonists of CRH, we have developed a preliminary pharmacophore based on the known small-molecular-weight ligands as an initial step in our program. This pharmacophore was validated by comparison with some of the compounds we postulated to be active.

Adrenocorticotropic Hormone↗
PubMed1999

Effective time to satisfactory intubation conditions after administration of rocuronium in adults. Comparison of propofol and thiopentone for rapid sequence induction of anaesthesia.

We determined the effective time to satisfactory intubation conditions after the administration of rocuronium 0.6 mg.kg-1 to 120 unpremedicated adult patients anaesthetised with propofol 2.5 mg.kg-1 or thiopentone 5 mg.kg-1. Intubation conditions were assessed in 10 subgroups of 12 patients at 30, 40, 50, 60 and 70 s. The effective times to satisfactory intubation conditions in 50 and 90% of patients were obtained by the method of maximum likelihood after log time-probit response transformations. Intubation conditions after induction of anaesthesia with propofol were satisfactory in 5/12 patients at 30 s, 7/12 at 40 s, 10/12 at 50 s, 11/12 at 60 s and 11/12 at 70 s compared with 1/12 patients at 30 s, 2/12 at 40 s, 5/12 at 50 s, 7/12 at 60 s and 8/12 at 70 s after induction with thiopentone. The effective times to satisfactory intubation conditions in 50% and 90% (95% confidence intervals) of patients after rocuronium 0.6 mg.kg-1 were 34 (26-40) s and 61 (50-81) s in patients given propofol compared with 57 (48-69) s and 101 (79-167) s in patients given thiopentone. We conclude that rocuronium 0.6 mg.kg-1 may be a suitable alternative to suxamethonium during rapid sequence induction of anaesthesia with propofol in situations where suxamethonium is contraindicated.

Adolescent↗
PubMed1999

The analgesic efficacy of tramadol versus ketorolac in day-case laparoscopic sterilisation.

We conducted a prospective, randomised, double-blind study to compare the analgesic efficacy of intravenous tramadol 1.5 mg.kg-1 and ketorolac 10 mg in 60 ASA grade 1 and 2 patients scheduled to undergo day-case laparoscopic sterilisation by application of Filshie clips. Patients who received tramadol had significantly less postoperative pain in the recovery room (p = 0.007) and at discharge from the day-surgery unit (p = 0.03), and they required rescue analgesia with morphine less often (p = 0.02) than patients who received ketorolac. No difference in either the incidence or severity of nausea and vomiting was observed between the two groups. Both analgesic drugs were well tolerated at the doses given in the study, although dry mouth was significantly more common after the administration of tramadol (p = 0.009). Three patients in the tramadol group and five in the ketorolac group required overnight admission due to pain or nausea and vomiting.

Adult↗
PubMed1997

A comparison of acceleromyography and mechanomyography for determination of the dose-response curve of rocuronium in children.

In order to compare an acceleromyograph (TOF-Guard) with a mechanomyograph (Grass FT03), the dose-response relationship of rocuronium was simultaneously determined in both arms of 15 children aged 3-11 years during anaesthesia with thiopentone, alfentanil and nitrous oxide. Three subgroups of five children received rocuronium 120, 180 or 240 micrograms.kg-1 randomly. The effective doses to produce 50% and 95% depression of the first twitch of the train-of-four determined by acceleromyography were 206 and 337 micrograms.kg-1, respectively, while these values determined by mechanomyography were 151 and 331 micrograms.kg-1, respectively. The dose-response curve obtained by acceleromyography was steeper and shifted to the right compared with that obtained by mechanomyography (p < 0.0001). The difference between the effective dose producing 50% twitch depression determined by the two devices was highly significant (p < 0.0001). In 13 out of 15 children, the acceleromyograph control train-of-four ratio was significantly greater than unity. Although there was a good correlation (r = 0.85) between simultaneous pairs of measurements of neuromuscular block, the acceleromyograph exhibited a bias of -25% relative to the mechanomyograph with wide limits of agreement (-62 to +12%). We conclude that acceleromyographic and mechanomyographic measurements should not be used interchangeably when determining the potency of muscle relaxants.

Androstanols↗