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Biomedical subjects

E Doyle

Publications and source records attributed to E Doyle.

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

The impact of column temperature in the high performance liquid chromatographic analysis of topotecan in rat and dog plasma.

A sensitive high performance liquid chromatographic (HPLC) assay has been developed and validated for the quantitation of the novel anticancer agent topotecan and topotecan as its lactone plus carboxylate forms in rat and dog plasma. Linear responses in analyte standard peak areas were observed over the concentration ranges 0.10-10 ng ml-1 using 100 microliters of rat plasma and 0.2-100 ng ml-1 using 100 microliters of dog plasma. Due to the instability of the drug in the biological matrix it was necessary to obtain the plasma fraction within 5 min after blood sampling by centrifugation, immediately followed by protein precipitation with cold methanol (-30 degrees C). For the determination of total drug levels (lactone plus lactone ring-opened form), plasma samples were deproteinated with methanol and subsequently acidified with 2% (v/v) perchloric acid. The samples were analysed by HPLC using a Zorbax SB-C18 Stable Bond column and methanol-0.1 M hexane-1-sulfonic acid in methanol-0.01 M N,N,N'N'-tetramethylethylenediamine in distilled water pH 6.0 (25:10:65, v/v/v) as the mobile phase. The detection was performed fluorimetrically. The analytical column was thermostated at 19-21 degrees C to obtain baseline resolution between an interfering endogenous compound in rat and dog plasma and topotecan. This endogenous peak was absent in human plasma. Variation of chromatography temperature appeared to be a very useful tool in the bioanalysis of topotecan. It allowed optimization of the separation between the endogenous compound and the analyte; different mechanisms of solute interactions are apparently involved in this reversed-phase ion-pair chromatographic system.

Animals↗
PubMed1996

Comparison of i.v. and s.c. diamorphine infusions for the treatment of acute pain in children.

We have compared the i.v. and s.c. routes of administration for diamorphine infusions in children undergoing abdominal surgery. Subjects received general anaesthesia with extradural block and diamorphine up to 20 micrograms kg-1 h-1 after operation. There were no differences between the groups in diamorphine consumption, pain scores or incidence of side effects. The s.c. route appeared to be as effective and safe as the i.v. route for administration of diamorphine infusions in children undergoing elective surgery.

Abdomen↗
PubMed1996

Validation of three paediatric pain scores for use by parents.

Twenty children undergoing general surgery and 20 children undergoing otorhinolaryngological surgery were simultaneously assessed on two occasions by a doctor and a parent using three pain scoring systems. The pain scoring systems used were the Objective Pain Score, a four point numerical score and a 100 mm visual analogue scale. There was a high correlation between the scores given by the doctor and by the parents for all three scoring systems with parents consistently giving slightly higher scores than the doctor. The correlation coefficients for parental and medical pain scores in recovery were 0.77 for the Objective Pain Score, 0.70 for the four point numerical score and 0.69 for the visual analogue scale (p < 0.01). At 1 h after leaving the recovery area the correlation coefficients were 0.81, 0.80 and 0.73 respectively (p < 0.01). These results suggest that parental scoring of pain in children will be useful in future audit and research of analgesic regimens, particularly in day-case surgery.

Analgesics↗
PubMed1996

The optimal dose of ketamine for caudal epidural blockade in children.

Sixty boys aged up to 9 years undergoing orchidopexy were randomly allocated to receive one of three solutions for caudal epidural injection: group A received 1 ml.kg-1 of 0.25% bupivacaine with 0.25 mg.kg-1 of preservative-free ketamine, group B received 1 ml.kg-1 of 0.25% bupivacaine with ketamine 0.5 mg.kg-1 and group C received 1 ml.kg-1 of 0.25% bupivacaine with 1 mg.kg-1 of ketamine. Postoperative pain was assessed by means of a modified Objective Pain Score and analgesia was administered if this score exceeded four. The median duration of caudal analgesia was 7.9 h in group A, 11 h in group B and 16.5 h in group C. There were no differences between the groups in the incidence of motor block, urinary retention, postoperative vomiting or postoperative sedation. Group C had a significantly higher incidence of behavioural side effects, including slightly odd behaviour, vacant stares and abnormal effect than groups A and B.

Anesthesia, Caudal↗
PubMed1996

Proliferation indexes--a comparison between cutaneous basal and squamous cell carcinomas.

AIMS: To compare differences in cell proliferation indexes and apoptotic indexes between cutaneous basal and squamous cell carcinomas, in an attempt to suggest an explanation for the differences in their biological behaviour. METHODS: Forty cases of cutaneous basal cell carcinoma (BCC) and 40 cases of moderately and well differentiated squamous cell carcinoma (SCC) were retrieved from the archives. Sections, 4 microns thick, were cut from formalin fixed, paraffin wax embedded tissue in each case and stained with haematoxylin and eosin. These were then examined for mitotic and apoptotic figures per 1000 cells. Sections from the same cases were also immunostained with the mouse monoclonal antibody Ki67 (MIB1); positive nuclear staining was counted per 1000 cells. RESULTS: No significant differences were found between the mitotic indexes and apoptotic indexes in these tumours. There was, however, a significant difference in Ki67 (MIB1) staining, with greater staining in the squamous cell carcinomas. CONCLUSION: Estimation of the mitotic and apoptotic indexes did not reveal any differences between these two tumour types. The proliferation indexes, assessed by Ki67 immunostaining, did differ. This may be one of the factors underlying the more aggressive behaviour of SCC.

Apoptosis↗
PubMed1995

High-performance liquid chromatographic determination of the novel antitumour drug topotecan and topotecan as the total of the lactone plus carboxylate forms, in human plasma.

A sensitive high-performance liquid chromatographic (HPLC) assay has been developed and validated for the quantitation of the novel anticancer agent topotecan and topotecan as the total of its lactone and carboxylate forms in human plasma. Linear response in analyte standard peak area were observed over the concentration range 0.05-10 ng/ml using 100-microliters plasma samples. The instability of the drug in the biological matrix necessitated that the plasma fraction was obtained within 5 min after blood sampling by centrifugation, immediately followed by protein precipitation with cold methanol (-30 degrees C). Stability studies have indicated that topotecan is stable in these methanolic extracts for at least 4.5 months at -30 degrees C and 2 months at -70 degrees C. For the total determination of the lactone plus lactone ring-opened forms of the drug as topotecan, plasma samples were deproteinated with methanol and, subsequently, acidified with 7% (v/v) perchloric acid. Plasma samples for the measurement of total levels of the lactone and the ring-opened forms of topotecan were stable for at least 4.5 months when stored at -30 degrees C. After centrifugation, the supernatants were analysed by HPLC using a Zorbax SB-C18 Stable Bond column and methanol-0.1 M hexane-1-sulfonic acid in methanol-0.01 M N,N,N',N'-tetramethylethylenediamine (TEMED) in distilled water pH 6.0 (25:10:65, v/v) as the mobile phase. Detection was performed fluorimetrically. Within-run and between-run precision was always less than 12.1% in the concentration range of interest (0.05-10.0 ng/ml). The limit of quantitation is 0.05 ng/ml. Accuracy measurements ranged between 87.6 and 113.5%.

Antineoplastic Agents↗
PubMed1995

Determination of the polar drug dimiracetam in human plasma and serum by column-switching high-performance liquid chromatography.

A sensitive and fully automated column-switching HPLC method was developed for the determination of a novel cognition enhancer, dimiracetam, in human plasma and serum. A sample of plasma was ultrafiltered and then directly injected onto a first mu Bondapak C18 column. The sample was eluted with water. The portion of the eluate (heart-cut) from this column containing the drug was selected and loaded on a second mu Bondapak C18 column and eluted with water. During the elution of the second column, the first column was automatically rinsed with water-acetonitrile (50:50, v/v) and then equilibrated for a new injection. The total analysis time for each sample was 35 min. This corresponded to a 30% decrease in analysis time compared with the time that would have been needed with a simple run with two mu Bondapak C18 columns assembled in series. Ultraviolet detection at 200 nm was used to monitor the eluate. The method was fully validated over the quantitation range 27 ng/ml-15 micrograms/ml. The applicability of the method was demonstrated by analysis of serum samples from a study performed in human healthy volunteers.

Chromatography, High Pressure Liquid↗
PubMed1995

Analysis of unconjugated morphine, codeine, normorphine and morphine as glucuronides in small volumes of plasma from children.

A sensitive method for the analysis of unconjugated morphine, codeine, normorphine and total morphine after hydrolysis of glucuronide conjugates is described. The method was applicable to 50-microliters volumes of plasma. The analytes were converted to heptafluorobutyryl (HFB) derivatives before analysis by gas chromatography-negative ion chemical ionization mass spectrometry. Morphine and codeine were quantified against their [2H3]-isotopomers. Linearity, precision and accuracy were quite acceptable (in the 10(-10)-10(-9) g range), and the absolute limits of detection were < 1 pg.

Child↗
PubMed1995

Comparison of the effects of adrenaline, clonidine and ketamine on the duration of caudal analgesia produced by bupivacaine in children.

Sixty boys, aged 1-10 yr, undergoing orchidopexy were allocated randomly to receive one of three solutions for caudal extradural injection. Group A received 0.25% bupivacaine 1 ml kg-1 with adrenaline 5 micrograms ml-1 (1/200,000), group C received 0.25% bupivacaine 1 ml kg-1 with clonidine 2 micrograms kg-1 and group K received 0.25% bupivacaine 1 ml kg-1 with ketamine 0.5 mg kg-1. Postoperative pain was assessed using a modified objective pain score and analgesia was administered if this score exceeded 4. The median duration of caudal analgesia was 12.5 h in group K compared with 5.8 h in group C (P < 0.05) and 3.2 h in group A (P < 0.01). There were no differences between the groups in the incidence of motor block, urinary retention or postoperative sedation.

Analgesia↗
PubMed1995

Postoperative nausea and vomiting in paediatric surgical inpatients.

A prospective study of postoperative nausea and vomiting (PONV) was conducted in 415 children presenting for inpatient surgery. The overall incidence of PONV was 18.1%). The highest incidence was in children undergoing ENT procedures and increased with age. Avoidance of intraoperative opioids and the use of local anaesthesia and/or non-steroidal anti-inflammatory drugs reduced the incidence of nausea and vomiting postoperatively.

Analgesics, Opioid↗
PubMed1994

Prevention of postoperative nausea and vomiting with transdermal hyoscine in children using patient-controlled analgesia.

We have studied 40 children aged 6-14 yr undergoing abdominal surgery under general anaesthesia with extradural block; they were allocated randomly to receive transdermal hyoscine (loading dose 140 micrograms, followed by 5 micrograms h-1) or placebo for the duration of postoperative analgesia with PCA morphine. There was a significant (P < 0.001) reduction in the incidence of postoperative nausea and vomiting in the treated group compared with the placebo group during the first 48 h after operation. The treated group also had a significantly increased incidence of sedation (P < 0.02) and dry mouth (P < 0.01).

Administration, Cutaneous↗
PubMed1994

Comparison of different bolus doses of morphine for patient-controlled analgesia in children.

Forty children undergoing appendicectomy were allocated randomly to receive one of two PCA regimens with morphine. Group B10 received bolus doses of 10 micrograms kg-1 and group B20 received bolus doses of 20 micrograms kg-1. In both groups there was a lockout interval of 5 min and a background infusion of 4 micrograms kg-1 h-1. Group B20 self-administered considerably more morphine (P < 0.01) than group B10. There was no difference between the pain scores of the groups at rest. Group B20 had significantly (P < 0.05) smaller pain scores during movement than group B10 and the latter group suffered significantly (P < 0.01) more hypoxaemic episodes than group B20. There were no differences between the groups in the incidence of vomiting, excess sedation or the amount of time spent asleep at night.

Adolescent↗
PubMed1994

Comparison of patient-controlled analgesia in children by i.v. and s.c. routes of administration.

Sixty children undergoing appendicectomy were allocated randomly to receive one of two PCA regimens with morphine. Group IV received standard i.v. PCA with a bolus dose of morphine 20 micrograms kg-1 and a background infusion of 4 micrograms kg-1 h-1 while group SC received PCA by the s.c. route with a bolus dose of morphine 20 micrograms kg-1 and a background infusion of 5 micrograms kg-1 h-1. In both groups there was a lockout interval of 5 min. Group SC self-administered significantly less morphine (P < 0.05) and had a significantly (P < 0.01) greater percentage of valid demands for analgesia than group IV. There were no differences in pain scores between the groups at rest or during movement. Group IV suffered significantly (P < 0.01) more hypoxic episodes than group SC. There were no differences between groups in the incidence of postoperative nausea and vomiting or oversedation. S.c. PCA appears to be as effective and safe as i.v. PCA. By giving patients feedback on the occurrence of valid demands for analgesia, s.c. PCA may produce more appropriate and effective use of PCA.

Adolescent↗