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Biomedical subjects

R E Taylor

Publications and source records attributed to R E Taylor.

At least 19 recordsLinked to original sources
PubMed2007

Fatal pneumonitis in children with metastatic rhabdomyosarcoma following whole lung radiotherapy and sequential epirubicin.

Interstitial pneumonitis is a recognized complication following whole lung radiotherapy. We report two cases in which fatal pneumonitis appeared to be precipitated by the administration of epirubicin-containing combination chemotherapy within 7 weeks of completion of whole lung radiotherapy. These cases highlight a potentially fatal interaction between radiotherapy and modern chemotherapy regimens.

Antibiotics, Antineoplastic↗
PubMed2004

Outcome of patients with stage III or inoperable WT treated on the second United Kingdom WT protocol (UKWT2); a United Kingdom Children's Cancer Study Group (UKCCSG) study.

BACKGROUND: The aims of UKWT2 included consolidating the results for stage III patients obtained in UKWT1 and improving the outcome for patients with inoperable tumours by giving vincristine, actinomycin-D and doxorubicin in an intensive schedule (Intensive AVA). PROCEDURE: The second UK WT trial (UKWT2) ran between July 1986 and September 1991 accruing 448 patients. One hundred and six patients were diagnosed and treated for stage III disease. Six had clear cell sarcoma of the kidney (CCSK) and seven had rhabdoid tumours of the kidney (RTK) and are analysed separately. One other patient was excluded from overall analysis. Ninety-two patients were followed for a median of 115 months. Seventy-five received standard chemotherapy and abdominal radiotherapy according to protocol. Seventeen had stage III disease at immediate nephrectomy, but radiotherapy was omitted by physician choice. Thirty-three patients had inoperable disease at diagnosis and received pre-nephrectomy chemotherapy. RESULTS: Overall survival (OS) at 4 years for stage III favourable histology (FH) patients receiving abdominal RT was 83% (CI: 73-89). For children with stage III disease in whom RT was omitted the OS was 82% (CI: 59-97) and for inoperable disease 94% (CI: 78-98). The overall and event-free survival (EFS) of children with stage III CCSK was 100% and was achieved with the majority of patients not receiving radiotherapy (CI: 48-100). Three of seven children with RTK are alive EFS and OS 43% (CI: 10-73). For patients treated by abdominal radiotherapy the overall local control rate was 94.4% (CI: 86.4-98.5*%), 96.7% (CI: 88.5-99.6%) for flank RT and 83.3% (51.6-98.0%) for whole abdominal radiotherapy (WRT). CONCLUSIONS: The outcome for stage III FH disease was similar to that reported for UKWT1 and NWTS-3. The combination of abdominal RT together with 3-drug chemotherapy achieves a high abdominal tumour control rate. Flank RT is probably sufficient for localised tumour rupture. The high cure rates for children in this trial with 'inoperable disease' suggests that treatment should be modified according to their post-chemotherapy stage in order to avoid over-treatment. The high OS for stage III CCSK on this protocol suggests that treatment duration could be curtailed and the role of RT reviewed, though the numbers are small. The prognosis for older children with RTK seems to be better than for younger children although larger studies are required to confirm this.

Adolescent↗
PubMed2003

Proton radiotherapy for paediatric tumours: potential areas for clinical research.

Radiotherapy plays an important role in the management of children with cancer. The aim is to achieve local tumour control while minimizing long-term effects. In the treatment of tumours of the central nervous system (CNS) the most important long-term effects are neuropsychological. Elsewhere orthopaedic long-term effects may compromise function or be cosmetically harmful. Proton therapy has the potential for homogeneous irradiation of the target volume while reducing the magnitude and/or extent of the low dose area outside the target volume. This may be clinically relevant for long-term effects in children. Proton radiotherapy has an established role in the treatment of children with chordomas and chondrosarcomas of the base of skull. Planning studies have demonstrated the potential for improving the therapeutic ratio for radiotherapy for tumours of the central nervous system by achieving a uniform dose within the target volume while minimizing the severity of neuropsychological sequelae. Clinical experience of proton radiotherapy for children remains limited with potential areas for clinical research.

Biomedical Research↗
PubMed2002

DRD4 promoter SNPs and gender effects on Extraversion in African Americans.

There is strong evidence for genetic influences on personality traits. Interest in one such gene, the dopamine D4 receptor (DRD4) grew after an exon III polymorphism was associated with Novelty Seeking and related measures of Extraversion. However, the findings were not confirmed in later studies. Recently, a -521C/T single nucleotide polymorphism (SNP) within the promoter region of the DRD4 gene was found to be related to Novelty Seeking scores in populations from Japan and Hungary. Since little is known about the role DRD4 plays in personality in other populations we evaluated if two DRD4 promoter SNPs, -521C/T and -616C/G, were related to personality traits in African Americans. Personality traits were measured by the NEO-FFI in 71 unrelated African Americans. Genotyping was performed using PCR-RFLP. Multivariate analyses of variance (MANOVA) were performed to evaluate the effects of gender and -616 and -521 genotypes on personality traits. A significant three-way interaction effect from gender, -616 genotype, and -521 genotype was observed for Extraversion scores (F(1,54) 5.86, P < 0.02). Subsequent analyses revealed that the association was mainly due to -521C/T genotype among females (P = 0.01). This study provides further evidence that genetic variation within the DRD4 promoter and gender differences contribute to variation in Novelty Seeking behaviors such as Extraversion.

Adult↗
PubMed2001

Involvement of non-NMDA receptors in the rescue of weaver cerebellar granule neurons and sensitivity to ethanol of cerebellar AMPA receptors in oocytes.

The cellular mechanism responsible for the death of cerebellar granule neurons in the weaver mutant mouse is still being intensely investigated. To determine if alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors are involved in producing the weaver phenotype or are altered by the weaver gene, we used (1) reverse transcription and polymerase chain reaction (RT-PCR) to detect transcripts of glutamate receptors (GluR1-4) from wild-type and mutant cerebella; (2) immunocytochemistry to establish the types of glutamate receptors present in granule neurons cultured from normal and homozygous weaver postnatal day 5-6 (P5-6) cerebella; (3) 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a blocker of glutamate (AMPA/Kainate/NMDA) receptors, and 6,7-dinitroquinoxaline-2,3-dione (NBQX), a blocker of AMPA and kainate receptors, to assess the number of neurons and the number of neurons with long neurites in cultures of homozygous weaver granule neurons; (4) two-electrode voltage clamp recordings to study AMPA glutamate receptor expression in Xenopus oocytes after injection of mRNA isolated from cerebella of normal and weaver P5-6, postnatal day 10 (P10) and postnatal day 23 (P23) mice; and (5) ethanol, which at low 1-10 mM concentrations had been shown previously to rescue homozygous weaver granule neurons in culture [Liesi et al., J. Neurosci. Res. 48 (1997) 571-579], to examine its effect on modulation of AMPA receptors expressed from mRNA. By RT-PCR, the mRNA coding for AMPA receptor subunits GluR1-4 were detected from +/+ and wv/wv cerebella, and by immunocytochemistry, GluR1, GluR2/3 and GluR4 were observed to be expressed in cultured +/+ and wv/wv granule cells. CNQX at 10 microM or NBQX at 10 microM significantly increased the number of surviving neurons and the number with long neurites as compared to wv/wv controls. In addition, CNQX was significantly more effective than NBQX. In oocytes injected with mRNA from P10 normal or weaver cerebella, the amplitudes of the responses to kainate were about equal. In contrast, the amplitudes of the kainate-activated currents in oocytes injected with weaver P23 mRNA were about twice as large as the currents observed in oocytes injected with mRNA from normal P23 cerebella, and both were larger than kainate-activated currents observed after injection of P10 normal and weaver mRNA. Kainate-activated AMPA receptor currents in oocytes injected with mRNA from P10 and P23 normal and homozygous weaver cerebella were inhibited by ethanol. There were no significant differences in the inhibition produced by ethanol on currents from P10 or P23 normal and wv/wv mRNA. Thus, P23 weaver cerebellar mRNA expressed more kainate-activated current in oocytes than P23 normal cerebellar mRNA; both normal and weaver cerebellar granule neurons express mRNA coding for functional AMPA receptors that are susceptible to ethanol inhibition.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2001

Total synthesis of epothilones B and D.

[reaction: see text] A highly convergent total synthesis of the natural products epothilone B and D is described. The route is highlighted by efficient generation of a C12-C13 trisubstituted olefin which exploits a sequential Nozaki-Hiyama-Kishi coupling and a stereoselective thionyl chloride rearrangement.

Alkenes↗
PubMed2001

Kinetically controlled cross-metathesis reactions with high E-olefin selectivities.

[reaction: see text] Homoallylic alcohols with anti-allylic substituents display enhanced E-olefin selectivity in cross-metathesis (CM) reactions with allyltrimethylsilane. The high selectivity can be explained via a five-membered chelate intermediate in which the hydroxyl group of the homoallylic alcohol coordinates to the ruthenium metal center of Grubbs' catalyst.

Journal Article↗
PubMed2001

A PDE6A promoter fragment directs transcription predominantly in the photoreceptor.

Rod photoreceptor cGMP phosphodiesterase (PDE6) is a key enzyme in the phototransduction cascade. Lines of transgenic mice were established to determine the spatial expression pattern directed by an upstream fragment of the PDE6A gene. RT-PCR analysis showed that three of four lines analyzed transcribed the transgene predominantly in the retina and weakly in brain. The line showing no transgene transcription did not contain an intact transgene. Transcription of the transgene in the three lines was found in retina and weakly in brain, but not in heart, kidney, liver, or lung. Transcripts were most predominant in the photoreceptors of the retina. These results demonstrate that a short segment of the upstream region of the PDE6A gene comprises a functional promoter that is most active in photoreceptors.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Reproducible high efficiency gene transfer into Y79 retinoblastoma cells using adenofection.

Several photoreceptor-specific genes are actively transcribed in Y79 retinoblastoma (Rb) cells, making this cell line potentially useful for the study of photoreceptor metabolism. The utility of these cells is limited because commonly used methods of gene transfer into Y79 cells are inefficient and lack reproducibility. In contrast, we found that adenovirus transduction yields high efficiency gene transfer, however, generation of recombinant adenovirus is lengthy and time consuming. Here, we show that adenofection, a method of coupling adenovirus to plasmid DNA for improved gene transfer, is efficient for gene delivery into Y79 cells. Recombinant adenovirus expressing bacterial lacZ was noncovalently complexed to GFP or luciferase reporter plasmids with polyethylenimine. Efficiency of plasmid gene delivery was determined by monitoring GFP fluorescence. For comparison, calcium phosphate-mediated or cationic lipid transfection was performed in Y79 and HEK293 cells using standard protocols. The adenofection protocol yielded significantly higher efficiencies in Y79 cells than that obtained in these cells with calcium phosphate or cationic lipids. This method will facilitate any experiment requiring reproducible high-level gene transfer. Here, we show that adenofection can be used to analyze activity of the rod photoreceptor PDE6A gene promoter.

Adenoviridae↗
PubMed2001

Human plasma carboxylesterase and butyrylcholinesterase enzyme activity: correlations with SN-38 pharmacokinetics during a prolonged infusion of irinotecan.

PURPOSE: To characterize the relationships between human plasma irinotecan carboxylesterase-converting enzyme activity, caboxylesterase-mediated hydrolysis of p-nitrophenyl acetate (pNPA), and the butyrylcholinesterase-mediated hydrolysis of butyrylthiocholine in human plasma and to test the ability of these in vitro tests to predict the variability in SN-38 pharmacokinetics in adult patients during a prolonged infusion of irinotecan. METHODS: Individual plasma-converting enzyme activity was measured in 20 adult cancer patients participating in a pharmacokinetic and phase I clinical trial of a prolonged 96-h intravenous infusion of irinotecan. The pNPA and butyrylthiocholine hydrolysis in patient plasma was also assayed. RESULTS: The irinotecan carboxylesterase-converting enzyme in human plasma had a Vmax of 89.9 +/- 22.7 pmol/h per ml plasma and a Km of 207 +/- 56 microM (mean +/- SD, n = 3). The mean value of the specific activity of this enzyme in 20 adult cancer patients was 10.08 +/- 2.96 pmol/h per ml plasma ranging from 5.43 to 15.39 pmol/h per ml. The area-under-the-concentration-versus time curve (AUC) ratio of SN-38 to irinotecan (AUCSN-38/AUCCPT-11) was used to assess the relative SN-38 exposure to the active metabolite in individual patients. Pharmacokinetic variations in the relative exposure to SN-38 did not correlate with the measured carboxylesterase-converting enzyme activity nor with plasma butyrylcholinesterase activity in our patient population. However, it did correlate with the measured pNPA hydrolysis activity in patient plasma (r2 = 0.350, P = 0.0124, n = 18). CONCLUSIONS: Determination of patient plasma pNPA hydrolysis activity may have utility in predicting SN-38 pharmacokinetics during prolonged infusions of irinotecan.

Antineoplastic Agents, Phytogenic↗
PubMed2001

United Kingdom Children's Cancer Study Group (UKCCSG) radiotherapy and brain tumour groups: medulloblastoma/PNET and craniospinal radiotherapy (CSRT): report of a workshop held in Leeds, 30 June 1999.

Primitive neuroectodermal tumours (PNET), of which cerebellar medulloblastoma is the most frequent, are embryonal central nervous system tumours arising mainly in children. They are characterized by their propensity for metastasis via the cerebrospinal fluid. They are radiosensitive and craniospinal radiotherapy (CSRT) is an important part of their management. This is a complex radiotherapy (RT) technique, the accuracy of which contributes to the survival and quality of survival of treated children. In the last 25 years, European and North American collaborative studies have investigated the role of adjuvant chemotherapy. The planning and delivery of CSRT have to be of the highest quality. It is important to incorporate all modern technical RT developments into CSRT. It is possible that optimizing fractionation may further improve outcome. The purpose of this workshop was to review the current status of CSRT planning and administration in the light of RT developments. Current results of the treatement of medulloblastoma and PNET were reviewed and UK involvement in possible future collaborative trials was discussed.

Brain↗
PubMed2001

Death of neurasthenia and its psychological reincarnation: a study of neurasthenia at the National Hospital for the Relief and Cure of the Paralysed and Epileptic, Queen Square, London, 1870-1932.

BACKGROUND: The diagnosis of neurasthenia appeared in 1869 and rapidly became fashionable and highly prevalent. It disappeared almost completely, producing ongoing debates about what happened to the disease, which have not so far been informed by empirical data. AIMS: To use empirical historical hospital data from one specific hospital to explore several controversies about neurasthenia, including what happened to the disorder. METHOD: The annual reports of Queen Square Hospital were examined from 1870 to 1947. The prevalence of neurasthenia diagnoses as a proportion of total discharges was recorded. The possible diagnostic categories into which neurasthenia could have been reclassified were identified. Textbooks and writing by neurologists working at the hospital during this period were examined. RESULTS: Neurasthenia accounted for 6-11% of total discharges from the late 1890s to 1930, when it virtually disappeared. Men accounted for 33-50% of cases. CONCLUSIONS: Neurasthenia affected both the upper and working classes and both men and women. Neurologists, not psychiatrists, continued to see the disorder well into the 20th century. Neurasthenia did not disappear, but was reclassified into psychological diagnoses.

History, 19th Century↗
PubMed2000

Attachment style in patients with unexplained physical complaints.

BACKGROUND: Patients who present with physical symptoms that lack an organic explanation are common, difficult to help and poorly understood. Their medical help-seeking is a form of care-eliciting behaviour and, as such, may be understandable in terms of attachment style. Adult attachment style influences functioning in relationships, and may affect help-seeking behaviour from professional carers such as the family doctor. METHOD: A consecutive sample of 2,042 primary-care attenders completed questionnaires on: the reason for consultation, attribution of symptoms, psychiatric distress (GHQ), somatic distress (BSI), and self-reported adult attachment style (ASQ). Their doctors rated presentations into explained physical, unexplained physical, or psychological. RESULTS: There is a powerful relationship between type of presentation and adult attachment style. Both abnormal attachment and level of psychiatric distress increased significantly from the explained physical group, through the unexplained physical group to the group who presented psychologically. Logistic regression models determined three explanatory variables that made significant independent contributions to presentation type: psychiatric distress, attachment style and symptom attribution. CONCLUSION: Presentation to the doctor with unexplained physical symptoms is associated with both higher levels of psychiatric symptoms and abnormal attachment style when compared to presentations with organic physical symptoms. Patients who present overt psychological symptoms suffer more psychiatric distress and have more abnormal attachment than those presenting physical symptoms (either organically explained or unexplained). Models to explain these findings are discussed.

Adolescent↗