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Biomedical subjects

E Thompson

Publications and source records attributed to E Thompson.

At least 109 records · Page 6Linked to original sources

Evaluation of the effectiveness of guidelines, audit and feedback: improving the use of intravenous thrombolysis in patients with suspected acute myocardial infarction.

OBJECTIVE: To determine the effectiveness of medical audit as a means of improving the use of intravenous thrombolytics in patients with suspected acute myocardial infarction. DESIGN: Time-series analyses of observations in four study hospitals conducting repeated audits and feedback compared to a control hospital. SETTING: Five district general hospitals in North West Thames Region between April 1991 and July 1992. SUBJECTS: 2593 patients admitted as emergencies with a suspected acute myocardial infarction. MAIN OUTCOME MEASURES: Proportion of eligible cases receiving intravenous thrombolytic therapy observed in each audit and proportion of patients in whom this therapy was used appropriately. RESULTS: In the baseline audits, the proportions of eligible cases receiving thrombolytic therapy in the four study hospitals were 94%, 60%, 58% and 57%, and 53% in the control hospital. After three further audits in each study hospital over the subsequent year, the observed proportions had changed to 88% (to 6%), 92% (+32%), 95% (+37%), and 7796 (+20%). Meanwhile the proportion in the control hospital rose to 68% (+15%). The trend over time was significant in the second and third hospitals but not in the other two study hospitals or the control hospital. Reclassification of those cases in which the reliability of the diagnosis was poor altered the extent but not the direction of observed trends. Generally, the appropriateness of use of thrombolytic therapy increased with increasing treatment rates. There was a suggestion, however, that continued auditing in the presence of high treatment rates may have led to a reduction in appropriateness. CONCLUSIONS: medical audit can be an effective means of improving the use of intravenous thrombolytics. It is possible that over auditing may result in greater inappropriate use.

Algorithms↗

Positron emission tomography in the detection and management of metastatic melanoma.

Initial reports suggest that positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) may offer greater diagnostic accuracy and versatility than conventional radiology in staging patients with metastatic melanoma. We reviewed the first 100 melanoma patients to have PET imaging at our institution. PET findings were correlated with all other available results, including plain X-ray, computed tomography (CT), magnetic resonance (MR) imaging, bone scintigraphy, clinical findings and histopathology. A total of 415 metastatic lesions were evaluated, 388 (93%) of which were detected by PET. In 20 patients, PET detected 24 metastases up to 6 months earlier than conventional imaging or physical examination. Selection of surgical or medical management was specifically influenced by PET findings in 22 patients, and PET was used to clarify another 12 cases where CT was inconclusive. In nine patients undergoing chemotherapy, PET was used to assess response to treatment. We conclude that FDG-PET can accurately detect metastatic melanoma with a single non-invasive scan, and can demonstrate some metastases months before conventional imaging techniques. PET can improve the selection of patients for surgery, has potential for monitoring response to treatment and may prove a cost-effective means of staging melanoma patients.

Adult↗

Educating psychiatric patients about their treatment: do fact sheets work?

Psychiatric patients are sometimes given fact sheets about their treatment but the benefits of these are uncertain. We tested three strategies in three cohorts of psychiatric inpatients--fact sheets alone, fact sheets and subsequent discussion, and control. Knowledge of medication was assessed by questionnaire. For various reasons, only 33 of the 77 patients were included in the study or analysis. Of the patients who had been given fact sheets, 87% independently read them and reported finding them helpful whilst all asked for more information. Receiving a fact sheet alone had no significant effect, whereas having discussed it with a health care professional was associated with a significant increase in knowledge about medication. Patients receiving fact sheets selectively learned more about side-effects than about drug action or precautions. This strategy for patient education could be used by ward nurses and deserves further evaluation.

Adolescent↗

Gene mutations in 21 unrelated cases of phenotypic heterozygous protein C deficiency and thrombosis. Protein C Study Group.

Mutations have been identified in the protein C gene in 21 patients with venous thromboembolism and phenotypic heterozygous protein C deficiency. In 20 probands, single mutations were the only abnormalities identified by sequencing all coding regions, intron exon boundaries and the promoter region back to -1540. In one proband 2 mutations were identified and in another family 2 mutations were identified (but not both in the proband). Of the 23 mutations, 18 resulted in predicted amino acid substitutions, 3 were mutations resulting in stop codons, one was a mutation within a consensus splice sequence and another a 9 base pair insertion within exon 5 (this region within exon 5 is proposed as a deletion/insertion hot spot). A novel polymorphism was also, uniquely, identified in the propeptide region of the molecule (Pro-21Pro; CCT to CCC) in a kindred from Hong Kong. Cosegregation of the protein C gene mutation with protein C deficiency could be determined in 13 families. In a further family, phenotypic protein C deficiency and the genetic mutation cosegregated in only 4/5 members. The first thrombotic incident occurred in the probands between the ages of 11 and 59 years and 12 individuals suffered recurrent thrombosis. Thrombosis occurred in at least one other family member in 9/21 families, but in 2 of these it was inconsistently associated with protein C deficiency. An independent genetic risk factor, factor V Arg506Gln (FV Leiden) was identified in 2 probands (and 3 family members) and in 4 protein C deficient members of a third family but not in the proband. The results suggest that in the majority of probands with thrombosis and phenotypic protein C deficiency, a single protein C gene mutation is associated with thrombosis. However, it is also possible that additional unknown genetic risk factors contribute to the thrombotic risk. An added, acquired, risk factor leads to thrombosis at an early age (< 25 years).

Adolescent↗

Evidence for the late origin of introns in chloroplast genes from an evolutionary analysis of the genus Euglena.

The origin of present day introns is a subject of spirited debate. Any intron evolution theory must account for not only nuclear spliceosomal introns but also their antecedents. The evolution of group II introns is fundamental to this debate, since group II introns are the proposed progenitors of nuclear spliceosomal introns and are found in ancient genes from modern organisms. We have studied the evolution of chloroplast introns and twintrons (introns within introns) in the genus Euglena. Our hypothesis is that Euglena chloroplast introns arose late in the evolution of this lineage and that twintrons were formed by the insertion of one or more introns into existing introns. In the present study we find that 22 out of 26 introns surveyed in six different photosynthesis-related genes from the plastid DNA of Euglena gracilis are not present in one or more basally branching Euglena spp. These results are supportive of a late origin for Euglena chloroplast group II introns. The psbT gene in Euglena viridis, a basally branching Euglena species, contains a single intron in the identical position to a psbT twintron from E.gracilis, a derived species. The E.viridis intron, when compared with 99 other Euglena group II introns, is most similar to the external intron of the E.gracilis psbT twintron. Based on these data, the addition of introns to the ancestral psbT intron in the common ancester of E.viridis and E.gracilis gave rise to the psbT twintron in E.gracilis.

Animals↗

Generation and molecular cytogenetic characterization of a radiation-reduction hybrid panel for human chromosome 6.

A neoR marked chromosome-6 containing hybrid (D113JA) was used to generate a panel of 15 radiation-reduced hybrid cell lines. The panel was constructed by irradiating microcells isolated from D113JA at 800 or 8000 rads, providing different levels of chromosome 6 retention. These hybrids have been systematically analyzed using interspersed repetitive elements, previously assigned markers for chromosome 6, and fluorescent in situ hybridization (FISH). As expected, G418 selection has favored the retention of fragments near the insertion site of the neoR gene (6q16). The panel as constituted provides an important resource for regional assignment of molecular markers, especially to regions on 6q.

Animals↗

RAS and FMS mutations following cytotoxic therapy for childhood acute lymphoblastic leukaemia.

Patients who have received cytotoxic therapy for primary neoplastic disease are at an increased risk of developing secondary (therapy-related) acute myeloid leukaemia (AML) or myelodysplasia (MDS). RAS and FMS mutations have been observed in patients with AML and MDS. It has been suggested that the mutational status within these genes may be predictive of early secondary leukaemic disease. In this study we have screened 50 haematologically normal patients in complete remission from childhood acute lymphoblastic leukaemia (ALL) for activating point mutations in the RAS and FMS proto-oncogenes. Such patients may be considered at risk of therapy-related disease. Codons 12, 13 and 61 were screened in RAS and codon 969 in FMS using the polymerase chain reaction (PCR) followed by oligonucleotide hybridization (ONH). Three of the 50 patients (6%) were found to harbour N12 RAS mutations. One of these three patients (2%) had both a N12 RAS and FMS 969 mutation. Upon sequencing the RAS mutations, substitutions of serine, cysteine and aspartic acid for glycine were identified. The FMS 969 mutation was also confirmed, by sequencing, as a histidine substitution. RAS mutations were not detected in presentation samples indicating that these lesions have been somatically acquired presumably subsequent to cytotoxic therapy for the primary disease. Continued follow-up of these patients may indicate a role for these mutations in the development of secondary malignancies.

Antineoplastic Combined Chemotherapy Protocols↗

Mammalian cell gene mutation assays working group report.

As part of the International Workshop on Standardization of Genotoxicity Test Procedures, in Melbourne, 27-28 February 1993, various international guidelines were examined with respect to protocol issues in the area of mammalian cell gene mutation assays. The working group on mammalian cell gene mutation assays discussed a wide range of protocol issues related to study design; in most cases the recommendations are reasonably consistent with existing guidelines. Agreement was reached on several issues as follows. The upper limit of concentration for testing non-toxic substances should be 10 mM or 5 mg/ml, whichever is lower. For testing toxic substances the criteria of an acceptable upper limit of concentration should yield 10-20% survival. Any of several established mammalian cell mutation assays (L5178Y TK+/-, CHO/HPRT, AS52/XPRT, V79/HPRT) can be used to evaluate mutagenesis in mammalian cells; the ouabain (Na/K-ATPase) system is not an acceptable mutation assay for routine evaluation of mutagenesis in mammalian cells. Ability to recover small colonies must be convincingly demonstrated when using the L5178Y TK+/- mouse lymphoma assay. In the mouse lymphoma assay (L5178Y TK+/-), colonies in positive controls and at least two (if available) representative positive doses of the test compound should be sized if a positive response is seen; in the event of a negative response due to the test compound, colony sizing of the positive control is necessary to validate the conduct of the assay. Testing both in the presence and absence of S9 metabolic activation is necessary. It was not possible to come to a firm conclusion about the length of treatment. There was a general agreement that extended treatment times (> 2 cell cycles) often bear more disadvantages than advantages and should only be used with adequate justification. It is not necessary to repeat clear positive or clear negative tests when the assay has been adequately performed; this recommendation differs significantly from the UK guidelines. If treatment groups are not replicated, the numbers of doses tested should be increased; this recommendation differs significantly from the UK guidelines. Each laboratory should establish a historical database for the performance of a given assay in that laboratory.

Animals↗

An algorithm for Monte Carlo estimation of genotype probabilities on complex pedigrees.

Exact probability and likelihood computation on complex pedigrees is often infeasible, since exact methods are too computationally intensive even with today's computing technology. A statistical tool, Markov chain Monte Carlo (MCMC), is increasingly being explored as a technique for estimating probabilities of genotypic configurations on pedigrees conditional on phenotypic data. However, this conditional probability distribution on a complex pedigree is, in general, multimodal, and multimodality is one of the major difficulties in MCMC exploration of a probability surface. In this paper, a new member of the MCMC Metropolis-Hastings class of algorithms is proposed; the heated-Metropolis algorithm. The algorithm achieves passage through low probability states to other local modes of the probability distribution, and so provides much improved estimates of probabilities of interest. The example considered is the estimation of the probabilities of carrier genotype for the founders of a complex pedigree in which a very rare lethal recessive trait is segregating.

Algorithms↗

Symptoms and health status before and six weeks after open cholecystectomy: a European cohort study.ECHSS Group. European Collaborative Health Services Study Group.

The impact of open cholecystectomy on patients' symptoms and health status and their level of satisfaction has been examined to provide a basis for comparison with newer rival treatments. A prospective cohort study using patient and surgeon completed questionnaires before and six weeks after surgery was carried out in 14 general hospitals in eight European countries. Five hundred and eighty three patients were recruited consecutively in 1990 to 1991. Information on their symptoms, general health status, activities of daily living, and satisfaction with their care were collected. After surgery 42.8% of patients reported that they were free of symptoms. Symptoms varied in their responsiveness to surgery--six weeks after surgery 89% of those who had complained of vomiting had improved, 81% of nausea, 69% of loss of appetite, 65% of abdominal pain, and 51% of flatulence. In contrast 28.1% of patients still suffered from flatulence and 23.5% continued to complain of abdominal pain. Most patients' (62.7%) general health improved, 28% were unchanged, and 9.3% were worse. After surgery most patients reported no restrictions in their normal social activities (75-90% depending on the activity) and most (89.5%) felt the results of their operation had been as expected or better than expected. Most patients undergoing open cholecystectomy reported an improvement in their symptoms, health status, and social functioning. This was reflected in their high level of satisfaction. Some patients, however, gained no benefit and a small proportion were worse than before surgery.

Activities of Daily Living↗

Pharmacokinetic properties of methadone hydrochloride after single intramuscular administration in adult dairy goats.

Pharmacokinetic parameters of methadone were studied in adult dairy goats. Five goats were each given methadone hydrochloride as a single 0.2 mg/kg of body weight dosage by intramuscular (IM) administration. Plasma methadone concentrations were determined for 96 h after dosing. Plasma methadone concentrations after IM administration were best described by an open one-compartment model. Overall elimination half-life (t1/2) was 1.38 h. Peak plasma concentrations were reached 0.25 h after dosing, and the actual plasma concentration averaged 37.8 ng/ml (SD = 12.76) at that time. The data obtained from this study suggest that plasma concentrations, similar to those that are analgesic in humans, can be achieved after IM administration of methadone at a dose rate of 0.2 mg/kg of body weight. In addition, these plasma concentrations can be maintained for up to 3 h after a single injection and, therefore, may provide satisfactory analgesia for such period.

Animals↗

A clinical follow-up of British patients with FG syndrome.

The FG syndrome is an X-linked recessive mental retardation syndrome. Ten patients are reviewed with special emphasis on the natural history of the intellectual development, constipation, and the prognosis for growth and behaviour. Six out of 10 patients are still macrocephalic, and there is no evidence for a specific growth pattern with respect to height. The degree of mental retardation is is usually severe. The behaviour is characteristically friendly, sociable and over-talkative, with periodic aggression. Six patients have seizures. A characteristic progression seems to occur from congenital hypotonia with joint hyperlaxity at birth, to joint contractures with apparent spasticity and unsteady gait later in life. The constipation was a temporary problem in five cases. The cowlick and the fetal pads persist and are important, but not specific, for the diagnosis.

Abnormalities, Multiple↗

Finding noncommunicating sets for Markov chain Monte Carlo estimations on pedigrees.

Markov chain Monte Carlo (MCMC) has recently gained use as a method of estimating required probability and likelihood functions in pedigree analysis, when exact computation is impractical. However, when a multiallelic locus is involved, irreducibility of the constructed Markov chain, an essential requirement of the MCMC method, may fail. Solutions proposed by several researchers, which do not identify all the noncommunicating sets of genotypic configurations, are inefficient with highly polymorphic loci. This is a particularly serious problem in linkage analysis, because highly polymorphic markers are much more informative and thus are preferred. In the present paper, we describe an algorithm that finds all the noncommunicating classes of genotypic configurations on any pedigree. This leads to a more efficient method of defining an irreducible Markov chain. Examples, including a pedigree from a genetic study of familial Alzheimer disease, are used to illustrate how the algorithm works and how penetrances are modified for specific individuals to ensure irreducibility.

Algorithms↗

Personal services.

Dutch experience seems to show that a liberal societal attitude to sex and sexuality encourages young people to be more confident in asking for the contraceptive services they need, writes Elinor Thompson.

Adolescent↗