Biomedical subjects
E Thompson
Publications and source records attributed to E Thompson.
Influence of demographic variables on neuropsychological test performance after traumatic brain injury.
The validity of correcting for demographic variables when considering neuropsychological test scores was evaluated in a sample of 136 patients with traumatic brain injury (TBI) who had been screened carefully for premorbid or comorbid confounding factors. When considered in concert with neurological variables, age and education accounted for a significant proportion of the variance in raw scores on the Category Test and the Trail Making Test in the complete sample. Gender did not affect level of test performance. Correcting neuropsychological test scores for demographic variables did not significantly alter their success in identifying patients with severe TBI, but did lead to greater accuracy when classifying individuals with mild-moderate TBI. This investigation concluded that norms that consider the demographic background of the individual are likely to reflect more accurately the neuropsychological status of patients with TBI than interpretations that are based exclusively on raw data.
Cidofovir protects mice against lethal aerosol or intranasal cowpox virus challenge.
The efficacy of cidofovir for treatment of cowpox virus infection in BALB/c mice was investigated in an effort to evaluate new therapies for virulent orthopoxvirus infections of the respiratory tract in a small animal model. Exposure to 2(-5)x10(6) pfu of cowpox virus by aerosol or intranasally (inl) was lethal in 3- to 7-week-old animals. One inoculation of 100 mg/kg cidofovir on day 0, 2, or 4, with respect to aerosol infection, resulted in 90%-100% survival. Treatment on day 0 reduced peak pulmonary virus titers 10- to 100-fold, reduced the severity of viral pneumonitis, and prevented pulmonary hemorrhage. The same dose on day -6 to 2 protected 80%-100% of inl infected mice, whereas 1 inoculation on day -16 to -8 or day 3 to 6 was partially protective. Cidofovir delayed but did not prevent the death of inl infected mice with severe combined immunodeficiency. Treatment at the time of tail scarification with vaccinia virus did not block vaccination efficacy.
Cardiovascular stress associated with concentric and eccentric isokinetic exercise in young and older adults.
Heart rate (HR), mean arterial blood pressure (MAP), and rate-pressure product (RPP) responses to submaximal isokinetic concentric (CON) and eccentric (ECC) knee extension exercise were compared at the same absolute torque output in 20 young (mean+/-SD=23.2+/-1.7 years) and 20 older (mean+/-SD=75.2+/-4.6 years) adults. After determination of peak CON and ECC torques, subjects performed separate, randomly ordered, 2-minute bouts of isokinetic CON and ECC exercise (90 degrees/s, exercise intensity: 50% of CON peak torque). CON exercise elicited greater changes in HR, MAP, and RPP than ECC exercise (p<.001) for both age groups. There were no age-related differences in HR, MAP, or RPP responses for either CON or ECC exercise. At the same absolute torque output, isokinetic CON knee extension exercise elicited significantly greater increases in cardiovascular stress than ECC exercise in both young and older adults. This result has implications for determining appropriate fitness and rehabilitation programs.
A cost effectiveness analysis of goserelin compared with danazol as endometrial thinning agents.
OBJECTIVE: To analyse the cost, effectiveness and cost effectiveness of two endometrial thinning agents prior to laser ablation for dysfunctional uterine bleeding: danazol and goserelin. SETTING: A district general hospital. DESIGN: A retrospective cost effectiveness analysis, from the perspective of the health service, based on data from an open, randomised, parallel group comparative study of 160 pre-menopausal women with dysfunctional uterine bleeding. METHODS: Within the trial, length of operation and duration of hospital stay was recorded for each woman. Resource use due to complications of surgery and adverse drug events was evaluated by one of the authors (R.G.). Additional surgery after completion of the study was collected using a postal questionnaire which was distributed to every woman who had undergone surgery. Resource use was costed using detailed unit costs from a specific NHS trust and from published sources. A cost effectiveness analysis was undertaken relating differential cost to differential rates of amenorrhoea at women's last point of follow up. RESULTS: Information on amenorrhoea was available from 138 women, of whom 111 had completed the questionnaire to indicate longer term follow up. Women who did not complete the clinical trial were not included in this economic evaluation. On average, women randomised to goserelin spent less time in theatre and on the ward. Based on longer term follow up, rates of retreatment were similar in the two groups. The mean (SD) health service cost of women in the goserelin group was pound sterling 323.84 (pound sterling 309.94), compared with pound sterling 243.45 (pound sterling 265.23) in the danazol group; median (range) costs were pound sterling 220.29 (pound sterling 191-pound sterling 2127) and pound sterling 159.76 (pound sterling 140-pound sterling 1426) in the two groups, respectively. These costs were significantly higher for goserelin (P = 0.0001). The goserelin group also had a higher rate of amenorrhoea (38.8% vs 28.6%, P = 0.23). Based on mean differences in cost, the incremental cost of goserelin per additional woman with amenorrhoea was pound sterling 788; based on median differences in cost the ratio was pound sterling 590. CONCLUSIONS: The shorter duration in theatre and stay in hospital provided a modest offset of the higher acquisition cost of goserelin, but the overall cost of management remained significantly higher than managing women with danazol. The rates of amenorrhoea indicated that goserelin was more effective at 24 weeks and approximately two years after surgery, although statistical significance was only achieved at 24 weeks. The economic impact of women withdrawn from treatment was not considered, but sensitivity analysis indicates that these women may have had a large effect on the overall result of this study. Purchasers will need to decide whether the additional cost of management with goserelin is justified by the increased rates of amenorrhoea and the reduced withdrawals from treatment.
Attitudes to genetic testing for breast cancer susceptibility in women at increased risk developing hereditary breast cancer.
Explore the source record for details and available documents.
Methylenetetrahydrofolate reductase 677 C-->T mutation and coronary heart disease risk in UK Indian Asians.
Plasma homocysteine concentrations are elevated in UK Indian Asians and may contribute to twice as many coronary heart disease (CHD) deaths in this group compared with European whites. The mechanisms underlying elevated homocysteine concentrations among Indian Asians are not well understood. In this study, we have investigated the extent to which the methylenetetrahydrofolate reductase (MTHFR) 677 C-->T mutation accounts for elevated plasma homocysteine and increased CHD risk in Indian Asians compared with European whites. We investigated 454 male cases (with myocardial infarction or angiographically proven CHD: 224 Indian Asians, 230 European whites) and 805 healthy male controls (381 Indian Asians, 424 European whites). Fasting homocysteine concentrations, MTHFR 677 C-->T genotype, and conventional CHD risk factors were measured. The prevalence of homozygous MTHFR 677T in Indian Asian controls was less than one third that in European white controls (3.1% versus 9. 7%, P<0.001). In Indian Asians, the TT MTHFR genotype was not associated with homocysteine concentrations and was not present in any of the Asian controls with hyperhomocysteinemia (>15 micromol/L). In contrast, among European whites, the TT MTHFR genotype was strongly related to elevated plasma homocysteine concentrations and was found in 27% of the European controls with hyperhomocysteinemia. Elevated homocysteine in Indian Asian compared with European white controls was accounted for by their reduced levels of B vitamins but not by the MTHFR 677T genotype. However, neither the TT MTHFR genotype nor B vitamin levels explained the elevated homocysteine concentrations in CHD cases compared with controls. TT MTHFR was not a risk factor for early-onset CHD in Indian Asians (odds ratio, 0.5; 95% confidence interval, 0.1 to 2.4; P=0.39), unlike in European whites (odds ratio, 2.1; 95% confidence interval, 1.1 to 4. 1; P=0.02). We conclude that the MTHFR 677T: mutation does not contribute to elevated plasma homocysteine concentrations or increased CHD risk in Indian Asians compared with European whites. Our results suggest that novel genetic defects and/or environmental factors influence homocysteine metabolism in Indian Asians residing in the United Kingdom.
Assessment of incomplete effort with the California Verbal Learning Test.
The false-positive rates of 2 formulas for the detection of incomplete effort on the California Verbal Learning Test (CVLT; Delis, Kramer, Kaplan, & Ober, 1987) were evaluated in a sample of 134 patients with traumatic head injury (THI) who had been carefully screened to eliminate any individuals who might be expected to have financial incentives for poor performance. One formula incorrectly identified only 7.46% of the sample as providing incomplete effort, confirming its potential usefulness in clinical settings. The other formula fared much worse, misidentifying an unacceptably high 18.66% of the sample. Lower levels of education were found to increase the likelihood of false-positive results with that formula. It is concluded that the CVLT holds promise for the evaluation of incomplete effort after THI but only within the context of a more comprehensive neuropsychological evaluation.
A pilot scheme for the development of evidence-based practice.
This article presents an evaluative account of a pilot scheme that aimed to introduce evidence-based practice in one NHS trust. The scheme was based on collaboration between staff in the quality assurance department and a nurse researcher based in a university. This collaboration enabled three designated staff to develop skills required for evidence-based practice and guide the production of information that could be disseminated to nurses throughout the trust. Evaluation demonstrated that participants had examined eight practice-based topics and devised protocols that could be applied to practice in a range of hospital and community settings throughout the trust. Evaluation also highlighted the importance of ensuring that members of other disciplines are aware of, and feel involved in, new developments even if they are not directly concerned with them.
Familial overexpression of beta antithrombin caused by an Asn135Thr substitution.
We have investigated the basis of antithrombin deficiency in an asymptomatic individual (and family) with borderline levels (approximately 70% antigen and activity) of antithrombin. Direct sequencing of amplified DNA showed a mutation in codon 135, AAC to ACC, predicting a heterozygous Asn135Thr substitution. This substitution alters the predicted consensus sequence for glycosylation, Asn-X-Ser, adjacent to the heparin interaction site of antithrombin. The antithrombin isolated from plasma of the proband by heparin-Sepharose chromatography contained amounts of beta antithrombin (the very high affinity fraction) greatly increased (approximately 20% to 30% of total) above the trace levels found in normals. Expression of the residue 135 variant in both a cell-free system and COS-7 cells confirmed altered glycosylation arising as a consequence of the mutation. Wild-type and variant protein were translated and exported from COS-7 cells with apparently equal efficiency, in contrast to the reduced level of variant observed in plasma of the affected individual. This case represents a novel cause of antithrombin deficiency, removal of glycosylation concensus sequence, and highlights the potentially important role of beta antithrombin in regulating coagulation.
Identification of randomized controlled trials from the emergency medicine literature: comparison of hand searching versus MEDLINE searching.
STUDY OBJECTIVE: As part of an ongoing project to identify all the randomized controlled trials (RCTs) in the emergency medicine literature, in association with the Cochrane Collaboration, 2 discrete studies were undertaken; the first, to compare motives for active participation in hand searching of the literature by emergency medicine professionals, and the second, to compare hand searching with MEDLINE searching of a number of emergency medicine journals. METHODS: All listed members of the British Association for Emergency Medicine (BAEM) and the Society for Academic Emergency Medicine (SAEM) received a standard letter outlining the objectives of the project, with 1 of 3 headings assigned on an alternate basis. Recruited volunteers hand searched journals prioritized from the emergency medicine literature. Each issue of each journal was hand searched for RCTs. In addition, a comprehensive MEDLINE search was conducted for each journal. The yields of RCTs from the 2 searching methods were compared for all journals and for each journal individually. RESULTS: No clear motivation for participation in this work could be ascertained because of the low response rates from BAEM and SAEM (10.1% and 1.8%, respectively). Only 18 (29.0%) of the 62 journals identified were indexed by MEDLINE. In the 14 journals indexed by MEDLINE for which hand searching was completed, a total of 710 RCTs were identified by a combination of the 2 approaches; of these, 592 (83.4%) were identified by hand searching alone and 483 (68.0%) by MEDLINE searching alone. Both methods identified 365 (51. 4%) RCTs; hand searching revealed an additional 227 (32.0%) that were not identified by MEDLINE searching, and MEDLINE searching found 118 (16.6%) that were not identified by hand searching. The difference between the proportions identified by hand searching and by MEDLINE searching (15.4%; 95% confidence interval [CI], 12.7% to 17.9%) was statistically significant (McNemar's chi2 test, 1 df, 33. 8; P <.0001). This difference was not significant for 8 of the journals. CONCLUSION: The response rates from mailing to members of the relevant professional organizations letters requesting participation in this work were very low and suggested that such an approach was not cost-effective. However, no formal costing exercise was undertaken. Searching results showed that, in the 14 emergency medicine journals indexed by MEDLINE for which hand searching was completed, hand searching led to identification of additional RCTs (primary articles) not found through MEDLINE searching. However, hand searching, although statistically significantly better than MEDLINE searching, failed to identify some of the RCTs found by MEDLINE searching, suggesting that hand searching is not a "gold standard" method and that the dual approach, promoted by the Cochrane Collaboration, may be the optimal approach for journals indexed by MEDLINE.
Adjuvant chemotherapy and radiation therapy for elimination of residual microscopic non-small cell lung cancer.
This study determined if patients with residual microscopic non-small cell lung cancer (NSCLC) following lung resection treated with combination chemotherapy and radiation realize prolonged survival. Ten men with microscopic NSCLC following resection were given chemotherapy and radiation therapy. Four (40%) of the ten patients were disease-free at 45 months and fully functional. Only two (20%) of the patients died of recurrent lung cancer. Of patients who died of lung cancer, recurrence occurred within five months of treatment and death occurred within one year. The findings suggest combination chemotherapy and radiation therapy delay or prevent recurrence from residual microscopic NSCLC following lung resection.
A child with hemimegalencephaly, hemihypertrophy, macrocephaly, cutaneous vascular malformation, psychomotor retardation and intestinal lymphangiectasia--a diagnostic dilemma.
Although the clinical delineation of the majority of overgrowth syndromes is straightforward, we believe there is a subset of patients with overlapping features from a number of overgrowth syndromes. We report a patient with hemimegalencephaly, hemihypertrophy, macrocephaly, vascular lesions, psychomotor retardation and intestinal lymphangiectasia. The clinical history and findings posed a diagnostic dilemma as the features overlapped between several conditions, namely macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC), Klippel-Trenaunay-Weber syndrome (KTWS), Proteus syndrome and a provisional unique syndrome described by Reardon et al. (1996, Am J Med Genet 66:144-149). We anticipate that only when the molecular basis is delineated will it become clear whether these disorders are separate entities or merely differing ends of the same spectrum.
A multidisciplinary study investigating radiotherapy in Ewing's sarcoma: end results of POG #8346. Pediatric Oncology Group.
PURPOSE: To determine if involved field radiation (IF) is equivalent to standard whole bone radiation (SF) in local tumor control; to establish patterns of failure following treatment; and to determine response, event-free survival (EFS), and overall survival rates from multidisciplinary therapy in Ewing's sarcoma. METHODS AND MATERIALS: Between 1983 and 1988, 184 children with Ewing's sarcoma were enrolled onto Pediatric Oncology Group 8346 (POG 8346). A total of 178 (97%) met eligibility criteria; 6 had pathology other than Ewing's sarcoma. Induction chemotherapy of cyclophosphamide/doxorubicin (adriamycin )(C/A) x 12 weeks was followed by local treatment either surgery or radiation therapy and C/A, dactinomycin, and vincristine for 50 weeks. Resection was advised for patients with small primary tumors if accomplished without functional loss. Forty patients were randomized to receive SF, whole bone radiation to 39.6 Gy plus a 16.2 Gy boost (total 55.8 Gy) or IF to 55.8 Gy, and the remainder were assigned to IF radiation. RESULTS: Of 178 eligible patients, 141 (79%) had localized disease and 37 (21%) had metastases at presentation. Their 5-year EFS was 51% (SE 5%) and 23% (SE 7%) respectively. The response rate to induction chemotherapy was 88% (28% complete, 60% partial), but after radiotherapy the response rate increased to 98%. Thirty-seven of the localized patients underwent resection, of whom 16 (43%) required postoperative radiotherapy; the 5-year EFS of these surgical patients was 80% (SE 7%). The remaining 104 localized patients were eligible for randomization or assignment to receive radiotherapy; the 5-year EFS of these patients was 41% (SE 5%), with no significant difference in EFS between those randomized to SF vs. IF. Site of primary tumor correlated with 5-year EFS: distal extremity 65% (SE 8%), central 63% (SE 10%), proximal extremity 46% (SE 8%), and pelvic-sacral 24% (SE 10%) (p=0.004). Initial tumor size did not correlate significantly with EFS. Patterns of failure among the 141 localized patients revealed 23% of patients experienced a local failure, while 40% had a systemic failure. The 5-year local control rate for the surgical patients +/- postoperative radiotherapy was 88% (SE 6%), while for the patients undergoing radiotherapy alone it was 65% (SE 7%). There was no difference in local control between those randomized to SF vs. IF. The 5-year local control rate for the patients with pelvic-sacral tumors was 44% (SE 15%), significantly worse than the local control rates for those with central tumors 82% (SE 8%), distal extremity 80% (SE 8%), or proximal extremity 69% (SE 9%) (p=0.023). However, quality of radiotherapy correlated with outcome. Patients who had appropriate radiotherapy had a 5-year local control of 80% (SE 7%), while those with minor deviations had 5-year local control of 48% (SE 14%), and those with major deviations had a local control of only 16% (SE 15%) (p=0.005). The local failure was within an irradiated volume in 62% of patients, outside the irradiated volume in 24% of cases, while the precise location could not be determined in the remaining 14%. CONCLUSIONS: As most failures in Ewing's sarcoma are systemic, improved EFS requires more effective systemic chemotherapy. Adequate IF radiotherapy requires treatment to appropriate volumes as defined by MRI imaging and full radiation doses. Pretreatment review of radiologic images with a musculoskeletal radiologist to determine appropriate tumor volumes, as well as use of conformal radiotherapy techniques are important for improved outcome.
Are rural general practitioner--obstetricians performing too many prenatal ultrasound examinations? Evidence from western Labrador.
OBJECTIVE: To determine the frequency of prenatal ultrasonography (PNU) in western Labrador in 1994, assess the appropriateness of the ultrasound examinations according to current guidelines and determine whether there was any relation between number of PNU examinations and patient management and obstetric outcomes. DESIGN: Review of all obstetric charts and PNU requisition forms for all deliveries in one hospital in 1994. SETTING: Labrador City and Wabush, Newfoundland. RESULTS: During the study period, there were 103 singleton deliveries, and these mothers underwent a total of 225 PNU studies (mean 2.16 studies per delivery). More than half (53.3%) of the examinations were classified as inappropriate. There were no significant differences in the number of studies between low- and high-risk pregnancies or between uncomplicated deliveries and those in which induction or instrumental or operative delivery occurred, nor was there any relation between number of PNU examinations and maternal or neonatal outcome. CONCLUSION: Compared with PNU use as recommended by the Canadian Task Force on the Periodic Health Examination, this type of examination was overused in Labrador City and Wabush, although the rate of use was comparable to that reported in other Canadian studies. This overuse was not associated with any identifiable effect on maternal or neonatal outcome or on the management of pregnancy and labour. More judicious use of PNU, in accordance with evidence-based guidelines, is recommended.
Finding out about filling-in: a guide to perceptual completion for visual science and the philosophy of perception.
In visual science the term filling-in is used in different ways, which often leads to confusion. This target article presents a taxonomy of perceptual completion phenomena to organize and clarify theoretical and empirical discussion. Examples of boundary completion (illusory contours) and featural completion (color, brightness, motion, texture, and depth) are examined, and single-cell studies relevant to filling-in are reviewed and assessed. Filling-in issues must be understood in relation to theoretical issues about neural-perceptual isomorphism and linking propositions. Six main conclusions are drawn: (1) visual filling-in comprises a multitude of different perceptual completion phenomena; (2) certain forms of visual completion seem to involve spatially propagating neural activity (neural filling-in) and so, contrary to Dennett's (1991; 1992) recent discussion of filling-in, cannot be described as results of the brain's "ignoring an absence" or "jumping to a conclusion"; (3) in certain cases perceptual completion seems to have measurable effects that depend on neural signals representing a presence rather than ignoring an absence; (4) neural filling-in does not imply either "analytic isomorphism" or "Cartesian materialism," and thus the notion of the bridge locus--a particular neural stage that forms the immediate substrate of perceptual experience--is problematic and should be abandoned; (5) to reject the representational conception of vision in favor of an "enactive" or "animate" conception reduces the importance of filling-in as a theoretical category in the explanation of vision; and (6) the evaluation of perceptual content should not be determined by "subpersonal" considerations about internal processing, but rather by considerations about the task of vision at the level of the animal or person interacting with the world.
A model for estimating the cost-utility of clinical audit. The example of thrombolysis for suspected acute myocardial infarction.
Economic evaluation of quality assurance programs is often called for but rarely reported. A study was designed to estimate the cost-utility of audit of thrombolysis in four U.K. district general hospitals, using the quality-adjusted life year. Although the results obtained were imprecise, the model used could be applied in future evaluations.
CAG repeat expansion in autosomal dominant familial spastic paraparesis: novel expansion in a subset of patients.
Autosomal dominant familial spastic paraplegia (FSP) is a genetically heterogeneous neurodegenerative disorder displaying anticipation for which three loci have been mapped to the chromosomal positions 14q11.2-q24.3 (SPG3), 2p21-p24 (SPG4) and 15q11.1 (SPG6). The repeat expansion detection (RED) method has been used to demonstrate expanded CAG repeats in some FSP families that map to SPG4. We analyzed 20 FSP families, including four for which there is evidence for linkage to SPG4, and found that in most cases the repeat expansion detected by RED is due to non-pathogenic expansions of the chromosome 18q21.1 SEF2-1 or 17q21.3 ERDA1 locus. Polymorphic expansions at SEF2-1 and ERDA1 appear frequent and may confound RED studies in the search for genes causing disorders demonstrating anticipation. In six FSP families, however, CAG repeat expansion was detected in a subset of affected and at-risk individuals that did not result from expansion of the SEF2-1 and ERDA1 loci. Overall, 11 of 37 (30%) of the FSP patients with a CAG/CTG repeat expansion are unaccounted for by the SEF2-1 and ERDA1 loci, compared with two of 23 (9%) of the unaffected at-risk individuals and none of 19 controls. In the majority of cases these novel expansions were shorter than those previously reported.