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Biomedical subjects

N Morton

Publications and source records attributed to N Morton.

At least 19 recordsLinked to original sources

Implicit cognition is impaired and dissociable in a head-injured group with executive deficits.

Implicit or non-conscious cognition is traditionally assumed to be robust to pathology but Gomez-Beldarrain et al. recently showed deficits on a single implicit task after head injury. Laboratory research suggests that implicit processes dissociate. This study therefore examined implicit cognition in 20 head-injured patients and age- and IQ-matched controls using a battery of four implicit cognition tasks: a serial reaction time task (SRT), mere exposure effect task, automatic stereotype activation and hidden co-variation detection. Patients were assessed on an extensive neuropsychological battery, and MRI scanned. Inclusion criteria included impairment on at least one measure of executive function. The patient group was impaired relative to the control group on all the implicit cognition tasks except automatic stereotype activation. Effect size analyses using the control mean and standard deviation for reference showed further dissociations across patients and across implicit tasks. Patients impaired on implicit tasks had more cognitive deficits overall than those unimpaired, and a larger dysexecutive self/other discrepancy (DEX) score suggesting greater behavioural problems. Performance on the SRT task correlated with a composite measure of executive function. Head injury thus produced heterogeneous impairments in the implicit acquisition of new information. Implicit activation of existing knowledge structures appeared intact. Impairments in implicit cognition and executive function may interact to produce dysfunctional behaviour after head injury. Future comparisons of implicit and explicit cognition should use several measures of each function, to ensure that they measure the latent variable of interest.

Adult↗

Remifentanil vs fentanyl/morphine for pain and stress control during pediatric cardiac surgery.

BACKGROUND: Remifentanil is a short acting, potent synthetic opioid that does not accumulate after infusion or repeated bolus doses. It may be rapidly titrated to the requirements of individual patients. Titrated infusion of remifentanil may be able to provide potent analgesia required for pediatric cardiac surgery and obtund the stress response in theater whilst not having the persistent respiratory depression and sedation seen with longer acting opioids. METHODS: Twenty patients were randomized to receive a titrated infusion of remifentanil (0-1 microg x kg(-1) x min(-1)) or a standard dose of fentanyl (30 microg x kg(-1)) prebypass plus morphine (1 mg x kg(-1)) on rewarming. Blood samples for glucose and cortisol were taken at regular intervals from induction through bypass and into the first 24 h of postoperative intensive care. In addition to biochemical indicators of the stress response we recorded baseline hemodynamic parameters and any acute physiological events. RESULTS: Ten patients received morphine, seven received remifentanil. There were no statistically significant differences between the two treatment groups in cortisol measurements, mean arterial pressure or heart rate recordings. In the last time period the remifentanil group had a larger rise in blood glucose concentration (baseline 3.9, rise 3 mmol x l(-1)) than the fentanyl/morphine group (baseline 4.2 rise 1.9 mmol x l(-1)), CI -4.3 to -0.2. CONCLUSIONS: The only significant difference was in glucose in the postbypass time periods. Although statistically significant, this difference is insufficient evidence of increased stress in the remifentanil group. The results show that in the patients studied there was no clinically important difference between the two techniques.

Analgesics, Opioid↗

The evaluation of liquid-based 'Cyto-SED' cytology of bronchioalveolar lavage specimens in the diagnosis of pulmonary neoplasia against conventional direct smears.

Historically, bronchioalveolar lavage (BAL) samples have been prepared by a direct smear (DS) technique. Recent advances in liquid-based cytology have led to a revolution in cytological specimen preparation. Cyto-SED system (CS) is a manual liquid-based cytology system, designed for small-scale use. A total of 137 samples from patients with radiographically detectable lesions underwent BAL procedures at Papworth Hospital NHS Trust over a 4-month period. After preparation for diagnostic purposes with the DS method, the remaining sample was prepared using the CS system. The slides produced were allocated a blind study number and screened by three independent screeners. The cellular morphology was well preserved and comparable between both techniques. Of the 137 patients, 38% were confirmed as malignant by cytology or histology; 71% of these malignant diagnosis were confirmed by the DS technique and 91% confirmed by the CS. The results demonstrate that the CS is a viable alternative to the DS technique. The cytological detail is clearly defined without a loss of three-dimensional information, thus aiding the differential diagnosis of malignancy. Cyto-SED cytology system yields a higher diagnostic accuracy than the conventional direct smear technique without compromising on cytological detail.

Bronchoalveolar Lavage↗

The addition of antiemetics to the morphine solution in patient controlled analgesia syringes used by children after an appendicectomy does not reduce the incidence of postoperative nausea and vomiting.

BACKGROUND: We studied the effect of intraoperative ondansetron 0.1 mg x kg(-1) or droperidol 0.01 mg.kg-1, followed by the same dose of the antiemetic agent added to the morphine solution during patient controlled analgesia (PCA) on the incidence of nausea and vomiting in children following an appendicectomy. METHODS: Sixty children, aged 5-13 years, were recruited and randomly allocated to receive no prophylactic antiemetic, the control group (group C), ondansetron (group O) or droperidol (group D). The PCA pump was programmed to deliver a bolus dose of 20 microg x kg(-1) of morphine.with a 5-min lockout period and a background infusion of 4 microg x kg(-1) x h(-1). RESULTS: Postoperatively, the three groups were compared for nausea, vomiting and sedation scores for 24 h. The incidence of postoperative nausea and vomiting was 33% for group C, 44% for group O and 41% for group D. There was no increase in sedation scores in the droperidol group. CONCLUSIONS: We were unable to show any significant benefit from the prophylactic administration of ondansetron or droperidol to children using morphine PCA devices following appendicectomy in the doses we employed.

Analgesia, Patient-Controlled↗

The Src family tyrosine kinase Fyn regulates natural killer T cell development.

T lymphocytes express two Src tyrosine kinases, Lck and Fyn. While thymocyte and T cell subsets are largely normal in fyn(-/-) mice, animals lacking Lck have impaired T cell development. Here, it is shown that Fyn is required for the rapid burst of interleukin (IL)-4 and IL-13 synthesis, which occurs promptly after T cell receptor activation. The lack of cytokine induction in fyn mutant mice is due to a block in natural killer (NK) T cell development. Studies using bone marrow chimeras indicate that the defect behaves in a cell-autonomous manner, and the lack of NK T cells is probably not caused by inappropriate microenvironmental cues. Both NK T cells and conventional T cells express similar levels of Lck, implying that Fyn and Lck have distinct roles in regulating NK T cell ontogeny. The fyn mutation defines the first signaling molecule that is selectively required for NK T cell, but not for T lymphocyte or NK cell development.

Animals↗

Mistreatment due to weight: prevalence and sources of perceived mistreatment in women and men.

OBJECTIVE: Previous research has documented prejudicial attitudes and discrimination against overweight people. Yet the extent to which overweight people themselves perceive that they have been mistreated because of their weight has not been carefully studied. The purpose of this study was to examine the prevalence of perceived mistreatment due to weight and sources of perceived mistreatment. METHODS AND PROCEDURES: A non-clinical sample of healthy adults (187 men and 800 women) enrolled in a weight gain prevention program comprised the study population. A self-administered questionnaire was used to measure perceived mistreatment due to weight. RESULTS: Overall, 22% of women and 17% of men reported weight-related mistreatment. The most commonly reported sources of mistreatment among women were strangers (12.5%) and a spouse or loved one (11.9%). Men were most likely to report mistreatment by a spouse or loved one (10.2%) and friends (7.5%). Somewhat surprisingly, sex differences in perceived weight-related mistreatment were significant only for stranger as the source. Perceived weight-related mistreatment was positively associated with body mass index (BMI) (r = 0.39, p<0.0001). Reported mistreatment was nearly ten times as pervalent among individuals in the highest quartile of the BMI distribution (42.5%) than among those in the lowest BMI quartile (5.7%), but was significantly greater than zero in all but the very lean. DISCUSSION: Perceived mistreatment due to weight is a common experience and is not restricted to the morbidly obese. Results are discussed in light of the sociocultural value for thinness.

Adult↗

Hardy-Weinberg quality control.

An efficient test of deviation from Hardy-Weinberg frequencies with one degree of freedom was applied to 44 marker loci in a genome scan, and 7 loci had a significant excess of apparent homozygotes (chi2 (1) > 6) suggestive of typing error. In this example evidence for linkage did not increase when outliers were censored. Statistical quality control is an essential part of genotyping, and the effect of mistyping and map error should be considered in evaluating any genome scan.

Asthma↗

Association between - 308 tumour necrosis factor promoter polymorphism and bronchial hyperreactivity in asthma.

BACKGROUND: Tumour necrosis factor (TNF) is a pivotal cytokine in the inflammation underlying asthma. The TNF gene is located in the polymorphic HLA class 3 region on chromosome 6p. Several polymorphisms in this region have been described and associated with alteration of TNF secretion in vitro. OBJECTIVE: In this study we tested the hypothesis that two such polymorphisms, lymphotoxin alpha NcoI B*1 and -308 TNF2 may be components of the genetic predisposition to asthma. METHODS: Five hundred and fifty-six random individuals were studied, comprising approximately equal numbers of asthmatic subjects, with or without atopy, and a nonatopic nonasthmatic control group. In addition, 355 subjects (172 asthmatics) from 60 multiplex families were typed at the LTalpha NcoI locus. RESULTS: There was an association between allele two of the -308 TNF polymorphism and bronchial hyperreactivity (OR 2.12, 95% CI 1.04-4.32, P = 0.036). However, there was no association with LTalpha NcoI alleles. To determine whether this was influenced by linkage disequilibrium within the MHC, 91 subjects with bronchial hyperreactivity and 85 control subjects were typed for class 2 and 3 alleles. Following identification of the extended TNF2 haplotype, we found no independent association of these alleles with BHR. CONCLUSIONS: We conclude that the -308 TNF2 promoter polymorphism may form a component of the genetic predisposition to BHR in asthma.

Adolescent↗

A new cancer education mission: managed care and clinical trials.

BACKGROUND: The traditional support for clinical research, teaching, and indigent patient care is being seriously compromised by the growth of managed care in the United States. Educational initiatives are needed to ensure the incorporation of clinical trials into the optimal care of cancer patients. METHODS: The Cancer Clinical Trials Task Force of Colorado was established in 1995 to find a collaborative and non-legislative solution to the uncertainty of coverage by third-party payers for cancer patients participating in clinical trials. RESULTS: This program has served to heighten the awareness of the crucial role of clinical trials in defining new treatment strategies among third-party payers. CONCLUSIONS: The Task Force and similar regional and national efforts have begun to provide needed information and education about the importance of clinical trials to the managed care industry; however, much remains to be done to ensure access to and coverage for clinical trials.

Clinical Trials as Topic↗

Microdeletions in FMR2 may be a significant cause of premature ovarian failure.

Genetic causes of premature ovarian failure (POF) include X chromosome deletions and fragile X (FRAXA) premutations. While screening a cohort of women with POF for FRAXA premutations, a more distal trinucleotide repeat, FRAXE, was also tested. We found an unexpected excess of FRAXE alleles with apparently fewer than 11 repeats in the POF group. However, sequence analysis of these alleles showed that the excess was caused by three females who carry cryptic deletions in FMR2, the gene associated with FRAXE. We propose that microdeletions within FMR2 may be a significant cause of premature ovarian failure, being found in 1.5% of women with the condition, and in only 0.04% of the general female population. The deletions may affect transcription of either FMR2 or an adjacent gene.

Adult↗

Linkage of asthma to markers on chromosome 12 in a sample of 240 families using quantitative phenotype scores.

We present evidence of linkage between markers on chromosome 12 and asthma using the BETA program for nonparametric single- and multipoint linkage analysis. We have used quantitative scores as our phenotypic variables, combining data into indices for asthma and atopy and maximizing heritability. The largest single-locus LODs were achieved for asthma: D12S342 and asthma score (LOD 2.255), D12S324 and asthma affection (LOD 2.214), and D12S366 and wheeze (LOD 3.307). The region of interest identified using multipoint analysis, with a maximum LOD of 2.29, centers around D12S97 at location 173.5 cM with a standard error of 6.5 for the asthma score and close agreement for asthma affection and wheeze. Such evidence merits further investigation of this area in an attempt to define the region with greater precision with a view to identifying candidate genes. We hope that the methods presented will encourage researchers to use phenotypic information in a way that encourages meta-analysis.

Adolescent↗

Theory and observation of attachment and its relation to child maltreatment: a review.

OBJECTIVE: The aim of this paper was to review the literature on attachment and child maltreatment in relation to the intergenerational transmission of maltreatment. METHOD: A review of the literature to date was undertaken, and a descriptive analysis of 13 studies on the quality of attachment in maltreated samples was conducted. RESULTS: Quality of infant attachment seems to be in the most part dependent upon the sensitiveness of the mother. Not surprisingly the majority of studies demonstrates that on average maltreated children are less securely attached to their mothers than nonmaltreated children. This early mother-infant relationship is said to be internalized by the child and consequently form a prototype to which all future relationships are assimilated. Thus maltreated children may have problems forming relationships with peers, partners and their own children. CONCLUSIONS: It is suggested that this is the primary process by which maltreatment continues from one generation to the next. The implications of this process for the prediction and prevention of childhood maltreatment are discussed.

Child↗

Non-disjunction of chromosome 18.

A sample of 100 trisomy 18 conceptuses analysed separately and together with a published sample of 61 conceptuses confirms that an error in maternal meiosis II (MII) is the most frequent cause of non-disjunction for chromosome 18. This is unlike all other human trisomies that have been studied, which show a higher frequency in maternal meiosis I (MI). Maternal MI trisomy 18 shows a low frequency of recombination in proximal p and medial q, but not the reduction in proximal q observed in chromosome 21 MI non-disjunction. Maternal MII non-disjunction does not fit the entanglement model that predicts increased recombination, especially near the centromere. Whereas recent data on MII trisomy 21 show the predicted increase in recombination proximally, maternal MII trisomy 18 has non-significantly reduced recombination. Therefore, chromosome-specific factors must complicate the simple model of susceptible chiasma distributions interacting with age-dependent deterioration of the meiotic mechanism. For chromosome 18, 30% of tetrads are nullichiasmate in maternal MI non-disjunction, but nullichiasmates are not observed in maternal MII non-disjunction. Chiasma distributions from normal chromosome 18 meioses provide no evidence for normal disjunction from nullichiasmate tetrads. We extend this study to examine the remaining autosomes and find no evidence for normal disjunction from nullichiasmate tetrads generally.

Age Factors↗

Atopy phenotype.

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Genetic Variation↗

The glutamine 27 beta2-adrenoceptor polymorphism is associated with elevated IgE levels in asthmatic families.

BACKGROUND: The beta2-adrenoceptor polymorphisms occurring at amino acid positions 16 (arginine to glycine) and 27 (glutamine to glutamate) are known to be functionally relevant and also disease-modifying in subjects with asthma. However, the contribution of these polymorphisms to the development of the asthmatic phenotype or other markers for allergic disease remains to be established. OBJECTIVE: This large family study examines the contributions of these polymorphisms in determining the heritable component of markers for allergic disease in asthmatic families. METHODS: Three hundred twenty-four individuals from 60 families multiplex for asthma selected by means of an asthmatic proband were characterized for the following markers of allergic disease: asthma, atopy, and serum IgE. The polymerase chain reaction was used to generate a 234 base pair fragment spanning the region of interest, and the beta2-adrenoceptor polymorphism was then defined by allele-specific oligonucleotide hybridization. Segregation analysis was then performed. RESULTS: We found a significant association (p = 0.009) between the glutamine 27 beta2-adrenoceptor polymorphism and elevated levels of IgE, which was supported by the observation of linkage between IgE and beta2-adrenoceptor polymorphisms at locus 27 (p = 0.037). However, there was no association between either the arginine-glycine 16 or the glutamine-glutamate 27 beta2-adrenoceptor polymorphism and an increased risk of asthma or atopy per se. CONCLUSION: The glutamine 27 beta2-adrenoceptor polymorphism appears to contribute to IgE variability in families with asthma. However, it seems that although both amino acid 16 and 27 beta2-adrenoceptor polymorphisms are disease-modifying in subjects with asthma, they do not contribute markedly to the development of the asthmatic phenotype.

Adult↗

Leg ulceration and ethnicity: a study in west London.

Little is known of the influence race has on the development of leg ulceration, with most studies being performed in almost exclusively white populations. As part of a wider audit of leg ulcer services, health care professionals were contacted to give details of age, sex and ethnic background of all patients who attended for treatment of leg ulceration over a one year period in an area of west London. West London Health Care Trust provides services to a population of 275,000 of whom 53,000 have an ethnic background from the Indian subcontinent (South Asian). In all, 280 patients were identified, of whom 264 (94%) had details of age and sex. This gave a crude ascertainment rate of 1.02 per 1000 population. Of the 264 patients, five were classified as South Asians, with one patient classified as Afro-caribbean. The Mantel Haenzsel test demonstrated a significantly higher proportion of whites suffering from leg ulceration than South Asians, giving an odds ratio of 4.43, with 95% confidence intervals between 1.94 and 10.13 (P = 0.0004). The expected frequency of South Asian patients should be 23, based on rates from the white population, of which 13 would be women and 10 men. Only five South Asian men were identified, and no Asian women with leg ulceration. Reasons for this low ascertainment are two-fold. Either there is a real difference between the white and South Asian populations, or South Asian patients are not presenting for treatment. Further work must be performed to determine whether this is an effect of low prevalence, or unmet need in the community.

Aged↗