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Biomedical subjects

D McGuinness

Publications and source records attributed to D McGuinness.

At least 19 recordsLinked to original sources
PubMed2001

Frequent and persistent, asymptomatic Plasmodium falciparum infections in African infants, characterized by multilocus genotyping.

To determine the duration and complexity of naturally acquired Plasmodium falciparum infections in small children, a longitudinal cohort study of 143 newborns was conducted in coastal Ghana. On average, children experienced 2 episodes of infection in their first 2 years of life, the median duration of an asymptomatic infection was <4 weeks, and estimates of the mean number of parasite genotypes per infection were 1.15-2.28. Nevertheless, 40% of the children experienced infections lasting </=12 weeks, and both the duration and complexity of infections increased with age. The longest period of continual infection was 64 weeks, and the maximum persistence of a single parasite genotype was 40 weeks. Thus, malaria infections in infants <5 months old tend to be asymptomatic and rapidly cleared; persistent asymptomatic parasitemia is more common in children >5 months old. The ability of very young children to clear or control malaria infections indicates the presence of effective innate or immune antiparasite mechanisms.

Age Factors↗
PubMed2001

Do high-threat life events really provoke the onset of psychiatric disorder in children?

Studies on adults have suggested important effects of stressful life events in provoking onset of psychiatric disorder. Only a few comparable studies on children exist, and their results are inconsistent in relation to definite timing effects. Meeting some important methodological challenges overlooked in the past research, this study set out to examine whether the onset of psychiatric disorder in children was more likely to occur shortly after a severe event, as compared with other times. The sample consisted of 99 consecutive, newly referred patients, aged 8-16 years, from a child psychiatry service in London. PACE (Psychosocial Assessment of Childhood Experiences), an investigator-based, standardized interview was used to assess the timing and impact of life events over the preceding 18 months. CAPA (Child and Adolescent Psychiatric Assessment), a standardized diagnostic assessment, was used to establish the presence, timing, and consequential impairment of child and adolescent psychiatric symptoms. In a within-subject, over-time design, conditional logistic regression techniques were employed to examine whether risk of onset was greater in the 9 weeks following a high-threat life event than at other times. There was a small but statistically significant association between child-reported events and child-reported onset; the associations with parent-reported onset were inconsistent. Parent-reported events failed to relate to onset by either source. The study offers only quite limited support to the notion of negative life events provoking onset of psychiatric disorder in children and young people. The possible reasons for this are discussed, together with important conceptual and methodological issues to problems of defining onset, and the choice of appropriate designs for data analysis.

Adolescent↗
PubMed2000

The role of acute and chronic stress in asthma attacks in children.

BACKGROUND: High levels of stress have been shown to predict the onset of asthma in children genetically at risk, and to correlate with higher asthma morbidity. Our study set out to examine whether stressful experiences actually provoke new exacerbations in children who already have asthma. METHODS: A group of child patients with verified chronic asthma were prospectively followed up for 18 months. We used continuous monitoring of asthma by the use of diaries and daily peak-flow values, accompanied by repeated interview assessments of life events and long-term psychosocial experiences. The key measures included asthma exacerbations, severely negative life events, and chronic stressors. FINDINGS: Severe events, both on their own and in conjunction with high chronic stress, significantly increased the risk of new asthma attacks. The effect of severe events without accompanying chronic stress involved a small delay; they had no effect within the first 2 weeks, but significantly increased the risk in the subsequent 4 weeks (odds ratio 1.71 [95% CI 1.04-2.82], p < or = 0.05 for weeks 2-4 and 2.17 [1.32-3.57], p < or = 0.01 for weeks 4-6). When severe events occurred against the backdrop of high chronic stress, the risk increased sharply and almost immediately within the first fortnight (2.98 [1.20-7.38], p < or = 0.05). The overall attack frequency was affected by several factors, some related to asthma and some to child characteristics. Female sex, higher baseline illness severity, three or more attacks within 6 months, autumn to winter season, and parental smoking were all related to increased risk of new exacerbations; social class and chronic stress were not. INTERPRETATION: Severely negative life events increase the risk of children's asthma attacks over the coming few weeks. This risk is magnified and brought forward in time if the child's life situation is also characterised by multiple chronic stressors.

Acute Disease↗
PubMed2000

Lack of association between maternal antibody and protection of African infants from malaria infection.

Maternally derived antibodies are believed to protect infants against infection, but there is little direct evidence for a protective role of passively acquired antibodies against malaria. A longitudinal study of malaria infection in 143 infants was conducted in a region of southern Ghana where Plasmodium falciparum is endemic. Infants born in the high-transmission season were less likely to become infected in the first 20 weeks of life than children born in the low-transmission season. Plasma, obtained at birth, was tested for immunoglobulin G (IgG) and IgG subclasses to P. falciparum schizonts and recombinant circumsporozoite antigen, MSP-1(19), MSP-2, AMA-1, and Pf155 (also called ring-infected erythrocyte surface antigen). Antibody levels at birth were not associated with resistance to malaria infection. On the contrary, antibodies at birth were positively associated with infection, indicating that high levels of maternally derived antibodies represent a marker for intensity of exposure to malaria infection in infants. However, all five children who experienced high-density infections (>100 parasites/microl of blood) were seronegative for MSP-1(19) at the time of infection.

Adolescent↗
PubMed1999

Transmission-blocking immunity to Plasmodium falciparum in malaria-immune individuals is associated with antibodies to the gamete surface protein Pfs230.

Malaria-immune human sera were tested for their ability to affect the infectivity of Plasmodium falciparum gametocytes to Anopheles stephensi mosquitoes. Transmission-reducing effects of the sera were associated with the presence of antibodies to the gamete surface protein, Pfs230. Enhancement of transmission, manifest as elevated numbers of oocysts relative to controls, was observed for a number of sera, but was not found to be associated with antibodies against Pfs230. These results confirm that Pfs230 is a possible candidate for inclusion in a transmission-blocking malaria vaccine.

Animals↗
PubMed1999

TNFalpha*2 marks high risk of severe disease during Plasmodium falciparum malaria and other infections in Sri Lankans.

We have investigated the association between alleles of the genes for tumour necrosis factor-alpha (TNF-alpha) and TNF-beta and severity of disease during malarial (Plasmodium falciparum) and other infections in the Sri Lankan population. Patients were categorized as having either (i) uncomplicated malaria, (ii) severe and complicated malaria, or (iii) severe and complicated infection in which a diagnosis of malaria had been excluded. For all the patients, as well as for a group of matched healthy controls, TNF-alpha and TNF-beta allelic types were identified using the polymerase chain reaction (PCR) and allele-specific oligonucleotide probes and restriction enzyme digestion. The odds in favour of carrying the TNFalpha*2 allele, mainly of the heterozygous genotype (TNFalpha*1,*2), were two to three times greater among individuals with severe disease, of either malarial or other infectious origin, relative to healthy controls or to those with uncomplicated malarial infections. No significant risk was associated with either of the alleles of TNF-beta.

Alleles↗
PubMed1998

Contrasting child and adolescent psychiatry services in Szeged, Hungary, and Glasgow, Scotland.

International comparisons of child and adolescent psychiatry services are rarely reported in the literature. The present study arose out of a TEMPUS collaborative project between the University Departments of Child and Adolescent Psychiatry in Szeged, Hungary, and Glasgow, Scotland. Using the Glasgow Audit Questionnaire, a profile of each service was obtained, including basic demographic data, types of disorders referred, treatment modalities used, and a measure of outcome. The results of this descriptive study indicate that although the two centres were broadly similar, there were major differences in the treatment modalities used. Reasons for the findings are discussed, as are the limitations of the study.

Adolescent↗
PubMed1998

Independence of childhood life events and chronic adversities: a comparison of two patient groups and controls.

OBJECTIVE: To examine the differences between independent and behavior-dependent stressful life events and chronic adversities in child psychiatric patients, community controls, and children with asthma. METHOD: The Psychosocial Assessment of Childhood Experiences was used to assess recent severe events (life events with high long-term threat) and major adversities (long-term experiences with high negative impact on child) in children attending a psychiatric clinic (n = 99), community controls (n = 26), and children with chronic asthma (n = 94). RESULTS: In the previous year, the psychiatric patients had, on average, experienced significantly more independent and behavior-dependent severe events and major adversities than either the controls or the asthmatic patients. The differences were most pronounced in relation to behavior-dependent high-threat life events and long-term-experiences. Among the psychiatric patients, one third of all severe events and one quarter of all major adversities were dependent on the child's behavior. The corresponding proportions in the controls and children with asthma were between one fifth and one twelfth. CONCLUSIONS: Psychiatrically disturbed children have an increased risk of experiencing behavior-dependent life events and long-term adversities compared with their peers in the community at large and compared with children suffering from a chronic physical illness such as asthma. Future studies need to examine the possible contributions of such experiences to the development and maintenance of psychiatric and physical illness in children.

Adolescent↗
PubMed1998

High incidence of asymptomatic malara infections in a birth cohort of children less than one year of age in Ghana, detected by multicopy gene polymerase chain reaction.

The incidence of Plasmodium falciparum infection has been followed in a birth cohort of 71 infants in southern Ghana, an area of perennial malaria transmission. Parasite DNA detection established the presence of a high rate of infection in newborns (13.6%), a low level of infection from two to 26 weeks (1.5-9.7%) and a steadily increasing parasite rate from 26 weeks of age. The median age to first infection was 42 weeks. Five cases of fever (temperature > or = 37.5 degrees C) and parasite density greater than 1,000 parasites/microl of blood, all in children more than 18 weeks of age, were considered possible cases of clinical malaria. The risk of infection was almost three times higher in the wet season than in the dry season and increased significantly from the age of 18 weeks. The level of malaria-specific IgG at birth was positively correlated with risk of infection in children 6-12 months of age, indicating that maternally derived anti-malarial IgG is correlated with exposure to malaria infection. There was no association between malaria-specific IgG at birth and risk of infection in children 0-6 months of age. However, infants do appear to possess mechanisms to limit parasite growth and a role for maternal antibody cannot be ruled out.

Adult↗
PubMed1997

Statistical analysis of highly skewed immune response data.

This paper considers methods of statistical analysis for highly skewed immune response data. Observations from population studies of immunological variables are rarely normally distributed between individuals; typically the distribution shows extreme levels of skewness. In some situations, skewness remains considerable even after transforming the data. Using resampling techniques, applied to several actual datasets of ELISA assay data, we consider the robustness of normal parametric methods, e.g. t tests and linear regression. Despite the skewness of the transformed data, we demonstrate that such methods are quite robust depending on the number of observations, type of analysis and severity of skewness. We also illustrate how bootstrap resampling can be used to provide a valid alternative method of analysis that can be used either for checking normal parametric analysis or as a direct method of analysis. We illustrate this combined approach by analysing real data to test for association between human serum antibodies to malaria merozoite surface proteins, MSP1 and MSP2, and resistance to clinical malaria, and confirm the protective effect of antibodies to MSP1 and demonstrated a similar protective effect for some antibodies to MSP2.

Animals↗
PubMed1997

Complement-mediated lysis of Plasmodium falciparum gametes by malaria-immune human sera is associated with antibodies to the gamete surface antigen Pfs230.

Antibodies to the sexual-stage surface antigens of Plasmodium falciparum, Pfs230 and Pfs48/45, can abolish the infectivity of gametes to mosquitoes; these antigens have been proposed as candidates for inclusion in a malaria transmission-blocking vaccine. One possible mechanism of antibody-mediated transmission blocking is complement-mediated gamete lysis. We have used a panel of human sera from geographically distinct regions where malaria is endemic to investigate whether this may be a mechanism of naturally acquired transmission-blocking immunity to P. falciparum. By immunoprecipitation, we have shown that antibody recognition of Pfs230 and Pfs48/45 is limited, despite universal exposure to P. falciparum gametocytes. In vitro complement-mediated lysis of P. falciparum gametes was positively associated with the presence of antibodies to Pfs230 but not with antibodies to the N-terminal region of the precursor molecule (Pfs260), which is shed from the gametocyte surface at the time of gametogenesis. Similarly, antibodies to two other gametocyte-specific proteins, Pfs48/45 and Pfg27/25, were not associated with gamete lysis. All sera which mediate gamete lysis contain immunoglobulin G1 (IgG1) and/or IgG3 antibodies to gamete surface proteins as determined by an enzyme-linked immunosorbent assay. These data suggest that Pfs230 is a major target of complement-fixing antibodies which may be important for antibody-mediated transmission-blocking immunity.

Adolescent↗
PubMed1996

Selective recognition of malaria antigens by human serum antibodies is not genetically determined but demonstrates some features of clonal imprinting.

Malaria infection induces the production of serum antibodies to a variety of malaria antigens but the prevalence of antibodies to any particular antigen is typically much less than 100%. It has been assumed that non-responsiveness to defined antigens in malaria immune subjects is due to HLS-mediated restriction of the immune response. In this study we have investigated the role of HLA and non-HLA genes in the antibody response to two merozoite surface antigens (MSP1 and MSP2) and a sexual stage antigen (Ps260/230) of Plasmodium falciparum, and conclude that host genotype is not a major determinant of responsiveness. Although antibody levels vary in accordance with seasonal variations in malaria transmission in semi-immune children, antibody levels remain stable in clinically immune adults. Antigen recognition is selective with individual donors showing consistent high titre responses to some antigens/epitopes whilst consistently failing to recognize adjacent regions/epitopes of the same protein. An alternative explanation, consistent with the data presented here, is that selective antibody responses to malaria antigens in immune individuals result from a process akin to clonal imprinting (original antigenic sin).

Adult↗
PubMed1995

Delayed puberty in males with beta-thalassemia major: pulsatile gonadotropin-releasing hormone administration induces changes in gonadotropin isoform profiles and an increase in sex steroids.

Patients with beta-thalassemia major often have pubertal delay, the etiology of which has not been fully elucidated. We investigated the pituitary-gonadal response to short-term subcutaneous pulsatile gonadotropin-releasing hormone (GnRH) administration (150 ng/kg body weight every 120 min for 7 days) in five young males (aged 13.6-19.0 years) affected by beta-thalassemia major and presenting signs of delayed puberty. Immunoreactive and bioactive gonadotropin levels were determined and their isoform profiles were examined, before and after GnRH treatment, in a pool of samples collected every 15 min for 240 min. Testosterone, androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone and 17 beta-estradiol were measured as markers of gonadal function on days 0, 1, 3, 5 and 7 of treatment. Five patients (aged 16.9-26.8 years) with confirmed diagnosis of idiopathic hypogonadotropic hypogonadism who were starting pulsatile GnRH therapy were also studied in the same protocol. Increased sex steroid levels were observed in both groups as a result of treatment. On day 7, the thalassemic patients had increased bioactive luteinizing hormone (LH) and follide-stimulating hormone (FSH), although immunoreactive LH and FSH were comparable to day 0. Moreover, fewer acidic and more basic immunoreactive and bioactive isoforms were noted in LH profiles on day 7. Similar results were observed in hypogonadal patients, who also had increased immunoreactive LH and FSH values. We suggest that the early stage of delayed puberty in thalassemia might be characterized by a neuroendocrine dysfunction resulting in an impaired hypothalamic GnRH release, which is inadequate for a proper pituitary stimulation. Pulsatile GnRH treatment seems to re-establish partially the correct pituitary-gonadal function.

17-alpha-Hydroxyprogesterone↗
PubMed1993

Assessment of psychosocial experiences in childhood: methodological issues and some illustrative findings.

The development of a new standardised investigator-based interview, PACE (Psychosocial Assessment of Childhood Experiences), for the assessment of acute life events and long-term psychosocial experiences is described. An application of PACE to a sample of 84 children referred to psychiatric clinics and 22 general population controls, is presented. Reliability was assessed using a separate clinic sample of 15 child-parent pairs. The findings showed that PACE has satisfactory reliability and discriminant validity.

Adaptation, Psychological↗
PubMed1992

Attention and para-attentional processing. Event-related brain potentials as tests of a model.

In 1972 when we began to analyze the vast amount of material from the laboratories of physiological psychologists, we had only a vague conceptualization of what a model of attention might look like. We began where everyone else had, with the view that everything had something to do with "arousal" but with Lacey's (1967) warning in mind that all of the dependent variables might not actually be measuring aspects of the same process. With this warning in mind, we were forced by the data to organize them into a three-systems mode. Since the first publication of this model in 1975, we have found increasing amounts of evidence to support and extend it. This evidence is briefly reviewed in the present paper in terms of the techniques employed in various types of investigation. Further, the current review of data has made it possible to specify the para-attentional substrate (the extrinsic lemniscal primary projection systems) upon which the three systems described in the earlier model operate. The earlier model was based on psychophysiological, neurobehavioral and neurochemical analyses while the current specification results from the results of recordings of event-related brain electrical responses. The conclusions derived from these results can be summarized as follows: First. It has become possible to distinguish controlled attention from the para-attentional pre- and post-attentive automatic processes upon which controls operate. Second. The pre- and post-attentive processes appear to be coordinate with activity in the extrinsic lemniscal primary sensory projection systems. Processing in these systems is reflected in the early components of event-related brain electrical potentials. These extrinsic systems are, however, not just throughputs for further processing. Rather, they are sensitive to the history of reinforcement which the subject has experienced. The concept of a limited channel capacity must, therefore, be modified to encompass this ability of organisms to improve, through practice, their competence to process a great deal of information in parallel. Competence, not capacity, limits central processing span. Third. A set of intrinsic extralemniscal processing systems has been identified to operate via a tecto-tegmental pathway to the reticular nucleus of the thalamus. The later components (N2P3, etc.) of event-related potentials have been shown to reflect processing in these systems and those that control them. Activity in these systems has been related to targeted conscious awareness.(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗
PubMed1982

Lateral asymmetry: hard or simple-minded?

A letter or a three-dimensional shape was presented in the center of the visual field. Following the off-set of this stimulus either a comparison letter or a three-dimensional shape was flashed briefly in either the right or left visual field. The subject's task was to respond SAME, or DIFFERENT. The stimuli could be in the same plane, rotated in two dimensions (letters) or in three dimensions (three-dimensional shapes). The left visual field presentations (right hemisphere) of same-pair matches for letters only produced faster reaction times and fewer errors. In all other conditions reaction time measures showed no hemisphere effects. By contrast, error score data indicated that the left hemisphere was overwhelmingly more accurate.

Adolescent↗
PubMed1980

A decisional analysis of the effects of inferotemporal lesions in the rhesus monkey.

Modified signal detection procedures were used to analyze the effects of inferotemporal cortical resections. The results demonstrated (a) a severe difficulty in responding to differences in luminance; (b) a severe difficulty in responding to differences in luminance; (b) a small but consistent change in sensitivity (d'), which is attributed to an increased sensitivity to noise or a deficiency in the suppression of irrelevant aspects of the environment; and (c) an enhanced bias to respond to a nonrewarded stimulus (a lowering of criterion). This altered bias contrasts with the results obtained from limbic resections in a previous experiment which produced a marked increase in bias to a rewarded contingency without influencing discrimination or detection.

Animals↗