Assessing children's toxic risks. Pediatricians gain new diagnostic tool.
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Biomedical subjects
Publications and source records attributed to J Morris.
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CENP-C is an evolutionarily conserved centromeric protein. We have used the chicken DT40 cell line to test the idea that CENP-C is sufficient as well as necessary for the formation of a functional centromere. We have compared the effects of disrupting the localization of CENP-C with those of inducibly overexpressing the protein. Removing CENP-C from the centromere causes disassembly of the centromere protein complex and blocks cells at the metaphase-anaphase junction. Overexpressed CENP-C is associated with an increase in errors of chromosome segregation and inhibits the completion of mitosis. However, the excess CENP-C does not disrupt the native centromeres detectably and does not associate with another conserved centromere protein, ZW10. The distribution of the excess CENP-C changes during the cell cycle. In metaphase, the excess CENP-C coats the chromosome arms. At the metaphase-anaphase transition, the excess CENP-C clusters, and during interphase it is present in large bodies which form around pre-existing centromeres which are also clustered. These results indicate that CENP-C is necessary but not sufficient for the formation of a functional centromere and suggest that the structure of CENP-C may be regulated during the cell cycle.
Although the explanation for sudden infant death syndrome (SIDS) remains unknown, an increasing body of evidence now exists to suggest a possible role for bacterial toxins in the aetiology, and a number of investigators have considered that endotoxaemia could explain some of the associated features. Following the development of an animal model which confirmed that endotoxaemia could be detected after death, we studied endotoxin levels in blood and tissue samples taken at autopsy from SIDS infants, child controls and adult controls. There were significant correlations between endotoxin levels in blood and the various organs sampled particularly in SIDS cases and child controls, and blood endotoxin levels in SIDS cases were higher in those infants where there was histological evidence of mild to moderate inflammation. However, overall no significant differences were found between endotoxin levels in blood or tissue in the three study groups. Further studies into possible actions or interactions of endotoxin in SIDS are required.
OBJECTIVES: To investigate the effect of Chlamydia pneumoniae infection on future development of ischaemic heart disease and mortality. DESIGN: Prospective longitudinal study. SETTING: Caerphilly, South Wales. SUBJECTS: Plasma specimens were collected during 1979-83 from 1773 men aged 45-59 years. These were tested for IgG and IgA antibodies to C pneumoniae (TW183) by microimmunofluorescence. OUTCOME MEASURES: 13 year mortality and incident ischaemic heart disease events were ascertained from death certificates, hospital records, and electrocardiographic changes at follow up every 4 to 5 years. RESULTS: 642 men (36.2%) had IgG antibodies at a titre of >/=1 in 16, of whom 362 (20.4% of all men) also had detectable IgA antibodies. The prevalence of ischaemic heart disease (a history of past or current disease) at entry was similar at all IgG antibody titres but was positively related to IgA antibody titre. IgA antibody titre was positively correlated with plasma viscosity but not with other cardiovascular risk factors. Incidence of ischaemic heart disease was not associated with either IgG antibody titre or IgA antibody titre, but there were stronger and significant relations of IgA antibodies with all cause mortality and fatal ischaemic heart disease, which persisted after adjustment for conventional cardiovascular risk factors. The odds ratios associated with detectable IgA antibodies were 1.07 (95% confidence interval 0.75 to 1.53) for all incident ischaemic heart disease, 1. 83 (1.17 to 2.85) for fatal ischaemic heart disease, and 1.50 (1.10 to 2.04) for all cause mortality. CONCLUSION: This is the first prospective demonstration of an association between IgA antibodies to C pneumoniae, a putative marker of chronic infection, and subsequent risk of death from ischaemic heart disease. In contrast to earlier case-control studies, IgG antibodies were not associated with either prevalent or incident ischaemic heart disease.
Recent work on Drosophila oogenesis has uncovered connections between cell-cycle checkpoints and pattern formation. Genes of the spindle class, which encode double-strand break repair enzymes and RNA helicases, affect oocyte polarity and the decision whether to differentiate as an oocyte or a nurse cell.
HYPOTHESIS: Factors associated with fetal death in injured pregnant patients are related to increasing injury severity and abnormal maternal physiologic profile. DESIGN: A multi-institutional retrospective study of 13 level I and level II trauma centers from 1992 to 1996. MAIN OUTCOME MEASURE: Fetal survival. RESULTS: Of 27,715 female admissions, there were 372 injured pregnant patients (1.3%); 84% had blunt injuries and 16% had penetrating injuries. There were 14 maternal deaths (3.8%) and 35 fetal deaths (9.4%). The population suffering fetal death had higher injury severity scores (P<.001), lower Glascow Coma Scale scores (P<.001), and lower admitting maternal pH (P = .002). Most women who lost their fetus arrived in shock (P = .005) or had a fetal heart rate of less than 110 beats/min at some time during their hospitalization (P<.001). An Injury Severity Score greater than 25 was associated with a 50% incidence of fetal death. Placental abruption was the most frequent complication, occurring in 3.5% of patients and associated with 54% mortality. Cardiotrophic monitoring to detect potentially threatening fetal heart rates was performed on only 61% of pregnant women in their third trimester. Of these patients, 7 had abnormalities on cardiotrophic monitoring and underwent successful cesarean delivery. CONCLUSIONS: Fetal death was more likely with greater severity of injury. Cardiotrophic monitoring is underused in injured pregnant patients in their third trimester even after admission to major trauma centers. Increased use of cardiotrophic monitoring may decrease the mortality caused by placental abruption.
There are no clear published data on the risks of bacterial arthritis following intra-articular corticosteroid injections. Forty rheumatologists were given a detailed questionnaire; 32 (response 80%) completed questionnaires were analysed. On the basis of recalled cases of post-injection joint infection we estimate this risk to be low, at 4.6/100,000 injections.
BACKGROUND: Infantile hepatic hemangioma is a benign liver tumor with potentially fatal complications. Response of these lesions to steroid therapy has been well documented in infants. Successful antenatal treatment of a fetal hepatic hemangioma with maternal corticosteroids is reported. CASE: A 36-year-old woman, gravida 2, para 1, had an ultrasound at 17 weeks which showed a fetal hepatic hemangioma. Because of increase of the tumor and enlarged fetal heart, maternal oral corticosteroid therapy was commenced at 28 weeks, which progressively decreased the mass. The infant was delivered at 36 weeks with no evidence of heart failure, and at 7 months the tumor was barely seen on ultrasound. CONCLUSION: When an enlarging fetal hepatic hemangioma is detected antenatally, maternal corticosteroid therapy should be considered.
We have used dogs to study gene transfer into hematopoietic stem cells, because of the applicability of results in dogs to human transplantation and the availability of canine disease models that mimic human diseases. Previously we reported successful gene transfer into canine marrow repopulating cells, however, gene transfer efficiency was low, usually below 0.1% (Kiem et al, Hum Gene Ther 1996; 7: 89). In this study we have used CD34-enriched marrow cells to study different retroviral pseudotypes for their ability to transduce canine hematopoietic repopulating cells. Cells were divided into two equal fractions that were cocultivated for 72 h with irradiated packaging cells producing vector with different retroviral pseudotypes (GALV, amphotropic or 10A1). The vectors used contained small sequence differences to allow differentiation of cells genetically marked by the different vectors. Nonadherent and adherent cells from the cultures were infused into four dogs after a myeloablative dose of 920 cGy total body irradiation. Polymerase chain reaction (PCR) analysis of DNA from peripheral blood and marrow after transplant showed that the highest gene transfer rates (up to 10%) were obtained with the GALV-pseudotype vector. Gene transfer levels have remained stable now for more than 18 months. Southern blot analysis confirmed the high gene transfer rate. Interference studies on canine D17 cells revealed that 10A1 virus behaved like an amphotropic virus and was not able to use the GALV receptor. In summary, our results show improved gene transfer into canine hematopoietic repopulating cells when CD34-enriched cells are transduced by cocultivation on a GALV-pseudotype packaging cell line in combination with a GALV-pseudotype vector. Furthermore, these results demonstrate that the monoclonal antibody to canine CD34 used in this study is able to enrich for hematopoietic repopulating cells.
BACKGROUND: The 5-HT1 agonist sumatriptan, used in the treatment of migraine, can cause chest pain. AIM: To investigate the effect of a therapeutic dose of sumatriptan (6 mg s.c.) on oesophageal motility. METHODS: In 16 normal healthy subjects aged 19-32 years (9 males), the manometric response of the lower oesophageal sphincter (sleeve sensor), oesophageal body (four sites), stomach and pharynx (to register swallows) to 5 mL water swallows was assessed before and after a subcutaneous injection of either sumatriptan (6 mg) or saline control. Symptoms and ECGs were also monitored. RESULTS: Sumatriptan 6 mg s.c. altered oesophageal motility in all subjects. This was reflected by a significant increase in the amplitude of oesophageal body contractions (change from pre- to 1 h post-injection: sumatriptan 9.9 (2.8, 17.1) mmHg vs. placebo -0.8 (-4.2, 2.6) mmHg, difference 10.8 (4.4, 17.1) mmHg; P=0.003) and a transient increase in lower oesophageal sphincter pressure (change from pre- to 5 min post-injection: sumatriptan 10.9 (5.2, 16.6) mmHg vs. placebo 5.1 (1.8, 8.4) mmHg, difference 5.8 (-0.7, 12.3) mmHg; P=0.08). Sumatriptan had no effect on the velocity of propagation of oesophageal contractions (change from pre- to 1 h post-injection: sumatriptan -0.1 (-0.3, 0.1) cm/s vs. placebo -0.1 (-0.3, 0.0) cm/s, difference 0.1 (-0.1, 0.2) cm/s; P = 0.40). One subject experienced chest symptoms following sumatriptan and, although motility was altered, this did not reach pathological levels. No ECG abnormalities were observed. CONCLUSION: Sumatriptan (6 mg s.c.) significantly alters oesophageal motor function without affecting the ECG. It is therefore possible that sumatriptan-induced chest symptoms may have an oesophageal origin. The evaluation of similar therapeutic agents for migraine on oesophageal function may be justified.
OBJECTIVES: To look at students' support for, and perception of, the effects of awarding a degree with honours. DESIGN: Questionnaires were given to all medical students from those entering year 1 to those graduating, i.e. six cohorts. We performed quantitative and qualitative analyses on the responses. SETTING: University of Manchester. SUBJECTS: Medical students. RESULTS: Of 1618 students, 1290 responded (80%). The majority of students thought that we should have a system to award a degree with honours (968/1290[75%]), but this support was related to a number of variables. When asked to rate their agreement to a series of statements, students from the later years were more likely to disagree that an honours system is a helpful motivator for students to learn (Kruskal-Wallis; P < 0.0001). In contrast, those students with 'points' counting towards an honours degree were more likely to agree that there should be an honours system (chi2[1]=18.7, P < 0.0001). CONCLUSIONS: Most students supported the honours system. However, there was less support from students in later years. The qualitative analysis showed a mixture of views. There was a relationship between the probability of being awarding a degree with honours and support of the system.
OBJECTIVE: This project aimed to evaluate the impact of a home visiting programme that targeted families where the child, for environmental reasons, was at great risk of poor health and developmental outcomes. METHODOLOGY: Women in the immediate postpartum period were recruited to a randomized double-blind controlled trial on the basis of self-reported vulnerability factors and were randomly assigned to receive either a structured programme of nurse home visiting, supported by a social worker and paediatrician (n = 90), or assigned to a comparison group receiving standard community child health services (n = 91). Parenting stress and maternal depression were measured at enrollment and at 6 weeks. Preventive health behaviour, service satisfaction and home environment outcomes were tested at 6 weeks, as were child health outcomes. RESULTS: At six weeks, women receiving the home-based programme had significant reductions in postnatal depression screening scores as well as improvements in their experience of the parental role and improvement in the ability to maintain their own identity. Maternal-infant interactions were more likely to be positive, with significantly higher (better) scores in aspects of the home environment related to optimal development in children, particularly maternal-infant secure attachment. Intervention group mothers were significantly more satisfied with the community child health service. CONCLUSIONS: This form of intervention for families is effective in promoting secure maternal-infant attachment, preventing maternal mood disorder and is welcomed by the families receiving it. These findings may predict long-term benefits for the healthy development of children otherwise at risk of a range of poor health and development outcomes.
The neurobiological mechanisms of opiate addictive behaviour in humans are unknown. A proposed model of addiction implicates ascending brainstem neuromodulatory systems, particularly dopamine. Using functional neuroimaging, we assessed the neural response to heroin and heroin-related cues in established opiate addicts. We show that the effect of both heroin and heroin-related visual cues are maximally expressed in the sites of origin of ascending midbrain neuromodulatory systems. These context-specific midbrain activations predict responses to salient visual cues in cortical and subcortical regions implicated in reward-related behaviour. These findings implicate common neurobiological processes underlying drug and drug-cue-related effects.
With the increase in the number of nurses wishing to upgrade their professional qualification to diploma or degree level, there has been a corresponding increase in the number of research modules purchased by education purchasing consortia. One approach to deal with this increase in the number of students, and also to enable students to study at their own pace and in a location convenient to them, is to develop open learning materials. The data presentation and analysis session for the diploma level research module delivered by the Institute of Health Studies at the University of Plymouth has recently been designed using text based material. An opportunity to evaluate this material has arisen during the author's participation in a teaching and learning in higher education course. Twelve out of 25 post-registration students undertaking the diploma level module agreed to take part in the study; six were randomly allocated to the self-study group, and six to the taught session. Information was also collected from the students who did not wish to take part (n = 11). A questionnaire was designed to evaluate knowledge, attitudes to presentation of the material and the method of teaching. Results revealed few differences between the two groups in terms of knowledge and attitudes to presentation of the material and the method of teaching. Of note is that there was an increase in knowledge scores between pre- and post-session assessments for more of the taught session group than the others; and the overall rating was higher for the teaching method than for the self-study material. Reasons given by the 11 who did not wish to take part in the study all related to a preference for a taught session. The implications of these findings are discussed in the context of the limitations of the study, and the development of teaching material in general.
BACKGROUND: The aim of the study was to determine the effect of deprivation on variations in statin prescribing in Nottingham general practices. Deprivation is used as a measure of population cardiovascular morbidity and need for statin treatment. The setting was all 118 general practices in contract with Nottingham Health Authority. METHODS: A cross-sectional study was undertaken. Statin prescribing in general practice during 1996 was related to indices of practice deprivation based on enumeration district (ED) level data from the 1991 Census. The relationship between statin prescribing per 1000 patients aged 35-69 and practice deprivation (measured both as Townsend score and as Jarman UPA(8) score) with additional adjustment for practice characteristics (number of partners, training status, total list size, fundholding status) cardiovascular prescribing costs net of lipid prescribing and hospital activity (total and medical admissions and new general practitioner total and medical out-patient referrals) for each practice. RESULTS: The prescription of statins during 1996 varied between nil and 14.1 'statin-years' of prescribing per 1000 patients aged 35-69. There was a significant inverse relationship between the rate of statin prescribing and the level of deprivation of that practice (p < 0.0001). Deprivation, as measured by Townsend index, accounted for 13 per cent of the total variability in statin prescribing, which rose to 19 per cent after adjustment. The prescribing of other lipid lowering agents of the fibrate class was positively associated with statin prescribing (p=0.001) and this association persisted after adjusting for deprivation. None of the other practice characteristics were found to be significantly associated with rates of statin prescribing. CONCLUSIONS: General practices with high deprivation indices serve more deprived populations with a higher prevalence of cardiovascular disease, and may be assumed to have a greater need for statins. Despite this, practices with higher deprivation indices prescribed fewer statins to their patients than less deprived practices. It was not possible to identify whether the more deprived general practices had successfully identified at risk individuals but it is likely that special efforts are needed to increase the uptake of effective health care in their patients.
BACKGROUND: The relationship between Helicobacter pylori and autoimmune (type A) gastritis is unclear. Infections may trigger autoimmune phenomena but the underlying mechanisms are unknown. AIM: To determine the relationships between H. pylori infection and gastric parietal cell antibodies (PCA), and PCA and heat shock protein (HSP) antibody. METHODS: Fifty-five serum samples positive for PCA, 22 males and 33 females (median age 61 years, range 29-108 years) were compared with 60 control samples negative for PCA, 24 males and 36 females (median age, 48 years, range 11-91 years). H. pylori infection and HSP65K antibodies were determined by enzyme-linked immunosorbent assay. CagA and VacA status were determined by Western blotting. RESULTS: The prevalence of H. pylori was higher in PCA-positives than controls, 29/55 [53%, 95% confidence interval (CI) 39-66%] versus 13/60 (22%, 95% CI 12-34); P= 0.0009. Age was not a confounding factor. Odds ratio for PCA seropositivity if H. pylori-positive was 4.0 (1.79-9.07), P= 0.003. There was an interaction between age and H. pylori, particularly in younger patients. CagA strains were less common in PCA-positives than controls, 10/29 (35%, 95% CI 19-54) versus 9/13 (69%, 39-91), P< 0.05. HSP65K antibodies were elevated in H. pylori infection but to a similar degree for both PCA-positives and controls. CONCLUSION: H. pylori, particularly CagA-negative strains, are associated with autoimmune gastritis and may be implicated in the pathogenesis of autoimmune (type A) gastritis, particularly in younger persons.
Using a unique method we present accurate quantitative measurements of the Ostwald ripening of an emulsion system. Time-resolved small-angle neutron scattering monitors the time evolution of the average radius and number density of the emulsion drops. The results qualitatively agree with the current theory of Ostwald ripening but there is a quantitative, experimentally significant, discrepancy of a factor of 1.7. We argue that these accurate experiments, performed on a well characterized system, provide a most useful basis for testing further refinements of the theory.
A series of consultations between patients treated surgically for colorectal cancer and their hospital consultants were examined to establish the main focus of the consultation at various stages in the post-surgical period. The results showed that follow-up consultations were predominantly doctor driven. Patients interviewed less than 12 months since the time of surgery (short-term group) were more likely to receive a longer consultation with a significantly higher number of verbal interactions (questions, responses) than patients more than 12 months since surgery at the time of interview (long-term group). Furthermore, patients in the short-term group played a greater participatory role within consultations than patients in the long-term group. The predominant focus throughout all consultations was biomedical, with little attention afforded to patients' expressions of post-operative anxiety. At present, it appears that out-patient consultations play a minimal role in either detecting or addressing psychosocial morbidity amongst colorectal cancer patients in the post-surgical period.