Search PubMed⌕ Search

Biomedical subjects

A J Mitchell

Publications and source records attributed to A J Mitchell.

At least 19 recordsLinked to original sources
PubMed2006

Conventional and experimental treatment of cerebral malaria.

The most severe complication of Plasmodium falciparum infection is cerebral malaria (CM). Cerebral malaria implies the presence of neurological features, especially impaired consciousness. The treatment of CM is limited to: (i) a few conventional anti-malarial drugs (quinine or artemisinins), (ii) adjunctive treatments (initial stabilisation, blood exchange transfusion, osmotic diuretics and correction of hypoglycaemia, acidosis and hypovolaemia) and (iii) immunomodulation. There are clear procedures concerning treatment of CM, which include the use of the anti-plasmodial drugs. Adjunctive treatments are permissible but there is no single official guideline and immune intervention is a possibility currently being examined in rodent models only. The suggested immunomodulation approach is based on the strong likelihood that CM is the result of an immunopathological process. P. falciparum initiates the multifactorial chain of events leading to lethal CM and, after a certain stage, it is impossible to stop the progression even by using anti-malarial drugs. We present evidence that CM is a result of a dysregulated immune response. Therefore, it might be prevented by early modulation of discrete factors that participate in this process. In experimental systems, some immunomodulators delay or prevent CM without affecting the parasitaemia. Therefore, in the future the ultimate treatment of CM may be a combination of an anti-malarial and an immunomodulator. However, the overall effect of an immunomodulator would need to be carefully examined in view of concomitant infections, especially in malaria endemic areas.

Animals↗
PubMed2006

Self harm and attempted suicide in adults: 10 practical questions and answers for emergency department staff.

Self harm is a complex behaviour that can be best thought of as a maladaptive response to acute and chronic stress, often but not exclusively linked with thoughts of dying. Patients presenting with self harm usually have current psychosocial difficulties, are likely to be suffering from mental health problems, and are at significant risk of further self harm and suicide. Recent guidelines suggest that all self harm attendees should receive an initial risk assessment at triage in the emergency department. A more detailed mental health assessment and an assessment of psychological and social needs should then be performed by trained staff, ideally specialist mental professionals experienced in this area. Risk of subsequent suicide is particularly high in those with high unresolved suicidal intent, depressive disorder, chronic alcohol and drug misuse, social isolation, and current physical illness. Patients with one or more of these risk factors should be offered enhanced care that may include inpatient or outpatient follow up care, a list of local support resources, and, where possible, self help material. Frequent repeaters, those with alcohol and substance use problems, those with physical or mental illness, and those who are isolated also require input from specialist mental health professionals. It is also recommended that adolescents and elderly people warrant a mandatory specialist assessment.

Adult↗
PubMed2005

Phagocyte-derived reactive oxygen species do not influence the progression of murine blood-stage malaria infections.

Phagocyte-derived reactive oxygen species have been implicated in the clearance of malaria infections. We investigated the progression of five different strains of murine malaria in gp91(phox-/-) mice, which lack a functional NADPH oxidase and thus the ability to produce phagocyte-derived reactive oxygen species. We found that the absence of functional NADPH oxidase in the gene knockout mice had no effect on the parasitemia or total parasite burden in mice infected with either resolving (Plasmodium yoelii and Plasmodium chabaudi K562) or fatal (Plasmodium berghei ANKA, Plasmodium berghei K173 and Plasmodium vinckei vinckei) strains of malaria. This lack of effect was apparent in both primary and secondary infections with P. yoelii and P. chabaudi. There was also no difference in the presentation of clinical or pathological signs between the gp91(phox-/-) or wild-type strains of mice infected with malaria. Progression of P. berghei ANKA and P. berghei K173 infections was unchanged in glutathione peroxidase-1 gene knockout mice compared to their wild-type counterparts. The rates of parasitemia progression in gp91(phox-/-) mice and wild-type mice were not significantly different when they were treated with l-N(G)-methylarginine, an inhibitor of nitric oxide synthase. These results suggest that phagocyte-derived reactive oxygen species are not crucial for the clearance of malaria parasites, at least in murine models.

Animals↗
PubMed2005

Functional symptoms in neurology: questions and answers.

Between 10 and 30% of patients seen by neurologists have symptoms for which there is no current pathophysiological explanation. The objective of this review is to answer questions many neurologists have about disorders characterised by unexplained symptoms (functional disorders) by conducting a multidisciplinary review based on published reports and clinical experience. Current concepts explain functional symptoms as resulting from auto-suggestion, innate coping styles, disorders of volition or attention. Predisposing, precipitating, and perpetuating aetiological factors can be identified and contribute to a therapeutic formulation. The sympathetic communication of the diagnosis by the neurologist is important and all patients should be screened for psychiatric or psychological symptoms because up to two thirds have symptomatic psychiatric comorbidity. Treatment programmes are likely to be most successful if there is close collaboration between neurologists, (liaison) psychiatrists, psychologists, and general practitioners. Long term, symptoms persist in over 50% of patients and many patients remain dependent on financial help from the government. Neurologists can acquire the skills needed to engage patients in psychological treatment but would benefit from closer working relationships with liaison psychiatry or psychology.

Humans↗
PubMed2004

A systematic approach to analyse health-related quality of life in multiple sclerosis: the GEDMA study.

OBJECTIVE: To describe a holistic and comprehensive approach to the assessment of sufferer's perceptions of health-related quality of life (HRQoL) in a cohort of multiple sclerosis (MS) patients. METHODS: The GEDMA (Grupo de Enfermedades Desmielinizantes de Madrid, in Spanish) study is an ongoing longitudinal survey using quantitative and qualitative methodologies. The baseline cohort consisted of a large sample of MS patients recruited from 13 hospitals in Madrid, Spain. Using a standardized protocol we collected data concerning the sociodemographic and health status characteristics of patients, as well as implementing a modified Spanish version of the Functional Assessment of Multiple Sclerosis quality of life instrument Primary caregivers were interviewed using a specific protocol combined with the Zarit Burden Interview. RESULTS: The index cohort comprised 371 MS patients (68.7% female) of mean age 38.9+/-0.9 years. Age, sex and clinical form distribution were similar to other MS population-based surveys. There were 258 (69.5%) relapsing-remitting (RR) MS patients and 113 (30.5%) progressive MS patients. More than one-third of the married patients with progressive MS and almost a quarter of the RRMS patients separated or divorced following a diagnosis of MS; 71.3% of the progressive MS patients as well as 65.8% of the RRMS patients were unemployed as a consequence of the disease. Qualitative analysis showed that friendship and family relationships and occupational status were the most significant dimensions influenced by MS. On the other hand, the speech analysis of primary caregivers showed that emotional burden was related to patients' physical disability. Furthermore, primary caregivers described the influence of MS on their own occupational status, their nonacceptance of the disease, a perception of a lack of support by other members of the family as well as a 'selfish and intransigent' attitude of the patients themselves. CONCLUSIONS: The analysis of the GEDMA cohort provides valuable information that helps clarify the impact of MS on patients' HRQoL.

Adult↗
PubMed2004

CBT for psychosis.

Explore the source record for details and available documents.

Cognitive Behavioral Therapy↗
PubMed2002

The biological activity of serum IgE changes over the course of a primary response.

Mast-cell degranulation is triggered by the bridging of Fc receptor-bound antigen-specific immunoglobulin IgE on the cell surface. In vitro experiments suggest that antibody affinity and nonspecific IgE may affect the mast-cell function, however, their importance in vivo is unclear. Investigations of the effects of these parameters on mast-cell sensitization were therefore carried out in a rat immunization model in which the IgE response is transient and peaks on days 10-15. Between these two timepoints, significant changes in the level of specific IgE were not observed, but the avidity of specific IgE increased (P < 0.05). Total serum IgE peaked on day 10 and slowly declined, with the relative proportion of specific to total IgE increasing from day 10-15 (P < 0.05). Despite similar levels of antigen-specific IgE, increasing avidity and an increased proportion of specific IgE between days 10 and 15, the biological activity of IgE in the serum peaks on day 10 and declines rapidly, dropping around seven-fold by day 15 (P < 0.001). Mechanisms that could explain this finding, such as differential expression of IgE isoforms and changes in the fine specificity of the IgE response, are discussed.

Animals↗
PubMed2002

Double contrast barium enema sensitivity: a comparison of studies by radiographers and radiologists.

PURPOSE: A retrospective study of histologically proven cases of colorectal cancer (CRC) was performed to assess whether the sensitivity of the radiographer-performed double contrast barium enema (DCBE) differed from that of the radiologist-performed study. MATERIALS AND METHODS: Histologically proven cases of CRC were reviewed over a 3-year period to ascertain whether: the diagnosis had been made by DCBE in the 3 years before histological diagnosis; the lesion had been correctly diagnosed; the examination had been performed by a radiologist or radiographer. RESULTS: In the 3-year period there were 478 cases with histologically proven CRC. Of these, 239 (50%) had undergone DCBE as the initial radiological investigation of the colon. Sixty-four examinations had been performed by radiographers. A correct diagnosis was made in 58 cases (90.6%), the report was equivocal in one case (1.6%), there were four false-negatives (6.25%), and one case was abandoned (1.6%). One hundred and seventy-five examinations were performed by radiologists. A correct diagnosis was made in 157 cases (89.7%), the report was equivocal in one case (0.6%), there were 16 false-negatives (9.1%), and one case was abandoned (0.6%). CONCLUSION: A sensitivity of 90.6% for radiographer-performed studies compared favourably with 89.7% for radiologist-performed studies and supports the practice of radiographers undertaking barium enemas.

Barium Sulfate↗
PubMed2002

The quality of psychotropic drug prescribing in patients in psychiatric units for the elderly.

The quality of written prescriptions has not been examined in a psychiatric setting. The aim of this study was to examine the quality of drug prescribing by medical staff for elderly patients hospitalized with dementia in comparison with the quality of prescribing for elderly patients hospitalized for functional psychiatric illness (depression, anxiety and psychosis). We studied a cohort of 112 elderly psychiatric inpatients in two hospitals over a seven-year period. A standardized assessment sheet was used to assess 320 prescriptions of psychotropic drugs, using medical notes and drug charts. Patients with dementia and functional illness were defined by ICD-9 or ICD-10 criteria. Severity of illness was measured by the presence or absence of symptoms in six discrete symptom clusters. Two raters examined prescription quality. Twenty percent of prescriptions for patients with dementia were illegible, significantly higher than in functional illness. In both groups, among prescriptions of regular medication, one third contained missing information on either, dose, intended frequency, or, indications for use. Among prescriptions for as-required medication, two-thirds of prescriptions contained this missing information. Prescriptions were legible and free of all errors in only 20 of 112 cases (18%). Quality of as-required medication prescribing was inferior to the prescription of regular medication, particularly for dementia patients. In addition, prescribing for patients with dementia carried significantly more errors in notation of dose than prescribing for patients with functional illness. We conclude that errors are common in prescribing for elderly psychiatric patients, particularly for as-required medication and for patients with dementia.

Aged↗
PubMed2001

Valency or wählency: is the epitope diversity of the B-cell response regulated or chemically determined?

For almost a century, the humoral immune response has been monitored principally by the measurement of antibody concentrations, although antibody affinity and isotype have also long been acknowledged as critical to their biological activity. In this report, it is argued that these measures alone may provide a poor measure of the activity of serum antibodies. A B-cell response that is directed against multiple epitopes on a protein can form immune complexes bearing multiple antibody molecules. This is essential for the efficient initiation of processes such as the complement cascade and the activation of leucocytes via Fc receptors. These processes can be dramatically enhanced when B cells target a greater number of epitopes on any antigen. Evidence that the epitope diversity of an immune response may vary between individuals, and that it may vary in an individual over time, is reviewed. This variability is likely to be influenced by a number of host-specific factors in addition to antigen chemistry. The appropriateness of the chemically deterministic term 'antigen valency' to describe the number of epitopes recognized by an individual's B-cell response is discussed, and the term 'wählency' to emphasize the situational nature of B-cell epitopes is introduced.

Animals↗
PubMed2000

Requirement for DARPP-32 in progesterone-facilitated sexual receptivity in female rats and mice.

DARPP-32, a dopamine- and adenosine 3',5'-monophosphate (cAMP)-regulated phosphoprotein (32 kilodaltons in size), is an obligate intermediate in progesterone (P)-facilitated sexual receptivity in female rats and mice. The facilitative effect of P on sexual receptivity in female rats was blocked by antisense oligonucleotides to DARPP-32. Homozygous mice carrying a null mutation for the DARPP-32 gene exhibited minimal levels of P-facilitated sexual receptivity when compared to their wild-type littermates. P significantly increased hypothalamic cAMP levels and cAMP-dependent protein kinase activity. These increases were not inhibited by a D1 subclass dopamine receptor antagonist. P also enhanced phosphorylation of DARPP-32 on threonine 34 in the hypothalamus of mice. DARPP-32 activation is thus an obligatory step in progestin receptor regulation of sexual receptivity in rats and mice.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

The role of corticotropin releasing factor in depressive illness: a critical review.

Corticotropin-releasing factor (CRF) is the principal neuropeptide involved in regulating the stress response. When centrally administered to animals it produces somatic changes analogous to those seen in both depression and anxiety. In humans, it is capable of reproducing the hormonal changes which are characteristically seen in depressed patients. A literature search using Medline, Embase Psychiatry, PsycLIT and BIDS from 1996-1997 revealed 25 studies that have examined CRF concentrations in patients with affective disorder. The methodology of these studies varies and they can be criticised, in particular, for failing to consider the stress response of the lumbar puncture. Recently, post-mortem immunocytochemical techniques have been employed to help clarify the nature of these abnormalities in depression. On balance, evidence from CSF sampling, post-mortem findings and dynamic endocrine studies suggests that both hypothalamic and extra-hypothalamic concentrations of CRF are moderately elevated in a proportion of currently antidepressant treatment, high CRF concentrations tend to normalise. The causes of increased CRF output in depression are also unknown but may involve an integration of remote vulnerability factors and recent stressors perhaps mediated through impaired function of glucocorticoid receptors. Ultimately, the careful manipulation of CRF may hold therapeutic promise for sufferers of mood disorders.

Animals↗
PubMed1997

The effects of agar concentration on the growth and morphology of submerged colonies of motile and non-motile bacteria.

The growth and morphology of submerged bacterial colonies was investigated. Five separate colonial forms were recognized depending both on species and on agar concentration. These were (i) branched, dendritic structures seen only with Bacillus cereus; (ii) lenticular colonies for all other species at high agar concentrations; (iii) small lobed to spherical colonies for non-motile organisms at low agar concentrations; (iv) and (v) large diffuse spherical colonies which can be further subdivided into 'snowball' or 'wispy' types for motile bacteria growing at agar concentrations below about 0.65% w/v. Viable count determinations suggested that agar concentration had little effect in the early stages of growth but that motile cells at low agar concentrations achieved higher cell numbers than did those in concentrations greater than 0.65% w/v. Transmission electron microscopy indicated that bacteria in lenticular colonies were tightly packed within lens-shaped splits in the agar whilst at low agar concentrations motile cells were well separated and appeared to move through the agar matrix.

Agar↗
PubMed1996

Depression-related cognitive impairment: possibilities for its pharmacological treatment.

Depression-related cognitive impairment (DRCI) is a condition which despite its initial treatment response, shows a progressive deterioration. No consistent therapeutic strategies have been proposed to combat this condition. This may be due to a reluctance to treat the cognitively impaired, a failure to recognise the deleterious prognosis or a poor understanding of the likely pathogenesis. Increasing evidence implicates the hypothalamo-pituitary-adrenal (HPA) axis as a key neurobiological determinant of the presentation and course of depression-induced cognitive decline. By utilising agents which control central glucocorticoid hyperactivity over a sustained period, whilst avoiding those agents which may compromise cognitive abilities, there exists a pharmacological strategy which may minimise the morbidity of cognitive impairment related to depressive illness.

Aged↗
PubMed1995

Cloning of a pea cDNA encoding a polypeptide of the light-harvesting complex associated with photosystem I using a monoclonal antibody.

A monoclonal antibody (MAb UB42) is described that binds to thylakoids in pea chloroplasts, as shown by EM-immunogold labelling. The antibody recognised proteins of ca. 23-29 kDa in western blots of a pea leaf homogenate. A cDNA library was prepared from pea epidermal cells in the vector lambda ZAP II, and immunoscreening of the library with UB42 led to the isolation of a clone, pUB42. This was sequenced and had an open reading frame of 269 codons encoding a predicted polypeptide of 28.9 kDa. The sequence showed extensive homology with three closely related polypeptides belonging to a family of chlorophyll a/b-binding proteins from the light harvesting complex of photosystem I (LHCI). Collectively, the results suggest that MAb UB42 recognises an epitope on the type II chlorophyll a/b-binding protein from LHCI and that clone pUB42 encodes this protein.

Amino Acid Sequence↗