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Biomedical subjects

J Robinson

Publications and source records attributed to J Robinson.

At least 271 records · Page 15Linked to original sources

Hyperlipidaemia does not impair vascular endothelial function in glycogen storage disease type 1a.

Patients with glycogen storage disease type 1 (GSD-1) often have marked hyperlipidaemia with abnormal lipoprotein profiles. This metabolic abnormality improves, but is not fully corrected, with dietary therapy and therefore these patients may be at high risk for the development of atherosclerosis. Endothelial dysfunction is an early event in atherogenesis and can be detected in children and young adults at high risk. We studied endothelial function, using a non-invasive ultrasonographic method, in the brachial arteries of 6 adult GSD-1a patients (aged 23-33 years) with mean cholesterol of 7.9 mmol/l (range 4.7 to 14.6) and mean triglycerides of 9.1 mmol/l (range 4.1 to 21.3), and 12 age- and sex-matched normolipidaemic controls. Flow-mediated (endothelium-dependent) dilation was similar in patients and controls (8.2% vs. 10.5%; P = 0.20). Although the patient numbers are small, these results are consistent with the surprising lack of clinically evident atherosclerosis in GSD-1. The reasons these patients appear less susceptible to the damaging arterial effects of hyperlipidaemia are unknown. These results may have implications for others with secondary hyperlipidaemias.

Adult↗

Dynamics of the CA3 pyramidal neuron autoassociative memory network in the hippocampus.

A theory for the dynamics of sparse associative memory has been applied to the CA3 pyramidal recurrent network in the hippocampus. The CA3 region is modelled as a network of pyramidal neurons randomly connected through their recurrent collaterals. Both the elliptical spread of the axonal systems and the exponential decrease in connectivity with distance are taken into account in estimating the connection probabilities. Pyramidal neurons also receive connections from inhibitory interneurons which occur in large numbers throughout the network; these in turn receive inputs from other inhibitory interneurons and from pyramidal neurons. These inhibitory neurons are modelled as rapidly acting linear devices which produce outputs proportional to their inputs; they perform an important regulatory function in the setting of the membrane potentials of the pyramidal neurons. The probability of a neuron firing in a stored memory, which determines the average number of neurons active when a memory is recalled, can be set at will. Memories are stored at the recurrent collateral synapses using a two-valued Hebbian. Allowance is made in the theory both for the spatial correlations between the learned strengths of the recurrent collateral synapses and temporal correlations between the state of the network and these synaptic strengths. The recall of a memory begins with the firing of a set of CA3 pyramidal neurons that overlap with the memory to be recalled as well as the firing of a set of pyramidal neurons not in the memory to be recalled; the firing of both sets of neurons is probably induced by synapses formed on CA3 neurons by perforant pathway axons. The firing of different sets of pyramidal neurons then evolves by discrete synchronous steps. The CA3 recurrent network is shown to retrieve memories under specific conditions of the setting of the membrane potential of the pyramidal neurons by inhibitory interneurons. The adjustable parameters in the theory have been assigned values in accord with the known physiology of the CA3 region. Certain levels of overlap between the input and the memory to be retrieved must also be satisfied for almost complete retrieval. The number of memories which can be stored and retrieved without degradation is primarily a function of the number of active neurons when a memory is recalled and the degree of connectivity in the network. The inhomogeneity in the connectivity of the pyramidal cells improves both capacity and overlap of the final state with the memory.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Project 2000 and the replacement of the traditional student workforce.

This paper reports on part of a 4-year study monitoring the implementation of Project 2000 in one health authority. Its focus is on the consequences for the nursing service of replacing traditional, pre-Project 2000 students with permanent staff. It is argued that the Department of Health, who have been responsible for funding the replacement programme, have underestimated the numbers of permanent staff required to replace the traditional student workforce, and that the Project 2000 replacement exercise has contributed to a deterioration in staffing levels and skill mix.

Delivery of Health Care↗

Oral hairy leukoplakia in nonimmunosuppressed patients. Report of four cases.

Hairy leukoplakia was first described in association with HIV infection. Today hairy leukoplakia has come to represent a sign of immunosuppression and not just of HIV infection. Although molecular mechanisms have not been fully elucidated, Epstein-Barr virus appears to play a significant role in its etiopathogenesis. We present four cases that illustrate that HL may be seen in non-HIV and nonimmunocompromised patients. The use of high potency topical steroids for the treatment of oral vesiculoerosive diseases seems to have been a contributing factor in two of these cases.

Administration, Topical↗

Structural characterization of broadly neutralizing human monoclonal antibodies against the CD4 binding site of HIV-1 gp120.

The human monoclonal antibodies (mAbs) 15e and 21h are derived from HIV-1-infected individuals. They block CD4 binding, recognize conformation-dependent discontinuous epitopes on gp120 and neutralize a broad range of laboratory strains and primary isolates of HIV-1. To determine if a structural basis for neutralization could be identified, analysis of these CD4-binding site anti-gp120 human mAbs was performed, common features and differences were identified and a comparison was made with F105, a previously reported CD4-binding site anti-gp120 human mAb. The 15e and 21h mAb heavy chains are derived from different V region genes, i.e. V2-1 and VDP-35, which are members of the VHIV and VHIII families, respectively. Analysis of the genes encoding the heavy chain complementarity determining region (CDR) 3 revealed that both mAbs show a long DH segment of similar size that could arise from D-D fusions of the dxp1/dlr1 and daudi/d22-12 germline DH genes along with use of the JH6 and JH5 germline segments. Similarly, the 15e and 21h light chains are derived from different V region genes, i.e. Hum01/012 and Hum1v318, that are members of the V kappa I and V lambda IIIa gene families, respectively. These V genes are rearranged with J kappa 1 and J lambda 2 germline genes. For both mAbs, the pattern of replacement mutations in the V region genes of the heavy and light chains is consistent with a process of somatic mutation and antigen-driven clonal selection. By comparing the CDRs of 15e, 21h and F105, eight positions in the rearranged heavy chains and two positions in the rearranged light chains were found to have identical amino acids. These studies suggest that there is no absolute restriction in the use of V region germline genes and form the foundation for understanding the humoral immune response to the CD4-binding site of gp120.

Amino Acid Sequence↗

Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women.

OBJECTIVES: This study assessed whether aging is associated with progressive endothelial dysfunction, whether the pattern of any age-related decline in vascular health is different in men and women and whether any gender difference is consistent with known changes in hormonal status. BACKGROUND: Coronary and cerebrovascular disease are much less common in young and middle-aged women compared with men, although the gender difference in death from atherosclerosis is less marked after the menopause. Endothelial dysfunction is an early event in atherogenesis and is important in dynamic plaque stenosis in later life. The effect of aging on endothelial function in men and women, however, is not well known. METHODS: We used high resolution ultrasound to study endothelium-dependent and endothelium-independent vascular responses. Brachial artery physiology was investigated in 238 subjects (103 men, 135 women; mean [+/- SD] age 38 +/- 17 years, range 15 to 72) with no known risk factors for atherosclerosis. The responses to reactive hyperemia (flow-mediated dilation, which is endothelium dependent) and to glyceryl trinitrate (an endothelium-independent dilator) were assessed for all the subjects and then for men and women separately. RESULTS: On multivariate analysis for the whole group, reduced flow-mediated dilation was related to older age (r = -0.34, p < 0.0001). In men, flow-mediated dilation was preserved in subjects aged < or = 40 years but declined thereafter at 0.21%/year. In women, flow-mediated dilation was stable until the early 50s, after which it declined at 0.49%/year (p = 0.002 compared with men). In contrast, there was no significant change in the glyceryl trinitrate response with aging in either gender. CONCLUSIONS: Aging is associated with progressive endothelial dysfunction in normal humans, and this appears to occur earlier in men than in women. In women, however, a steep decline commences at around the time of the menopause. This is consistent with a protective effect of estrogens on the arterial wall.

Adolescent↗

Primary cultures of human bone-derived cells produce parathyroid hormone-related protein: a study of 40 patients of varying age and pathology.

Parathyroid hormone-related protein (PTHrP), a mediator of hypercalcemia of malignancy, has been detected in many tumours and in some normal foetal and adult tissues. PTHrP has potent effects on bone turnover in vivo and in vitro. In this study we cultured cells derived from explants of bone obtained from 40 subjects (age range 2-88 years). Immunoreactive PTHrP (iPTHrP) was detected by immunoradiometric assay (IRMA) in conditioned medium from 25 of 40 cultures of bone-derived cells. PTHrP mRNA was detected in bone-derived cells by reverse transcriptase-linked polymerase chain reaction (RT-PCR). The identity of PCR products was confirmed by Southern blotting. Local production of PTHrP in vivo may be important in the regulation of bone growth and remodelling.

Adolescent↗

Midwifery profile.

Explore the source record for details and available documents.

Career Choice↗

Emotional availability in mother-twin dyads: effects on the organization of relationships.

The term "emotional availability" has evolved primarily in therapeutic contexts where it refers to the sensitive engagement of the therapist in the patient's narrative of life experiences and openness to the patient's emotional expressions (Emde 1980). In the therapeutic situation, emotional availability refers to the quality of the therapist in supporting the growth or development of the patient. It is anticipated that the outcome of the therapeutic experience will include an enhanced capacity for reciprocal emotional availability with others.

Child, Preschool↗

Influence of deletions in N or C terminus of HIV-1 glycoprotein 120 on binding of infectivity-enhancing antibody.

Human monoclonal antibody 2.3a was previously shown to enhance human immunodeficiency virus type 1 (HIV-1) infection in vitro. This enhancing antibody recognizes a conserved epitope of envelope glycoprotein gp120. We report here that binding of the 2.3a antibody to gp120 is significantly affected by deletions of certain N- or C-terminal residues of gp120. However, not all such deletions affect the epitope recognized by a broadly neutralizing human monoclonal antibody, 1.5e. These findings suggest the feasibility of designing a gp120 antigen that is free of 2.3a epitope while retaining the conformation of the 1.5e epitope.

Amino Acid Sequence↗

Zopiclone as a preoperative night hypnotic: a double-blind comparison with temazepam and placebo.

We have examined the hypnotic effects of zopiclone 7.5 mg and temazepam 20 mg compared with placebo in a double-blind, randomized, clinical study of 60 patients on the night before operation. Evaluation was both subjective (visual analogue scales and a sleep questionnaire), to measure the quality of sleep, and objective (critical flicker fusion, object recall and paired associates tasks), to measure residual impairment. We found that zopiclone was an effective single-dose hypnotic with similar residual effects to the benzodiazepine and it may therefore provide a suitable alternative to benzodiazepines.

Adolescent↗

Magnetic resonance imaging and transvaginal ultrasound of the uterus prior to embryo transfer.

This study was designed to investigate the role of magnetic resonance (MR) imaging in predicting the outcome of in-vitro fertilization (IVF)/embryo transfer treatment by seeking differences in receptive compared to unreceptive endometria. Women about to undergo embryo transfer were submitted to both vaginal ultrasound and MR imaging. Measurements were obtained of the thickness, cross-sectional area and volume of uterine layers and of the MR signal intensity ratios between layers. Measurements were compared with the occurrence of subsequent successful implantation. Although there was no association with either the quantity or the relative signal intensity of the endometrium, an interdependence was demonstrated between both the endometrium/myometrium and myometrium/junctional zone signal intensity ratios and subsequent successful implantation (P < 0.037 and < 0.004 respectively). It is concluded that MR imaging may provide unique information which may help in predicting the outcome of IVF/embryo transfer treatment and in understanding implantation. Significant differences were seen in the relative MR signal intensities of the myometrium.

Adult↗

Fundholding in Northern Region: practice managers' views.

Describes the views of practice managers in 30 fundholding practices in the Northern Region concerning their role in the scheme. A self-completion questionnaire was mailed to practice managers and general practitioners containing questions designed to elicit their views about changes in relationships inside and outside the practice; their level of involvement in various aspects of fundholding; and the costs and benefits of the scheme. A total of 30 first-, second-, and third-wave fundholding practices in the Northern Region, June 1993 were involved. Replies were received from 22 practice managers (73 per cent) and 83 general practitioners (49 per cent). Concludes that although fundholding has increased the nature and volume of the workload of practice managers, these changes do not appear to be causing any tensions between managers and clinicians. At the moment fundholding extends the support role of practice managers and does not alter existing authority relations in practices.

Attitude of Health Personnel↗

Change in process: bringing about change in health care through action research.

A 2-year action-research project aiming to facilitate the management of change was carried out in a district general hospital. Hospital managers and senior ward nurses had very different views concerning the source of challenges and problems within the hospital organization. A case-study of nurses' experience of change at ward level was produced as part of the diagnostic phase of the action research. The results of the case-study indicated that general managers and professionals had different agendas for change but that there is common ground between them.

Hospital Administrators↗

Toxocara canis-induced murine pulmonary inflammation: analysis of cells and proteins in lung tissue and bronchoalveolar lavage fluid.

The pulmonary immuno-inflammatory reaction and its effect on microvascular integrity was studied in Toxocara canis infected BALB/c mice. The investigation aimed to compare changes in lung histology and composition of bronchoalveolar lavage fluid (BALF) caused by T. canis infection with those described to occur in allergic asthma. Groups of (non)-infected mice (1000 ova) were investigated until 90 days post infection (p.i.). Migration of the larvae through the lungs was followed by a rapidly progressing multifocal interstitial and alveolar inflammation. Eosinophils and lymphocytes formed perivascular and partially peribronchial mixed cellular infiltrates. Lymphocytes with plasma cell morphology staining intracellularly for either alpha, epsilon or gamma immunoglobulins were demonstrated. BALF, collected from mice infected with either 250, 500 or 1000 ova was analysed at 14 and 28 days p.i. A dose-related increase in cell numbers and in albumin and IgA concentration was observed. IgE increase was independent of the infective dose. Peak values were measured at 14 days p.i. Albumin increase in lung homogenate was highest at 28 days p.i. 30% of the lymphocytes consisted of T cells carrying Thy-1,2 and L3T4 surface antigens. It is concluded that T. canis-induced pulmonary inflammation affects the permeability of the microvasculature. This is expressed by interstitial oedema and plasma exudation in the airway lumen. Both phenomena occur also in allergic asthma. It is suggested that increased permeability of the microvasculature is mediated by T cells and eosinophils.

Albumins↗