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Biomedical subjects

Brian Brown

Publications and source records attributed to Brian Brown.

30 records · Page 2Linked to original sources

The autonomic control of accommodation and implications for human myopia development: a review.

Prolonged nearwork has long been associated with myopia development, however, there is no well described linking mechanism. One theory suggests that if accommodation accuracy during nearwork is not maintained, the defocused retinal image leads to myopia development. Here we review the findings of research aimed at determining whether the autonomic inputs to the ciliary smooth muscle are involved in this type of environmental myopia. We examine whether an autonomic imbalance could be a precursor to axial elongation and the resulting myopia. Accommodation responses, such as tonic accommodation and nearwork-induced accommodative adaptation, as a function of refractive error, are described in relation to an autonomic imbalance model. The collective results of this research point to anomalous accommodation responses, possibly as a result of underlying anomalous autonomic input to the ciliary muscle, being involved in myopia development and progression.

Accommodation, Ocular↗

AC/A ratios in myopic and emmetropic Hong Kong children and the effect of timolol.

PURPOSE: Caucasian children with myopia have elevated response accommodative vergence to accommodation (AC/A) ratios. The purpose of this study was twofold: to determine if response AC/A ratios vary with refractive error and with myopic progression rate in Hong Kong Chinese children, and to determine the effect of beta-adrenergic antagonism with topical timolol application on AC/A ratios. METHODS: Thirty children aged eight to 12 years participated in the study. All refractive errors were corrected with spectacle lenses. Accommodative responses were measured using a Shin-Nippon autorefractor and concurrent changes in vergence were assessed using a vertical prism and a Howell-Dwyer card at three metres and 0.33 metre. Accommodative demand was altered using plus or minus two dioptre lenses and lens- and distance-induced response AC/A ratios were calculated. Measurements were repeated 30 minutes after the instillation of topical timolol maleate (0.5 per cent). RESULTS: AC/A ratios appeared higher in progressing myopic children but the difference was not statistically significant. Timolol application reduced accommodative convergence (AC) in the stable myopes (reduction = -3 +/- 1.14 prism dioptres) but not in the emmetropes (0.69 +/- 0.96 prism dioptres) or progressing myopes (0.16 +/- 0.43 prism dioptres) and this difference between refractive groups was statistically significant (F(2, 27) = 3.766; P = 0.036). However, timolol did not produce a significant change in the accommodative response to positive or negative lenses or response AC/A ratios. CONCLUSIONS: We did not find that AC/A ratios in myopic Chinese children were elevated and therefore, it is unlikely that elevated AC/A ratios are responsible for the high levels of myopia that occur in Hong Kong. The finding that timolol reduced AC in the stable myopes suggests that the autonomic control of accommodative convergence in these children may be different from that in emmetropic children and those with progressing myopia.

Accommodation, Ocular↗

Pepsinogen C expression in intestinal IEC-6 cells.

Pepsinogen C (PGC) is the inactive precursor of pepsin C, which is a member of the aspartic proteinase family of proteolytic enzymes, and is found within the vertebrate stomach. The precursor molecule is synthesised within the gastric epithelial cells and secreted into the gastric lumen where it undergoes an autocatalytic activation under acidic conditions to the proteolytic molecule. However, the synthesis of PGC has also been reported in numerous non-gastric tissues including the prostate gland and the Brunner's gland of the small intestine. The physiological significance of PGC in these tissues is not known and studies are limited by the lack of appropriate in vitro cell models. We report here the use of the rat intestinal cell line, IEC-6, as an in vitro model to study the role of pepsinogen C in the intestine. PGC expression was detected in the IEC-6 cells by RT-PCR and immunocytochemistry, using a PGC specific antibody, localised the protein to cytoplasmic secretory granules. Enzymatic assay confirmed the presence of a functional protein exhibiting pepsin activity. Using semi-quantitative RT-PCR we showed that PGC gene expression was up-regulated by the gastro-intestinal hormones gastrin and secretin, and forskolin which stimulates adenylate cyclase activity. This study demonstrates that the IEC-6 cells provide a unique in vitro model for studying pepsinogen C and its potential role(s) in the small intestine.

Animals↗

Therapeutic factor VIII levels and negligible toxicity in mouse and dog models of hemophilia A following gene therapy with high-capacity adenoviral vectors.

High-capacity adenoviral (HC-Ad) vectors expressing B-domain-deleted human or canine factor VIII from different liver-specific promoters were evaluated for gene therapy of hemophilia A. Intravenous administration of these vectors into hemophilic FVIII-deficient immunodeficient SCID mice (FVIIIKO-SCID) at a dose of 5 x 10(9) infectious units (IU) resulted in efficient hepatic gene delivery and long-term expression of supraphysiologic FVIII levels (exceeding 15 000 mU/mL), correcting the bleeding diathesis. Injection of only 5 x 10(7) IU still resulted in therapeutic FVIII levels. In immunocompetent hemophilic FVIII-deficient mice (FVIIIKO), FVIII expression levels peaked at 75 000 mU/mL but declined thereafter because of neutralizing anti-FVIII antibodies and a cellular immune response. Vector administration did not result in thrombocytopenia, anemia, or elevation of the proinflammatory cytokine interleukin-6 (IL-6) and caused no or only transient elevations in serum transaminases. Following transient in vivo depletion of macrophages before gene transfer, significantly higher and stable FVIII expression levels were observed. Injection of only 5 x 10(6) HC-Ad vectors after macrophage depletion resulted in long-term therapeutic FVIII levels in the FVIIIKO and FVIIIKO-SCID mice. Intravenous injection of an HC-Ad vector into a hemophilia A dog at a dose of 4.3 x 10(9) IU/kg led to transient therapeutic canine FVIII levels that partially corrected whole-blood clotting time. Inhibitory antibodies to canine FVIII could not be detected, and there were no signs of hepatotoxicity or of hematologic abnormalities. These results contribute to a better understanding of the safety and efficacy of HC-Ad vectors and suggest that the therapeutic window of HC-Ad vectors could be improved by minimizing the interaction between HC-Ad vectors and the innate immune system.

Adenoviruses, Human↗

Reluctant empiricists: community mental health nurses and the art of evidence-based praxis.

The National Service Framework for Mental Health (1999) emphasizes the need for a culture of evidence-based practice (EBP) in mental health care. However, there is relatively little research addressing EBP from the perspective of community mental health nurses and we are still unsure of why the uptake of this style of working has been slow. This paper suggests that rather than thinking in terms of 'barriers' to the uptake of EBP, the issue may best be conceptualized as a form of praxis on the part of nurses, as they seek to manage the diversity of ideologies and practices in their working lives. From an interview and focus group study, we identify how practitioners' narrow definition of EBP itself, their formulation of how EBP was at odds with the nurse's professional activity and the organizational constraints within which they work were perceived to inhibit access to information and offer little time and managerial support for information seeking. Those who attempt to further the involvement of community mental health staff in EBP will have to reconceptualize the reasons why staff have yet to incorporate it fully, and acknowledge that this does not occur because staff are simply 'ignorant Luddites', but that this resistance enables them to retain a sense of control over their working lives and retain a focus on work with clients. Future EBP initiatives will have to address these ideological and organizational factors in order for uptake to be accelerated. This may involve changing organizational cultures and work roles and even encouraging activism on the part of the practitioners so as to enable them to learn from each other and educate and change their work environments.

Community Health Nursing↗

Is esophoria a factor in slowing of myopia by progressive lenses?

PURPOSE: Our previous findings suggest that myopia can be slowed by wearing progressive lenses, and one possible mechanism for this is through the oculomotor system. We reanalyzed our findings to investigate the relationship between baseline oculomotor parameters and change in refraction, and between the change in these values and change in refraction. METHODS: Children who wore progressive lenses (N = 38; 26 with +1.50 D addition, and 16 with +2.00 D addition) or single-vision lenses (N = 32) had refraction, distance heterophoria, near heterophoria, and stimulus AC/A ratio measured prospectively over a 2-year period. RESULTS: There were no statistically significant correlations between baseline heterophoria or AC/A values and change in refractive error. Distance and near heterophoria did not change significantly over the 2 years of the experiment; AC/A ratio decreased significantly, but in an equivalent manner for both groups. In the combined progressive lens group, change toward more exophoria at near was associated with less myopia progression. However three-way analysis of variance (visit x lens type x esophoria/nonesophoria) showed significant main effects in refraction over all five visits. There was a significant interaction between lens type and visits; there was no significant interaction between lens type and esophoria/ nonesophoria grouping. Three-way analysis of variance showed a statistically significant decrease of AC/A ratio over all five visits; there was no interaction of visit by lens or visit by phoria grouping. CONCLUSIONS: Although there were no statistically significant differences between esophoric and nonesophoric subjects, there was only 46% as much myopia progression in the progressive lenses-esophoric group as in the progressive lenses-nonesophoric group. In addition, there were no differences in AC/A ratio between esophoric and nonesophoric subjects. However these findings are not definitive. This experiment was not designed to discriminate between refraction and oculomotor changes in esophoric and nonesophoric subjects and lacked the necessary statistical power to do so.

Analysis of Variance↗

Blurred roles and permeable boundaries: the experience of multidisciplinary working in community mental health.

This paper reports on an investigation of three interdisciplinary mental health teams. The discussion of the responses highlights the boundaries that exist between different professional roles and areas of responsibility. Whereas there is some evidence of role blurring, which was welcomed by a few respondents, others sought to preserve their own professional identity within the multidisciplinary environment. In a paradoxical sense, the lack of managerial direction and the encouragement of generic working seemed to make some respondents all the more insistent on separate professional identities. We conclude that, far from being a relic of the past or a product of 'ingrained attitudes', boundaries between professions are actively encouraged by the experience of interdisciplinary modes of working.

Journal Article↗

Cone-mediated multifocal electroretinogram in early age-related maculopathy and its relationships with subjective macular function tests.

PURPOSE: To investigate the multifocal electroretinogram (mfERG) and subjective function in early age-related maculopathy (ARM). METHODS: Seventeen subjects with early ARM with visual acuity (VA) of 6/12 or better and 20 age-matched control subjects were examined. We assessed mfERGs, high and low contrast distance VA, near VA, low luminance VA, contrast sensitivity, saturated and desaturated Panel D-15 and visual fields (mean sensitivity). The mfERG responses were analysed by comparing central-overall (method 1) and superior-inferior (method 2) ratios. RESULTS: The mfERG did not discriminate between the groups whereas colour vision (tritan deficiency), contrast sensitivity, and high contrast and low contrast VA showed significantly reduced responses for the early ARM group compared with the control group (p < or = 0.01). The mfERG first-order kernel responses correlated significantly with the desaturated D-15 in both methods (r = -0.5, p < or = 0.05). Fundus grading was not correlated with the mfERG measures. CONCLUSIONS: Although the mfERG correlated significantly with the desaturated D-15 in early ARM, suggesting it operates at a sensitive level, it failed to discriminate between the control and ARM groups. In our sample, the subjective function measures were more sensitive than the mfERG measures.

Aged↗

The rod-mediated multifocal electroretinogram in aging and in early age-related maculopathy.

PURPOSE: To measure function with the rod-mediated multifocal electroretinogram (mfERG) in younger and older subjects with normal vision and with early age-related maculopathy (ARM). METHODS: Thirty subjects were studied: 10 healthy subjects with a mean age of 31 years (young group), 10 healthy subjects with a mean age of 71 years (old group), and 10 early ARM subjects with a mean age of 71 years (early ARM group). The influence of cataract was approximated by retesting five subjects of the young group through an 0.3 neutral density filter (ND filter group). We analyzed first-order N1P1-amplitude and P1-implicit time (P1-IT) mfERG responses and correlated them with funduscopic changes as defined by the Age-Related Eye Disease Study (AREDS) group. RESULTS: Averaged concentric ring P1-ITs were significantly delayed in the old (p = 0.02) and early ARM (p < 0.001) compared with the young group and in the early ARM group compared with the old and ND group (p < or = 0.01). There were no significant differences in N1P1-amplitudes between groups, but there was a significant location effect for all groups with highest mean amplitudes for the most peripheral ring of hexagons (p < 0.01). Significantly delayed overall P1-ITs (p < 0.05) were correlated with progressive funduscopic changes. CONCLUSIONS: Aging and early ARM affects the rod-mediated mfERG, and there is good correlation with funduscopic changes. Although a lens effect cannot be excluded, a neuronal transmission alteration at the postreceptoral level is suggested.

Adult↗

Preferred walking speed for assessment of mobility performance: sighted guide versus non-sighted guide techniques.

BACKGROUND: If visually impaired people had their sight fully restored, it is assumed that they would walk at their optimal speeds. Previous mobility studies have used preferred walking speed (PWS) to measure walking efficiency of visually impaired adults. Therefore, the actual speeds that visually impaired people adopt on a route can be expressed as a percentage of their preferred walking speed (PPWS). There have been two approaches used in previous studies for determining preferred walking speed. 1. the sighted guide technique (SG), which requires a subject to walk with a sighted guide and regard the latter as a perfect mobility aid, with the subject setting the preferred (optimal) walking pace 2. the non-sighted guide technique (NonSG), which requires a subject to walk alone along an unobstructed straight path for a certain distance, adopting the preferred (optimal) walking speed. There is some debate on which technique is the better. This study was conducted to determine if there is any difference between the two techniques for determining visually impaired subjects' preferred walking speeds. METHODS: Fourteen visually impaired adult subjects were recruited. PWS was determined by recording the time taken for a subject to walk an unobstructed, straight 20-metre corridor path using each technique. RESULTS: There was no significant difference in PWS using the sighted guide and non-guided techniques. CONCLUSIONS: Either the SG or NonSG techniques can be used to determine PWS for a heterogeneous group of visually impaired subjects.

Journal Article↗

Factors that influence the medication decision making of persons with HIV/AIDS: a taxonomic exploration.

It is well known that patients often alter their medication regimens and that these changes may have profound consequences for their health outcomes. Not so well known are the factors that influence the medication decision making of persons managing their own treatment in their day-to-day home situations. In this study, persons living with HIV/AIDS (PLWH) were asked about factors that affected the taking of their medications. Using semistructured interviews in this study of 57 PLWH, the authors used intensive analysis of the narratives to create taxonomies of the barriers and facilitators to taking HIV medications and the decisions that were involved. Categories of identified facilitators included motivation, factors of faith, routines, and others' influences. Categories of identified barriers included perceptions, psycho-emotional issues, provider/clinic issues, interpersonal factors, and disease and treatment factors. This study showed medication decision making to be a complex process, influenced by often-competing life and treatment issues and affected by participants' beliefs and values. These findings call for research into the everyday selfcare of PLWH to understand the reasoned decision-making that PLWH use in managing not only their medications but also their lives.

Adult↗

Interdisciplinary work in community mental health.

The idea of mental health and social care staff working within clearly defined roles is often frowned upon as poor and retrogressive practice, out of step with the government's modernisation agenda. But as this article points out, increasingly blurred roles in already stressful and demanding clinical teams can be counterproductive, with practitioners becoming entrenched in their own perception of their particular roles and less flexible in their work. Conversely, well-defined boundaries and clearly defined roles can be supportive and enabling, providing a containing structure for teams to work within.

Community Mental Health Centers↗