327 resultados para Beman, Nathan S. S. (Nathan Sidney Smith), 1785-1871.
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Human genetic association studies have shown gene variants in the α5 subunit of the neuronal nicotinic receptor (nAChR) influence both ethanol and nicotine dependence. The α5 subunit is an accessory subunit that facilitates α4* nAChRs assembly in vitro. However, it is unknown whether this occurs in the brain, as there are few research tools to adequately address this question. As the α4*-containing nAChRs are highly expressed in the ventral tegmental area (VTA) we assessed the molecular, functional and pharmacological roles of α5 in α4*-containing nAChRs in the VTA. We utilized transgenic mice α5+/+(α4YFP) and α5-/-(α4YFP) that allow the direct visualization and measurement of α4-YFP expression and the effect of the presence (α5+/+) and absence of α5 (-/-) subunit, as the antibodies for detecting the α4* subunits of the nAChR are not specific. We performed voltage clamp electrophysiological experiments to study baseline nicotinic currents in VTA dopaminergic neurons. We show that in the presence of the α5 subunit, the overall expression of α4 subunit is increased significantly by 60% in the VTA. Furthermore, the α5 subunit strengthens baseline nAChR currents, suggesting the increased expression of α4* nAChRs to be likely on the cell surface. While the presence of the α5 subunit blunts the desensitization of nAChRs following nicotine exposure, it does not alter the amount of ethanol potentiation of VTA dopaminergic neurons. Our data demonstrates a major regulatory role for the α5 subunit in both the maintenance of α4*-containing nAChRs expression and in modulating nicotinic currents in VTA dopaminergic neurons. Additionally, the α5α4* nAChR in VTA dopaminergic neurons regulates the effect of nicotine but not ethanol on currents. Together, the data suggest that the α5 subunit is critical for controlling the expression and functional role of a population of α4*-containing nAChRs in the VTA.
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Diabetic neuropathy is associated with increased morbidity and mortality. To date, limited data in subjects with impaired glucose tolerance and diabetes demonstrate nerve fiber repair after intervention. This may reflect a lack of efficacy of the interventions but may also reflect difficulty of the tests currently deployed to adequately assess nerve fiber repair, particularly in short-term studies. Corneal confocal microscopy (CCM) represents a novel noninvasive means to quantify nerve fiber damage and repair. Fifteen type 1 diabetic patients undergoing simultaneous pancreas-kidney transplantation (SPK) underwent detailed assessment of neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy, corneal sensitivity, and CCM at baseline and at 6 and 12 months after successful SPK. At baseline, diabetic patients had a significant neuropathy compared with control subjects. After successful SPK there was no significant change in neurologic impairment, neurophysiology, QST, corneal sensitivity, and intraepidermal nerve fiber density (IENFD). However, CCM demonstrated significant improvements in corneal nerve fiber density, branch density, and length at 12 months. Normalization of glycemia after SPK shows no significant improvement in neuropathy assessed by the neurologic deficits, QST, electrophysiology, and IENFD. However, CCM shows a significant improvement in nerve morphology, providing a novel noninvasive means to establish early nerve repair that is missed by currently advocated assessment techniques.
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Purpose The aim was to determine the extent of daily disposable contact lens prescribing worldwide and to characterise the associated demographics and fitting patterns. Methods Up to 1,000 survey forms were sent to contact lens fitters in up to 40 countries between January and March every year for five consecutive years (2007 to 2011). Practitioners were asked to record data relating to the first 10 contact lens fits or refits performed after receiving the survey form. Survey data collected since 1996 were also analysed for seven nations to assess daily disposable lens fitting trends since that time. Results Data were collected in relation to 97,289 soft lens fits, of which 23,445 (24.1 per cent) were with daily disposable lenses and 73,170 (75.9 per cent) were with reusable lenses. Daily disposable lens prescribing ranged from 0.6 per cent of all soft lenses in Nepal to 66.2 per cent in Qatar. Compared with reusable lens fittings, daily disposable lens fittings can be characterised as follows: older age (30.0 ± 12.5 versus 29.3 ± 12.3 years for reusable lenses); males are over-represented; a greater proportion of new fits versus refits; 85.9 per cent hydrogel; lower proportion of toric and presbyopia designs and a higher proportion of part-time wear. There has been a continuous increase in daily disposable lens prescribing between 1996 and 2011. The proportion of daily disposable lens fits (as a function of all soft lens fits) is positively related to the gross domestic product at purchasing power parity per capita (r2 = 0.55, F = 46.8, p < 0.0001). Conclusions The greater convenience and other benefits of daily disposable lenses have resulted in this modality capturing significant market share. The contact lens field appears to be heading toward a true single-use-only, disposable lens market.
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Moderator Opening The early focus of contact lens wear and ocular health was on oxygen delivery. However, as we learn more about how the eye works, and investigate how the contact lens interacts with the cornea, the role of the tear film has risen in prominence. A healthy tear film is critical for normal ocular homeostasis, and abnormalities of the tear film are the primary cause of dry eye. In order to improve patient eye health and comfort during lens wear, we need to further elucidate the relationship among contact lenses, contact lens solutions, the tear film, and the corneal epithelium, and find ways to maintain homeostasis of the ocular surface. In this section, we review the latest data and opinions on this complex relationship between contact lenses and lens care solutions
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Purpose To determine the extent of rigid contact lens fitting worldwide and to characterize the associated demographics and fitting patterns. Methods Survey forms were sent to contact lens fitters in up to 40 countries between January and March every year for five consecutive years (2007 to 2011). Practitioners were asked to record data relating to the first 10 contact lens fits or refits performed after receiving the survey form. Survey data collected between 1996 and 2011 were also analyzed to assess rigid lens fitting trends in seven nations during this period. Results Data were obtained for 12,230 rigid and 100,670 soft lens fits between 2007 and 2011. Overall, rigid lenses represented 10.8% of all contact lens fits, ranging from 0.2% in Lithuania to 37% in Malaysia. Compared with soft lens fits, rigid lens fits can be characterized as follows: older age (rigid, 37.3 ± 15.0 years; soft, 29.8 ± 12.4 years); fewer spherical and toric fits; more bifocal/multifocal fits; less frequent replacement (rigid, 7%; soft, 85%); and less part-time wear (rigid, 4%; soft, 10%). High-Dk (contact lens oxygen permeability) (36%) and mid-Dk (42%) materials are predominantly used for rigid lens fitting. Orthokeratology represents 11.5% of rigid contact lens fits. There has been a steady decline in rigid lens fitting between 1996 and 2011. Conclusions Rigid contact lens prescribing is in decline but still represents approximately 10% of all contact lenses fitted worldwide. It is likely that rigid lenses will remain as a viable, albeit increasingly specialized, form of vision correction.
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Objectives To characterize toric contact lens prescribing worldwide. Methods Up to 1,000 survey forms were sent to contact lens fitters in up to 39 countries between January and March every year for 5 consecutive years (2007–2011). Practitioners were asked to record data relating to the first 10 contact lens fits or refits performed after receiving the survey form. Only data for toric and spherical soft lens fits were analyzed. Survey data collected since 1996 were also analyzed for 7 nations to assess toric lens fitting trends since that time. Results Data were collected in relation to 21,150 toric fits (25%) and 62,150 spherical fits (75%). Toric prescribing ranged from 6% of lenses in Russia to 48% in Portugal. Compared with spherical fittings, toric fittings can be characterized as follows: older age (29.8 ± 11.4 years vs. 27.6 ± 10.8 years for spherical lenses); men are overrepresented (38% vs. 34%); greater proportion of new fits (39% vs. 32%); use of silicone hydrogel lenses (49% vs. 39%); and lower proportion of daily disposable lenses (14% vs. 28%). There has been a continuous increase in toric lens prescribing between 1996 and 2011. The proportion of toric lens fits was positively related to the gross domestic product at purchasing power parity per capita for year 2011 (r2 = 0.21; P=0.004). Conclusions At the present time, in the majority of countries surveyed, toric soft contact lens prescribing falls short of that required to correct clinically significant astigmatism (≥0.75 diopters) in all lens wearers.
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Objectives To characterize and discover the determinants of the frequency of wear (FOW) of contact lenses. Methods Survey forms were sent to contact lens fitters in up to 40 countries between January and March every year for 5 consecutive years (2007–2011). Practitioners were asked to record data relating to the first 10 contact lens fits or refits performed after receiving the survey form. Only data for daily wear lens fits were analyzed. Results Data were collected in relation to 74,510 and 9,014 soft and rigid lens fits, respectively. Overall, FOW was 5.9±1.7 days per week (DPW). When considering the proportion of lenses worn between one to seven DPW, the distribution for rigid lenses is skewed toward full-time wear (7 DPW), whereas the distribution for soft daily disposable lenses is perhaps bimodal, with large and small peaks at seven and two DPW, respectively. There is a significant variation in FOW among nations (P<0.0001), ranging from 6.8±1.0 DPW in Greece to 5.1±2.5 DPW in Kuwait. For soft lenses, FOW increases with decreasing age. Females (6.0±1.6 DPW) wear lenses more frequently than males (5.8±1.7 DPW) (P=0.0002). FOW is greater among those wearing presbyopic corrections (6.1±1.4 DPW) compared with spherical (5.9±1.7 DPW) and toric (5.9±1.6 DPW) designs (P<0.0001). FOW with hydrogel peroxide systems (6.4±1.1 DPW) was greater than that with multipurpose systems (6.2±1.3 DPW) (P<0.0001). Conclusions Numerous demographic and contact lens–related factors impact FOW. There may be a future trend toward a lower FOW associated with the increasing popularity of daily disposable lenses.
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As Drs Patel and McGhee intimate, the original nerve mapping technique they described 1 was tedious and time-consuming, requiring the capture of hundreds of separate images and many hours of manual montaging to form a confluent map. The maps they published also had distracting component image delineation. It is for these reasons that a number of research groups have sought to develop automated techniques for generating these nerve maps (Table 1).2–6...
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While vital staining remains a cornerstone in the diagnosis of ocular disease and contact lens complications, there are many misconceptions regarding the properties of commonly used dyes by eye-care practitioners and what is and what is not corneal staining after instillation of sodium fluorescein. Similarly, the proper use and diagnostic utility of rose Bengal and lissamine green B, the other two ophthalmic dyes commonly used for assessing ocular complications, have similarly remained unclear. Due to the limitations of vital stains for definitive diagnosis, concomitant signs and symptoms in addition to a complete patient history are required. Over the past decade, there have been many reports of a type of corneal staining—often referred to as solution-induced corneal staining (SICS)—that is observed with the use of multipurpose solutions in combination with soft lenses, more specifically silicone hydrogel lenses. Some authors believe that SICS is a sign of lens/solution incompatibility; however, new research shows that SICS may be neither a measure of lens/solution biocompatibility nor ‘true’ corneal staining, as that observed in pathological situations. A large component of SICS may be a benign phenomenon, known as preservative-associated transient hyperfluorescence (PATH). There is a lack of correlated signs and/or symptoms with SICS/PATH. Several properties of SICS/PATH, such as appearance and duration, differentiate it from pathological corneal staining. This paper reviews the properties of vital stains, their use and limitations in assessment of the ocular surface, the aetiology of corneal staining, characteristics of SICS/PATH that differentiate it from pathological corneal staining and what the SICS/PATH phenomenon means for contact lens-wearing patients.
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Ever since sodium fluorescein (‘fluorescein’ [FL]) was first used to investigate the ocular surface over a century ago, the term ‘staining’ has been taken to mean the presence of ocular surface fluorescence [1]. This term has not been necessarily taken to infer any particular mechanism of causation, and indeed, can be attributed to a variety of possible aetiologies [2]. In recent times, there has been considerable interest in a form of ocular surface fluorescence seen in association with the use of certain combinations of soft contact lenses and multipurpose solutions. The first clinical account of this phenomenon was reported by Jones et al. [3], which was followed by a more formal investigation by the same author in 2002 [4]. Jones et al described this appearance as a ‘classic solution-based toxicity reaction’. Subsequently, this appearance has come to be known as ‘solution-induced corneal staining’ or more recently by the acronym ‘SICS’ [5]. The term SICS is potentially problematic in that from a cell biology point of view, there is an inference that ‘staining’ means the entry of a dye into corneal epithelial cells. Morgan and Maldonado-Codina [2] noted there was no foundation of solid scientific literature underpinning our understanding of the true basic causative mechanisms of this phenomenon; since that time, further work has been published in this field [6] and [7] but questions still remain about the precise aetiology of this phenomenon...
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A response to: "Re: Putting vital stains in context" by Eric Papas & Lyndon Jones, published in the same issue of this journal. "There has been considerable discussion in recent times about the origins of solution-induced corneal staining (SICS) and I welcome this opportunity to further clarify some points raised in my paper1 in relation to certain issues highlighted by Drs Papas and Jones.2 Part of the difficulty in understanding these phenomena relates to the imprecise terminology used. For example, Drs Papas and Jones state ‘. . . SICS..."
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A response to "Re: Putting vital stains in context" by Charles W McMonnies, published in the same issue of this journal. "I thank Professor McMonnies for his thoughtful comments,1 which rightly forcemeto more directly address the clinical ramifications of solution-induced corneal staining (SICS). I concur with his observation that determining whether the staining can be attributed to preservative-associated transient hyperfluorescence (PATH) or true pathology can be difficult in a typical clinical situation, perhaps requiring two visits in a single day. There is no easy answer to this dilemma..."
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The report of this subcommittee concerns the impact of contact lenses (CLs) on the ocular surface, with a particular emphasis on CL discomfort (CLD). We define the ocular surface, its regional anatomy, and the physiological responses of each region to CL wear.
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In this, the 10th anniversary of the introduction of silicone hydrogel contact lenses onto the market, it is perhaps timely to attempt to reconcile the apparently disparate results from different authors in relation to the incidence of keratitis with silicone hydrogel lenses and indeed, with contact lenses in general. In attempting to understand the findings of these various studies, we propose that consideration be given to the competing effects of an improved physiological response due to increased corneal oxygenation with these lenses versus their mechanical impact...