Notas sobre el "primum cognitum" en Cayetano y su vínculo con la metafísica

Cayetano tuvo un papel protagónico en los debates intelectuales de su época (s. XVI), destacándose como un auténtico adalid del tomismo; inclusive muchas de sus tesis pasaron a formar parte de tal doctrina, las cuales –a veces matizadas y otras no tanto– perviven hasta nuestros días. Entre los diversos temas que afrontó se destaca su particular noción de primum cognitum. Aquí, partimos del hecho de que la tradición tomista no ha visto mayores inconvenientes en equiparar lo que entienden Cayetano y el Aquinate por el ens primo cadit; empero nosotros estamos en condiciones de afirmar que tal equiparación al menos es problemática. En este sentido, nos ocuparemos de realizar un primer acercamiento al tema del ente primer conocido cayetaniano para intentar mostrar su real significado. Asimismo, procuraremos ver, ayudados por los aportes de algunos estudiosos contemporáneos –en especial el de Lawrence Dewan–, hasta qué punto tal noción se corresponde o no con los desarrollos teóricos de Tomás de Aquino, sobre todo con el vínculo entre el primer conocido y el ente como objeto de la metafísica.

Modeling and reasoning with qualitative comparative clinical knowledge

The number of clinical trials reports is increasing rapidly due to a large number of clinical trials being conducted; it, therefore, raises an urgent need to utilize the clinical knowledge contained in the clinical trials reports. In this paper, we focus on the qualitative knowledge instead of quantitative knowledge. More precisely, we aim to model and reason with the qualitative comparison (QC for short) relations which consider qualitatively how strongly one drug/therapy is preferred to another in a clinical point of view. To this end, first, we formalize the QC relations, introduce the notions of QC language, QC base, and QC profile; second, we propose a set of induction rules for the QC relations and provide grading interpretations for the QC bases and show how to determine whether a QC base is consistent. Furthermore, when a QC base is inconsistent, we analyze how to measure inconsistencies among QC bases, and we propose different approaches to merging multiple QC bases. Finally, a case study on lowering intraocular pressure is conducted to illustrate our approaches.

Involvement of MAPKs in endostatin-mediated regulation of blood-retinal barrier function

Purpose: This study aimed to evaluate the effects of endostatin on tight junction (TJ) integrity in retinal microvascular endothelial cells (RMECs) in vitro and in vivo. Moreover, it was hypothesized that endostatin-induced occludin upregulation regulated VEGF(165)-mediated increases in endothelial cell permeability and involved activation of the MAPK signaling cascade. Endostatin is a 20-kDa fragment of collagen XVIII that has been shown to be efficacious in the eye by preventing retinal neovascularization. Endostatin is a specific inhibitor of endothelial cell proliferation, migration, and angiogenesis and has been reported to reverse VEGF-mediated increases in vasopermeability and to promote integrity of the blood-retinal barrier (BRB). In order to determine the mechanism of endostatin action on BRB integrity, we have examined the effects of endostatin on a number of intracellular pathways implicated in endothelial cell physiology. Methods: C57/Bl6 mice were injected with VEGF(165) and/or endostatin, and the distribution of occludin staining was determined using retinal flatmounts. Western blot analysis of RMECs treated with VEGF(165) and/or endostatin was used to determine changes in occludin expression and p38 MAPK and extracellular regulated kinase (ERK1/ERK2 MAPK) activation, while FD-4 flux across the RMEC monolayer was used to determine changes in paracellular permeability. Results: Endostatin prevented the discontinuous pattern of occludin staining observed at the retinal blood vessels of mice administered an intraocular injection of VEGF(165). It was shown that endostatin activated p38 MAPK 5 min after addition to RMECs and continued to do so for approximately 30 min. Endostatin was also shown to activate ERK1/ERK2 5 min after addition and continued to do so, albeit with less potency, up to and including 15 min after addition. Inhibition of p38 MAPK and ERK1/ERK2 prevented endostatin's ability to upregulate levels of occludin expression. Inhibition of these key signaling molecules was shown to prevent endostatin's ability to protect against VEGF(165)- mediated increases in paracellular permeability in vitro. However, it appears that p38 MAPK may play a more important role in VEGF-mediated permeability, as inhibition of ERK1/ERK2 will not prevent VEGF(165)- mediated permeability compared with control ( untreated) cells or cells treated with both a p38 MAPK inhibitor and VEGF(165). Conclusions: Occludin is important for the maintenance of tight junction integrity in vivo. In a p38 MAPK and ERK1/ERK2 dependent manner, endostatin was shown to upregulate the levels of expression of the tight junction protein occludin. Inhibition of these key MAPK components may prevent endostatin's ability to decrease VEGF(165)-induced paracellular permeability.

Selective Inhibition of Retinal Angiogenesis by Targeting PI3 Kinase

Ocular neovascularisation is a pathological hallmark of some forms of debilitating blindness including diabetic retinopathy, age related macular degeneration and retinopathy of prematurity. Current therapies for delaying unwanted ocular angiogenesis include laser surgery or molecular inhibition of the pro-angiogenic factor VEGF. However, targeting of angiogenic pathways other than, or in combination to VEGF, may lead to more effective and safer inhibitors of intraocular angiogenesis. In a small chemical screen using zebrafish, we identify LY294002 as an effective and selective inhibitor of both developmental and ectopic hyaloid angiogenesis in the eye. LY294002, a PI3 kinase inhibitor, exerts its anti-angiogenic effect in a dose-dependent manner, without perturbing existing vessels. Significantly, LY294002 delivered by intraocular injection, significantly inhibits ocular angiogenesis without systemic side-effects and without diminishing visual function. Thus, targeting of PI3 kinase pathways has the potential to effectively and safely treat neovascularisation in eye disease.

Good news-bad news:the Yin and Yang of immune privilege in the eye

The eye and the brain are prototypical tissues manifesting immune privilege (IP) in which immune responses to foreign antigens, particularly alloantigens are suppressed, and even completely inhibited. Explanations for this phenomenon are numerous and mostly reflect our evolving understanding of the molecular and cellular processes underpinning immunological responses generally. IP is now viewed as a property of many tissues and the level of expression of IP varies not only with the tissue but with the nature of the foreign antigen and changes in the limited conditions under which privilege can operate as a mechanism of immunological tolerance. As a result, IP functions normally as a homeostatic mechanism preserving normal function in tissues, particularly those with highly specialized function and limited capacity for renewal such as the eye and brain. However, IP is relatively easily bypassed in the face of a sufficiently strong immunological response, and the privileged tissues may be at greater risk of collateral damage because its natural defenses are more easily breached than in a fully immunocompetent tissue which rapidly rejects foreign antigen and restores integrity. This two-edged sword cuts its swathe through the eye: under most circumstances, IP mechanisms such as blood-ocular barriers, intraocular immune modulators, induction of T regulatory cells, lack of lymphatics, and other properties maintain tissue integrity; however, when these are breached, various degrees of tissue damage occur from severe tissue destruction in retinal viral infections and other forms of uveoretinal inflammation, to less severe inflammatory responses in conditions such as macular degeneration. Conversely, ocular IP and tumor-related IP can combine to permit extensive tumor growth and increased risk of metastasis thus threatening the survival of the host.

Clinical and cost-effectiveness of internal limiting membrane peeling for patients with idiopathic full thickness macular hole. Protocol for a Randomised Controlled Trial:FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study)

Background: A full-thickness macular hole (FTMH) is a common retinal condition associated with impaired vision. Randomised controlled trials (RCTs) have demonstrated that surgery, by means of pars plana vitrectomy and post-operative intraocular tamponade with gas, is effective for stage 2, 3 and 4 FTMH. Internal limiting membrane (ILM) peeling has been introduced as an additional surgical manoeuvre to increase the success of the surgery; i.e. increase rates of hole closure and visual improvement. However, little robust evidence exists supporting the superiority of ILM peeling compared with no-peeling techniques. The purpose of FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study) is to determine whether ILM peeling improves the visual function, the anatomical closure of FTMH, and the quality of life of patients affected by this disorder, and the cost-effectiveness of the surgery. Methods/Design: Patients with stage 2-3 idiopathic FTMH of less or equal than 18 months duration (based on symptoms reported by the participant) and with a visual acuity = 20/40 in the study eye will be enrolled in this FILMS from eight sites across the UK and Ireland. Participants will be randomised to receive combined cataract surgery (phacoemulsification and intraocular lens implantation) and pars plana vitrectomy with postoperative intraocular tamponade with gas, with or without ILM peeling. The primary outcome is distance visual acuity at 6 months. Secondary outcomes include distance visual acuity at 3 and 24 months, near visual acuity at 3, 6, and 24 months, contrast sensitivity at 6 months, reading speed at 6 months, anatomical closure of the macular hole at each time point (1, 3, 6, and 24 months), health related quality of life (HRQOL) at six months, costs to the health service and the participant, incremental costs per quality adjusted life year (QALY) and adverse events. Discussion: FILMS will provide high quality evidence onthe role of ILM peeling in FTMH surgery. © 2008 Lois et al; licensee BioMed Central Ltd.

Heavier-than-water silicone oil mixture as a long-term tamponade agent:A pilot study

Purpose: To evaluate the tamponade effect on the retina of a heavier-than-water silicone oil mixture and to compare it with the effect of silicone oil. Methods: Prospective, non-randomised, comparative pilot study. Phakic/pseudophakic patients with retinal detachment undergoing vitrectomy with Densiron 68 or silicone oil were recruited. The 'separation volume', defined as the relative volume of the space between intraocular tamponade agent and retina, was estimated using magnetic resonance imaging in both groups and compared. Results: Nine participants were included; 4 received silicone oil and 5 Densiron 68. The mean separation volume was statistically significantly larger in the silicone oil group (0.477 ± 0.419 cm ) than in the Densiron group (0.042 ± 0.013 cm ; p = 0.014). Conclusions: In this study Densiron achieved an excellent tamponade effect in the retina. © 2011 S. Karger AG, Basel.

Punctate inner choroidopathy

Punctate inner choroidopathy (PIC) is a relatively uncommon inflammatory multifocal chorioretinopathy that affects predominantly young myopic women. It is characterized by the presence of multiple, small, well-defined, yellow-white fundus lesions frequently limited to the posterior pole in the absence of flare and inflammatory cells in the anterior chamber or vitreous cavity. Most patients with PIC do not require treatment, as the disease does not often threaten vision; however, when subfoveal choroidal neovascular membrane (CNV) ensues, patients usually lose sight rapidly, requiring immediate care. Treatment modalities that have been used to manage patients with PIC and subfoveal CNV include systemic and local steroids, other immunosuppressant agents, laser photocoagulation, photodynamic therapy, submacular surgery and, most recently, anti-vascular endothelial growth factor therapy. To date, however, there is no clear consensus on the effective therapy. Further research into this area, as well as on the cause and possible predisposing factors for PIC, is warranted. © 2011 Elsevier Inc.

Pseudophakic retinal detachment

Pseudophakic retinal detachment is a rare, but potentially serious, complication of cataract surgery. The incidence of pseudophakic retinal detachment following current surgical techniques of cataract extraction, including extracapsular cataract extraction by nuclear expression and phacoemulsification, is lower than that found after intracapsular cataract extraction. The risk of pseudophakic retinal detachment appears to be increased in myopic patients, in those patients in whom vitreous loss had occurred at the time of cataract surgery, and in patients undergoing Nd:YAG posterior capsulotomy. Most cases present to the clinician when the macula is already detached and the central vision is affected. When evaluating patients with pseudophakic retinal detachment, the fundal view is often impaired by anterior or posterior capsular opacification, reflections related to the intraocular lens, or poor mydriasis. Scleral buckling, pneumatic retinopexy, and primary pars plana vitrectomy, with or without combined scleral buckling, are the surgical techniques used to treat pseudophakic retinal detachment. Anatomical success rates are high after vitreo-retinal surgery for pseudophakic retinal detachment, although a smaller proportion of patients recover good vision following surgery. © 2003 Elsevier Inc. All rights reserved.

New surgical approach in the management of pseudophakic malignant glaucoma

Purpose: To describe a new surgical approach in the management of pseudophakic malignant glaucoma. Design: Noncomparative case series. Participants: Five consecutive patients with pseudophakic malignant glaucoma. Methods: All patients underwent zonulo-hyaloido-vitrectomy. The procedure involves the performance of zonulectomy, hyaloidectomy, and anterior vitrectomy (zonulo-hyaloido-vitrectomy) through a peripheral iridectomy or iridotomy via the anterior chamber. Main Outcome Measures: Medications, visual acuity, intraocular pressure, and anterior and posterior segment findings were recorded before and after surgery. Results: Resolution of the malignant glaucoma was achieved in all cases. No recurrences were observed after a median follow-up of 5.5 months (range, 1-9 months). In one patient with extensive anterior synechiae, bleb failure occurred after the resolution of the malignant glaucoma. This patient was treated successfully with a guarded filtration procedure supplemented with 5-fluorouracil. No other complications were observed. Conclusions: Zonulo-hyaloido-vitrectomy via the anterior segment appears to be an alternative option in the treatment of patients with pseudophakic malignant glaucoma. © 2001 by the American Academy of Ophthalmology.

Immunophenotypic shift in a case of mycosis fungoides with vitreous invasion

The case of an 82-year-old man who developed intraocular extension from mycosis fungoides, a cutaneous T-cell lymphoma, is presented. The patient died soon after intra-ocular involvement occurred. Immunohistochemistry of a skin biopsy, taken early in the course of the disease, disclosed a predominance of T cells with a helper/inducer phenotype (CD4). However, an intraocular infiltrate obtained 7 years later contained mostly T cells with a suppressor/cytotoxic phenotype (CD8). The occurrence of ocular invasion, the change in immunophenotype, and the predominant proliferation of CD8 lymphocytes may have been related to the poor outcome in this patient.

A new model of posterior capsule opacification in rodents

PURPOSE. To describe a new model of posterior capsule opacification (PCO) in rodents METHODS. An extracapsular lens extraction (ECLE), by continuous curvilinear capsulorrhexis and hydrodissection, was performed in 42 consecutive Brown Norway rats. Animals were killed at 0, 6, and 24 hours and 3, 7, and 14 days after surgery. Eyes were enucleated and processed for light microscopy and immunohistochemistry. RESULTS. In 34 (81%) of the animals the operated eye appeared well healed before death, with a clear cornea and a well-formed anterior chamber. In eight (19%) there was no view of anterior segment structures because of hyphema, fibrin, or corneal opacification. PCO was clinically evident 3 days after ECLE and was present in all animals at 2 weeks. Immediately after ECLE, lens epithelial cells (LECs) were present in the inner surface of the anterior capsule and lens bow. Twenty-four hours after surgery, LECs started to migrate toward the center of the posterior capsule. At 3 days, multilayered LECs, some spindle shaped, were present throughout the lens capsule. Capsular wrinkling was apparent. Lens fibers and Soemmering's ring were observed in all animals 14 days after surgery, indicating some degree of cellular differentiation. Activated macrophages were present in greater numbers at 3 and 14 days after surgery (P <0.05), when proliferation and migration of LECs appeared to be greatest, and lens fiber differentiation was evident, respectively. CONCLUSIONS. In rodents PCO occurs after ECLE and is associated with low-grade inflammation, mostly of mononuclear macrophages. Although no intraocular lens implantation was performed, this model appears to be valuable for studying the sequence of events that leads to PCO after cataract surgery and the extracellular matrix cues that promote lens fiber differentiation.

Iris cysts in children:Classification, incidence, and management. The 1998 Torrence A Makley Jr Lecture

Background - Iris cysts in children are uncommon and there is relatively little information on their classification, incidence, and management. Methods - The records of all children under age 20 years who were diagnosed with iris cyst were reviewed and the types and incidence of iris cysts of childhood determined. Based on these observations recommendations were made regarding management of iris cysts in children. Results - Of 57 iris cysts in children, 53 were primary and four were secondary. There were 44 primary cysts of the iris pigment epithelium, 34 of which were of the peripheral or iridociliary type, accounting for 59% of all childhood iris cysts. It was most commonly diagnosed in the teenage years, more common in girls (68%), was not recognised in infancy, remained stationary or regressed, and required no treatment. The five mid-zonal pigment epithelial cysts were diagnosed at a mean age of 14 years, were more common in boys (83%), remained stationary, and required no treatment. The pupillary type of pigment epithelial cyst was generally recognised in infancy and, despite involvement of the pupillary aperture, also required no treatment. There were nine cases of primary iris stromal cysts, accounting for 16% of all childhood iris cysts. This cyst was usually diagnosed in infancy, was generally progressive, and required treatment in eight of the nine cases, usually by aspiration and cryotherapy or surgical resection. Among the secondary iris cysts, two were post-traumatic epithelial ingrowth cysts and two were tumour induced cysts, one arising from an intraocular lacrimal gland choristoma and one adjacent to a peripheral iris naevus. Conclusions - Most iris cysts of childhood are primary pigment epithelial cysts and require no treatment. However, the iris stromal cyst, usually recognised in infancy, is generally an aggressive lesion that requires treatment by aspiration or surgical excision.

Trifocal uveal melanoma

PURPOSE: To report the singular case of a patient who developed three noncontiguous uveal melanomas over a 30-year period. METHOD: Case report. RESULT: Systemic evaluation of a 50-year-old man with an iris melanoma and bilateral choroidal melanomas disclosed no evidence of metastases or other primary neoplastic disease. CONCLUSION: Although rare, the possibility of bilateral and multifocal uveal melanoma should be recognized.

Cavitary melanoma of the ciliary body. A study of eight cases

Purpose: The authors present the unique clinical features of cavitary uveal melanoma. Design: Retrospective chart review. Participants: Eight patients with cavitary uveal melanoma. Main Outcome Measures: The clinical, ultrasonographic, and histopathologic features of eight patients with cavitary melanoma of the ciliary body were studied. Results: In all eyes there was a brown ciliary body mass that blocked transmission of light on trans-scleral transillumination. Ocular ultrasonography revealed a large, single hollow cavity (unilocular 'pseudocyst') in five cases and multiple hollow cavities (multilocular 'pseudocyst') in three cases. The cavity occupied a mean of 55% of the entire mass thickness (range, 31%-79%). In five cases, a basal uveal mass was noted on ultrasonography. Four patients underwent tumor resection; one had enucleation, and three had 1251 radioactive plaque treatment. In the five cases confirmed histopathologically, the cavitation was empty, contained erythrocytes, serous fluid, and/or pigment-laden macrophages. In no case was the cavity lined by necrotic tumor, endothelial cells, or epithelial cells. Conclusion: Ciliary body melanoma can develop an intralesional cavity resembling an intraocular cyst. The presence of a solid mass at the base and a thick wall surrounding the cavity can assist in the differentiation of cavitary melanoma from benign cyst.