Funciones cognitivas y terapia electroconvulsiva en pacientes psiquiátricos con enfermedad afectiva / Cognitive functions and electroconvulsive therapy in affective psychiatric patients / Funções cognitivas e terapia eletroconvulsiva em pacientes psiquiátricos com doenças afetiva

Objetivo: la terapia electroconvulsiva (TEC) se ha considerado un tratamiento seguro y eficaz para episodios de depresión mayor, para episodios maníacos y otros trastornos psiquiátricos serios. El estudio describe los efectos cognitivos de la TEC en pacientes referidos para tratamiento a una clínica privada. Metodología: estudio descriptivo del tipo de serie de casos. En cada participante se realizó una evaluación basal antes del inicio de la TEC y otras dos (una a la semana y otra a los seis meses) después de terminado el ciclo de tratamientos, para describir el efecto de la TEC frontotemporal bilateral en la función neurocognitiva mediante el cambio, desde el estado basal hasta la evaluación final en los dominios de memoria, velocidad psicomotora, tiempo de reacción, atención compleja y flexibilidad cognoscitiva, así como en la función cognoscitiva global; y determinar su seguridad por el reporte de eventos adversos. La evaluación cognitiva se realizó con una batería de pruebas neuropsicológicas y la severidad de la enfermedad psiquiátrica se evaluó con la escala Clinical Global Impression Severity (CGI-S). Se incluyeron seis pacientes remitidos para tratamiento durante el periodo de seis meses. Resultados: no se observaron diferencias estadísticamente significativas entre las medianas de las evaluaciones de CGI-S, ni de la función cognitiva global, así como de ninguno de los dominios evaluados. Conclusiones: la TEC no produjo cambios en las funciones cognitivas analizadas en los seis pacientes estudiados.

Objective: Electroconvulsive therapy (ECT) has been considered a safe and effective treatment for depression, manic episodes, and other serious psychiatric conditions. Its main reported side effect has been cognitive impairment. This study describes the cognitive effects of ECT in psychiatric patients referred for treatment at a private clinic. Methodology: Descriptive case series study. A baseline assessment conducted before starting ECT, and another two (at one week and at six months) after completing the treatment cycle were used to describe the effects of frontotemporal bilateral ECT on neurocognitive function in terms of the change from the baseline to the final assessment in the domains of memory, psychomotor speed, reaction time, complex attention, and cognitive flexibility, as well as global cognitive function, as well as to determine ECT's safety by reporting adverse events. Cognitive assessment was conducted with a neuropsychological test battery and severity of psychiatric illness with the Clinical Global Impression-Severity scale (CGI-S). Six patients referred for treatment during six months were included. Results: No statistically significant differences were observed between the medians of the evaluations of CGI-S scale, global cognitive function or any of the domains evaluated. Conclusions: ECT did not produce changes in the cognitive functions assessed in the six studied patients.

Objetivo: a terapia eletroconvulsiva (TEC) se há considerado um tratamento seguro e eficaz para episódios de depressão maior, para episódios maníacos e outros transtornos psiquiátricos sérios. O estudo descreve os efeitos cognitivos da TEC em pacientes referidos para tratamento a uma clínica privada. Metodologia: estudo descritivo do tipo de série de casos. Em cada participante se realizou uma avaliação basal antes do início da TEC e outras dois (uma em uma semana e outra aos seis meses) depois de terminado o ciclo de tratamentos, para descrever o efeito da TEC frontotemporal bilateral na função neurocognitiva mediante a mudança, desde o estado basal até a avaliação final nos domínios de memória, velocidade psicomotora, tempo de reação, atenção complexa e flexibilidade cognoscitiva, assim como na função cognoscitiva global; e determinar sua segurança pelo reporte de eventos adversos. A avaliação cognitiva se realizou com uma bateria de provas neuropsicológicas e a severidade da doença psiquiátrica se avaliou com a escala Clinical Global Impression Severity (CGI-S). Se incluíram seis pacientes remitidos para tratamento durante o período de seis meses. Resultados: não se observaram diferencias estatisticamente significativas entre as média das avaliações de CGI-S, nem da função cognitiva global, assim como de nenhum dos domínios avaliados. Conclusões: a TEC não produziu mudanças nas funções cognitivas analisadas nos seis pacientes estudados.

Oxidative stress and genotoxicity induced by ketorolac on the common carp Cyprinus carpio.

The nonsteroidal anti-inflammatory drug ketorolac is extensively used in the treatment of acute postoperative pain. This pharmaceutical has been found at concentrations of 0.2-60 µg/L in diverse water bodies around the world; however, its effects on aquatic organisms remain unknown. The present study, evaluated the oxidative stress and genotoxicity induced by sublethal concentrations of ketorolac (1 and 60 µg/L) on liver, brain, and blood of the common carp Cyprinus carpio. This toxicant induced oxidative damage (increased lipid peroxidation, hydroperoxide content, and protein carbonyl content) as well as changes in antioxidant status (superoxide dismutase, catalase, and glutathione peroxidase activity) in liver and brain of carp. In blood, ketorolac increased the frequency of micronuclei and is therefore genotoxic for the test species. The effects observed were time and concentration dependent. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1035-1043, 2016.

Factores asociados a displasia en mujeres con atipias de células escamosas de significado indeterminado / Dysplasia associated factors in women with squamous cell atypias of undetermined significance

Objetivo: identificar los factores asociados a displasia en mujeres que asisten al Hospital Central de la Policía Nacional o a diferentes dispensarios, cuya citología cérvicovaginal presentaba atipias de células escamosas de significado indeterminado (ASC-US).Materiales y métodos: estudio de prevalencia en el cual se identificaron los factores asociados a displasia de cuello uterino por medio de la correlación de las diferentes variables, por el servicio de Patología del Hospital Central de la Policía Nacional. Las diferentes variables fueron extraídas de las historias clínicas. Se realizó un reporte descriptivo de las prevalencias y se calcularon OR por medio de regresión logística para establecer la asociación entre las variables.Resultados: se encontraron porcentajes de distribución de displasia así: Sin displasia: 8.6%; Displasia leve: 80.2%; Displasia moderada: 8.2%; Displasia severa: 3.0%. La edad en la población tuvo una mediana de 47. 8 7 años. La población sin displasia fue de 8.6% y con displasia 91.4%. La asociación entre ciclos y displasia fue de 0.008 y entre antecedente personal de cáncer y displasia fue de 0.005. En la regresión logís-tica, la edad mostró asociación con una p<0.05.Conclusiones: la importancia de la toma de la citología cérvicovaginal cobra un papel cada vez más relevante en nuestra población, dado el aumento de la preva-lencia de displasia. Las principales recomendaciones son: adecuada toma de la citología y tener en cuenta la edad como factor importante para la asociación de displasia cérvicovaginal sobre los ASC-US, ya que en muchas ocasiones se pueden pasar por alto en la consulta diaria. Palabras clave: citología cérvicovaginal, asc-us, displasia

Objective: to identify factors associated with dysplasia in women attending the Central Hospital of the National Police or different clinics whose cervico-vaginal cyto-logy presented atypia squamous cell of undetermined significance (ASC-US).Materials and methods: prevalence study of what is intended to identify the factors associated with dysplasia of the cervix through the correlation of different variables, for the service of Pathology of the Central Hospital of the National Police. The variables were obtained through to medical records. It performs a report describing the prevalence's were calculated OR through logistic regression was used to establish the association between the variables.Results: the percentage of the distribution of dysplasia: Without dysplasia: 8.6%; Mild dysplasia: 80.2%; Moderate dysplasia: 8.2%; Severe dysplasia: 3.0%. The population has an average of 47 years. The percen-tage of people without dysplasia was 8.6% and 91.4% dysplasia. The analysis showed that divariado. The partnership between cycles and dysplasia was between 0,008 and personal history of cancer and dysplasia was 0005. For Multivariate logistic regression analysis age showed partnership with p <0.05.Conclusions: the importance of making the cervico-vaginal cytology charged an increasingly important role in our population, given the increased prevalence in dysplasia. Our main recommendation is, in addition to adequate and accurate making cytology, keep in mind that age is an important factor for the association cervico-vaginal dysplasia. And the ASC-US, as many times can be overlooked in the daily consultations. Key words: cervico-vaginal cytology, ASC-US dysplasia

Suppression of interleukin 1alpha and interleukin 1beta in human limbal epithelial cells cultured on the amniotic membrane stromal matrix.

AIMS: Amniotic membrane (AM) transplantation reduces inflammation in a variety of ocular surface disorders. The aim of this study was to determine if AM stroma suppresses the expression of the IL-1 gene family in cultured human corneal limbal epithelial cells. METHODS: Human corneal limbal epithelial cells were cultured from limbocorneal explants of donor eyes on plastic or on the AM stroma. Transcript expression of IL-1alpha, IL-1beta, IL-1 receptor antagonist (RA), and GAPDH was compared with or without addition of lipopolysaccharide to their serum-free media for 24 hours using RNAse protection assay (RPA). Their protein production in the supernatant was analysed by ELISA. RESULTS: Expression of IL-1alpha and IL-1beta transcripts and proteins was significantly reduced by cells cultured on the AM stromal matrix compared with plastic cultures whether lipopolysaccharide was added or not. Moreover, expression of IL-1 RA by cells cultured in the lipopolysaccharide-free medium was upregulated by AM stromal matrix. The ratio between IL-1 RA and IL-1alpha protein levels in AM cultures was higher than in plastic cultures. CONCLUSIONS: AM stromal matrix markedly suppresses lipopolysaccharide induced upregulation of both IL-1alpha and IL-1beta. These data may explain in part the effect of AM transplantation in reducing ocular surface inflammation, underscoring the unique feature of the AM as a substrate for tissue engineering.

Regulation of MMP-9 production by human corneal epithelial cells.

The matrix metalloproteinases, MMP-2 and MMP-9, are known to be critical extracellular-remodeling enzymes in wound healing and other diseases of the ocular surface. This study investigated the regulation of MMP-2 and MMP-9 in human corneal epithelial cells by growth factors and pro-inflammatory cytokines (IL-1beta and TNF-alpha) they are exposed to, and by doxycycline, a medication used to treat ocular surface disease. Primary human corneal epithelial cell cultures were treated with one of the following cytokines (IL-1alpha, IL-1beta, IL-6, IL-8, TNF-alpha) or growth factors (EGF, HGF, KGF, PDGF-BB, TGF-alpha, TGF-beta), with or without their corresponding inhibitors. The conditioned media were collected after 24 hr for gelatin zymography and MMP-9 activity assay. Total RNA was extracted from the cells treated for 6 hr and was subjected to RT-PCR and Northern hybridization. Between the two gelatinases, MMP-2 and MMP-9, detected by zymography, the 92 kDa MMP-9 in the conditioned medium was markedly up-regulated by the pro-inflammatory cytokines, IL-1beta and TNF-alpha. The MMP-9 protein and activity were dose-dependently stimulated by IL-1beta or TNF-alpha at 0.1, 1.0 and 10 ng ml(-1). This up-regulation was nearly abolished by neutralizing antibodies (IL-1beta and TNF-alpha) and by IL-1 receptor antagonist. Semi-quantitative RT-PCR and Northern hybridization disclosed that the MMP-9 transcript was also markedly up-regulated in a dose-dependent manner by IL-1beta and TNF-alpha. Doxycycline (10 microg ml(-1)) suppressed MMP-9 protein level and activity, but not its mRNA, that was stimulated by IL-1beta and TNF-alpha (1 ng ml(-1)). In contrast, the 72 kDa MMP-2 was not significantly modulated by any of these cytokines. In conclusion, production of MMP-9 is stimulated by the pro-inflammatory cytokines, IL-1beta and TNF-alpha. These factors may play a role in the pathogenesis of MMP-9 mediated corneal matrix degradation. The efficacy of doxycycline in treating ocular surface diseases may be related to its ability to suppress MMP-9 production in the corneal epithelium.

Doxycycline inhibition of interleukin-1 in the corneal epithelium.

PURPOSE: To evaluate the effect of doxycycline on the regulation of interleukin (IL)-1 expression and activity in human cultured corneal epithelium. METHODS: Human corneal limbal epithelium (HLE) was cultured from explants prepared from limbal rings of donor corneas. Primary cultured limbal epithelial cells were treated with either 10 microg/ml lipopolysaccharide (LPS), LPS with 10 microg/ml doxycycline, or LPS with 0.1 mg/ml methylprednisolone (MP) for 24 hours. The intracellular and supernatant protein amounts of IL-1alpha, the precursor and mature forms of IL-1beta, IL-1 receptor antagonist (IL-1 RA), and the intracellular level of IL-1beta-converting enzyme (ICE) were measured with enzyme-linked immunosorbent assays (ELISAs). Western blot analysis was performed to evaluate IL-1 RA protein. mRNA steady state amounts were determined by RNase protection assay (RPA) for IL-1alpha, IL-1beta, IL-1 RA, and ICE. RESULTS: LPS increased the mRNA and protein amounts of intracellular and released IL-1alpha, mature IL-1beta, and IL-1 RA. Doxycycline inhibited the LPS-induced IL-1beta increase in the mRNA and protein amounts in the corneal epithelium and upregulated the expression of the anti-inflammatory IL-1 RA protein. In addition, doxycycline reduced the steady state level of the cellular ICE protein but did not affect the level of ICE transcripts. IL-1beta secreted to the conditioned media of HLE was functionally active in inducing matrix metalloproteinase (MMP)-1 and MMP-3 in cultured corneal fibroblasts. Doxycycline significantly decreased IL-1beta bioactivity in the supernatants from LPS-treated corneal epithelial cultures. These effects were comparable to those induced by the corticosteroid, MP. CONCLUSIONS: Doxycycline can suppress the steady state amounts of mRNA and protein of IL-beta and decrease the bioactivity of this major inflammatory cytokine. These data may partially explain the clinically observed anti-inflammatory properties of doxycycline. The observation that doxycycline was equally potent as a corticosteroid, combined with the relative absence of adverse effects, makes it a potent drug for a wide spectrum of ocular surface inflammatory diseases.

The effects of experimental tear film removal on corneal surface regularity and barrier function.

PURPOSE: To evaluate corneal surface regularity and asymmetry, corneal thickness, barrier function, and contrast sensitivity after experimental removal of the precorneal tear layer. DESIGN: Prospective, clinic-based, nonrandomized (self-controlled) comparative trial. PARTICIPANTS: Six eyes of six healthy volunteers (three males, three females; age range, 29-40 years). METHODS: A precorneal tear lesion was created by pressing a sterile Biopore (Millipore, Bedford, MA) Teflon membrane against the central cornea. Corneal topography with both the Topographic Modeling System (TMS-1; Computed Anatomy, Tomey Technology, Cambridge, MA) and the Orbscan (Orbscan Inc., Salt Lake City, UT) were performed before the lesion was created and 30 seconds, 1 hour, and 4 hours after the lesion was created. Surface regularity and surface asymmetry indices were evaluated by the TMS-1 topography system. Maximum and minimum keratometric readings, corneal fluorescein staining, contrast sensitivity, and corneal thickness were evaluated before and after the tear lesion. Cytologic membranes were stained for MUC4 mucin using an indirect immunofluorescent staining technique. Confocal microscopy was performed to evaluate the integrity of the corneal epithelium in two eyes. Analysis of variance with polynomial contrasts was used to examine time trends of the outcome variables. MAIN OUTCOME MEASURES: The change in corneal surface regularity and asymmetry indices, corneal thickness, permeability to fluorescein dye, and contrast sensitivity before and after the lesion was made were compared. RESULTS: The corneal epithelium in the area of the lesion showed intense fluorescein staining 30 seconds postlesion but appeared normal by 4 hours. Confluent, homogeneous staining for MUC4 mucin was observed on the membranes used to create the lesion in all cases. The surface regularity index measured with the TMS-1 increased after the lesion was created and decreased toward normal by 4 hours (P = 0.017). Corneal thickness measured by the Orbscan instrument significantly increased in the central (P = 0.001), superior (P = 0.006), inferotemporal (P < 0.001) and superotemporal (P = 0.001) cornea immediately following the lesion and returned to normal by 4 hours. The lesion caused a decrease in visual acuity at 6.30%, 4% and 2.5% contrast sensitivities 1 hour postlesion and these measurements returned to prelesion values by 4 hours (P = 0.085, P = 0.005, P = 0.043). CONCLUSIONS: The precorneal tear layer serves as a permeability barrier and is essential for maintaining a smooth quality optical surface.

Regulation of MMP-9 activity in human tear fluid and corneal epithelial culture supernatant.

PURPOSE: To evaluate human corneal epithelial culture supernatant and tear fluid for the presence of activators and inhibitors of matrix metalloproteinase (MMP)-9, MMP-3, and tissue inhibitor of metalloproteinase (TIMP)-1, respectively, and to evaluate the effect of MMP-3 on the activation of MMP-9 in these specimens. METHODS: Unstimulated tear fluid was collected from patients with ocular rosacea and normal control subjects. Levels of MMP-9, MMP-3, and TIMP-1 were determined by enzyme-linked immunosorbent assay (ELISA) and/or immunoblot analysis. Supernatants from primary human corneal epithelial cultures and human tear fluid were incubated with MMP-3. Cultured epithelial cells and their supernatants were also treated with doxycycline before MMP-3 was added. Gelatin zymography was used to identify activated 82-kDa MMP-9. MMP-9 activity was assessed with a commercial MMP-9 activity assay system. RESULTS: MMP-9 and TIMP-1 were detected at significantly higher concentrations in rosacea-affected than in normal tear fluids. MMP-3 was detected exclusively in the tear fluid of patients with ocular rosacea who had corneal epithelial disease. Treatment of the supernatant and tear fluid with MMP-3 resulted in two bands with molecular weights of 92 kDa and 82 kDa, representing pro-MMP-9 and activated MMP-9, respectively. Doxycycline added to the conditioned media did not affect activation of MMP-9 by MMP-3. However, 24-hour treatment of corneal epithelial cultures with doxycycline resulted in a lower concentration and activity of MMP-9 in their supernatants. CONCLUSIONS: MMP-9 and TIMP-1 are produced by the human corneal epithelium and are present in tear fluid. MMP-3 alone is sufficient to activate MMP-9 on the ocular surface. Doxycycline does not directly inhibit this activation by MMP-3, but it decreases MMP-9 activity when added to corneal epithelial cultures.

Detection of sialomucin complex (MUC4) in human ocular surface epithelium and tear fluid.

PURPOSE: To evaluate human ocular surface epithelium and tear fluid for the presence of sialomucin complex (MUC4), a high-molecular-weight heterodimeric glycoprotein composed of mucin (ASGP-1) and transmembrane (ASGP-2) subunits. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis assays were used to identify sialomucin complex RNA in ocular surface epithelia. Immunoprecipitation and immunoblot analysis were used to identify immunoreactive species in human tears and in the corneal and conjunctival epithelia using antibodies specific for carbohydrate and peptide epitopes on the sialomucin complex subunits. Immunofluorescence staining was used to detect sialomucin complex in frozen sections and impression cytology specimens of human cornea and conjunctival epithelia. RESULTS: ASGP-1- and ASGP-2-specific sequences were amplified from RNA extracted from both conjunctival and corneal epithelial biopsies by RT-PCR. Sialomucin complex transcripts were also detected in these tissues by Northern blot analysis, with a greater level of RNA detected in the peripheral than the central corneal epithelium. Sialomucin complex was immunoprecipitated from tear fluid samples and both corneal and conjunctival epithelia and detected by immunoblot analysis with specific anti-ASGP-1 and anti-ASGP-2 antibodies. The ASGP-1 peptide antibody HA-1 stained the full thickness of the corneal and conjunctival epithelia. In contrast, antibody 15H10, which reacts against a carbohydrate epitope on ASGP-1, stained only the superficial epithelial layers of these tissues. No staining was observed in the conjunctival goblet cells. CONCLUSIONS: Sialomucin complex was originally identified in rat mammary adenocarcinoma cells and has recently been shown to be produced by the ocular surface epithelia of rats. Furthermore, it has been identified as the rat homologue of human MUC4 mucin. The present studies show that it is expressed in the stratified epithelium covering the surface of the human eye and is present in human tear fluid. Expression of a carbohydrate-dependent epitope on the mucin subunit (ASGP-1) of sialomucin complex occurs in a differentiation-dependent fashion. Sialomucin complex joins MUC1 as another membrane mucin produced by the human ocular surface epithelia but is also found in the tear fluid, presumably in a soluble form, as found on the rat ocular surface.

Tear fluid gelatinase B activity correlates with IL-1alpha concentration and fluorescein clearance in ocular rosacea.

PURPOSE: To correlate tear fluorescein clearance with interleukin-1alpha (IL-1alpha) concentration and gelatinase B (matrix metalloproteinase [MMP]-9) activity in the tear fluid of patients with ocular rosacea and normal control subjects. METHODS: Gelatinase activity was evaluated by gelatin zymography in tear fluid obtained from 13 patients with ocular rosacea (including 1 patient with recurrent epithelial erosion, 2 with recurrent peripheral corneal infiltrates and vascularization, and 2 patients with epithelial basement membrane dystrophy) and 13 normal subjects with normal aqueous tear production and no irritation symptoms. Tear fluorescein clearance was evaluated by measuring fluorescence in tear fluid collected from the inferior meniscus 15 minutes after instillation of 5 microl of 2% Na-fluorescein with a CytoFluor II fluorometer. Pro-MMP-9 and IL-1alpha concentrations in the tear fluid were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with normal control subjects, patients with ocular rosacea had a greater delay of tear fluorescein clearance (P < 0.001), a higher tear IL-1alpha concentration (P < 0.001), and a greater pro-gelatinase B (92 kDa) activity (P < 0.001) in their tear fluid. The 84-kDa active form of gelatinase B was observed in 46% of the rosacea tear samples and none of the controls. The zymographic results were confirmed by ELISA that showed a significantly greater concentration of pro-MMP-9 (92 kDa) in the tear fluid of rosacea patients than controls. Delayed tear clearance was correlated with elevated tear IL-1alpha concentration (p=0.67, P < 0.001) and increased tear gelatinase B activity (p=0.84, P < 0.001). Tear IL-1alpha concentration was correlated with tear gelatinase B activity (p=0.58, P < 0.002). CONCLUSIONS: Gelatinase B (MMP-9) activity is greater in patients with ocular rosacea than in normal eyes. The majority of this activity is due to 92-kDa proform of this enzyme. This activity is correlated with delayed tear clearance and tear fluid concentration of interleukin-1alpha, a proinflammatory cytokine that has been reported to stimulate gelatinase B production. Elevated gelatinase B activity in ocular rosacea may be involved in the pathogenesis of the irritation symptoms, recurrent epithelial erosions, vascularization, and epithelial basement membrane dystrophy that develops in the corneas of patients with this condition.

Altered cytokine balance in the tear fluid and conjunctiva of patients with Sjögren's syndrome keratoconjunctivitis sicca.

PURPOSE: To compare epidermal growth factor (EGF) concentration in tear fluid and levels of inflammatory cytokines in the conjunctival epithelium of patients with Sjögren's syndrome keratoconjunctivitis sicca with those of normal controls. METHODS: Schirmer 1 tear testing, corneal fluorescein staining and conjunctival impression cytology for quantitation of goblet cell density were performed in ten patients with Sjögren's syndrome-associated keratoconjunctivitis sicca and ten asymptomatic normal controls. ELISA was used to detect the concentration of EGF in tear fluid and interleukin 6 in lysates of conjunctival cytology specimens obtained from all subjects. The levels of RNA transcripts encoding inflammatory cytokines [interleukin 1alpha_(IL-1alpha), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor alpha_(TNF-alpha), and transforming growth factor beta1 (TGF-beta1)] as well as a housekeeping gene (G3PDH) were evaluated in conjunctival cytology specimens taken from all subjects by semiquantitative competitive reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Decreased tear fluid EGF concentration was noted in Sjögren's syndrome patients (mean 0.68 +/- 0.59 ng/ml) compared to controls (mean 1.66 +/- 0.45 ng/ml, P = 0.004). Significantly increased levels of IL-1alpha, IL-6, IL-8, TNF-alpha and TGF-beta1 RNA transcripts were found in the conjunctival epithelium of Sjögren's syndrome patients compared to controls (P < 0.05), while the level of G3PDH was similar in both groups. The concentration of IL-6 protein was significantly higher in Sjögren's syndrome conjunctiva samples (P = 0.012). Tear EGF concentration correlated with Schirmer 1 scores (rho 0.767, P < 0.001), corneal fluorescein staining scores (rho -0.562, P = 0.01), conjunctival goblet cell density (rho 0.661, P = 0.001) and the levels of IL-1alpha_and IL-8 RNA in the conjunctival epithelium (rho -0.677 and -0.747, respectively, P = 0.001). Both IL-1alpha_and IL-8 RNA in the conjunctival epithelium increased as Schirmer 1 scores decreased (P

Correlation of tear fluorescein clearance and Schirmer test scores with ocular irritation symptoms.

OBJECTIVE: To correlate and compare the Schirmer 1 test and a new method of measuring tear fluorescein clearance with the CytoFluor II fluorometer with the severity of ocular irritation symptoms, clinical signs of meibomian gland disease, corneal fluorescein staining scores, and corneal and conjunctival sensitivity. DESIGN: Case-control study. PARTICIPANTS: Forty patients presenting with a chief complaint of ocular irritation, and 40 asymptomatic control subjects of similar age distribution. INTERVENTION: All subjects completed a symptom questionnaire, a baseline ocular examination, fluorescein clearance test (FCT), and Schirmer 1 test. MAIN OUTCOME MEASURES: The FCT was performed with a CytoFluor II fluorophotometer by measuring the fluorescein concentration in minimally stimulated tear samples collected from the inferior tear meniscus 15 minutes after instillation of 5 microl of 2% sodium fluorescein. Severity of ocular irritation was assessed with a symptom questionnaire. Schirmer 1 test, biomicroscopic meibomian gland evaluation, corneal fluorescein staining score, and corneal and conjunctival sensation scores were assessed with the Cachet-Bonnet anesthesiometer in all subjects. RESULTS: Irritation symptoms correlated with higher log tear fluorescein concentration (symptomatic 3.08 +/- 0.62 units/,microl, normal control 1.89 +/- 0.7 units/microl, P < 0.005) and lower Schirmer 1 test scores (symptomatic 12.6 mm, normal control 22.3 mm, P < 0.005). The FCT showed greater predictive value for identifying ocular irritation than the Schirmer 1 test. A fluorescein concentration of 274 units//microl eliminated 80% of the normal subjects (specificity) and identified 85% of the abnormal subjects (sensitivity). Log of tear fluorescein concentration and the Schirmer 1 test correlated with meibomian gland orifice metaplasia (2.81 +/- 0.78 units/microl and 14.47 +/- 9.53 mm in those with metaplasia vs. 1.83 +/- 0.71 units/microl and 23.14 +/- 7.67 mm in those without metaplasia, P < 0.001) and with the percentage of acinar dropout. Both log of tear fluorescein concentration and the Schirmer 1 test correlated with corneal fluorescein staining (Pearson correlation of 0.394 P < 0.0001 for Schirmer 1 test and 0.312 P < 0.005 for log of tear fluorescein). In addition, log of tear fluorescein and Schirmer 1 test scores correlated with corneal and conjunctival sensation scores (Spearman's rho for corneal sensation: log of tear fluorescein -0.38, P < 0.003, Schirmer 1 test -0.39, P < 0.002, and for conjunctival sensation: log of tear fluorescein -0.391, P < 0.001, Schirmer 1 test -0.23, P < 0.061). CONCLUSIONS: The FCT shows a greater predictive value for ocular irritation than the Schirmer 1 test. It correlates better with age, meibomian gland dysfunction, and decreased corneal and conjunctival sensation. Decreased tear clearance was identified as a risk factor for ocular irritation, even in subjects with normal Schirmer scores. This simple technique may provide new clues into the mechanism and therapy of ocular irritation.

The prevalence of musculoskeletal complaints among women in Tijuana, Mexico: sociodemographic and occupational risk factors.

The authors interviewed an age- and occupation-stratified sample of 466 women, aged 18-40, from 12 Tijuana neighborhoods, about sociodemographic characteristics, work and reproductive history, and musculoskeletal complaints. A total of 29.8% reported experiencing aches or pain in the low back, 38.3% in the upper back, 26.4% in the neck/shoulders, 18.2% in the hand/wrist, and 28.3% in the legs in the preceding year. Both sociodemographic and occupational factors were associated with these complaints. Very low educational attainment, having substandard housing, being the head of household, and being a migrant were each associated with an increased prevalence of one or more musculoskeletal complaints. In general, working outside the home increased the risk of musculoskeletal complaints. Compared with women who had not worked in the preceding 30-month period, those working in the maquiladora had 40-90% higher risks of upper back, neck/shoulder, and hand/wrist pain. Compared with women working outside the maquiladora, maquiladora women workers had 20% higher risks of low back, upper back, and neck/shoulder complaints. More detailed studies of the incidences of musculoskeletal disorders and of specific etiologic risk factors within the maquiladora industry are warranted. Future studies should concurrently evaluate sociodemographic risk factors.

Prevalence of back discomfort and estimates of back load in two manufacturing facilities.

This study evaluated the association between the prevalence of back discomfort and estimates of back load posed by nine jobs in two manufacturing facilities. Prevalence of back discomfort experienced was estimated through self-administered questionnaires. A total of 266 questionnaires were distributed to workers randomly selected from nine jobs in two factories. Workers were asked to rate on a 0-5 scale the discomfort level they experienced in the back for a one-month period before and at the time of the survey. The return rate for each job ranges from 57% to 100%. Overall, 14.5% of the survey respondents experienced some discomfort in the back. With the assistance of a checklist, nine supervisors rated each task of the job they supervised by the magnitude of the force (low, moderate, or high) and by the duration, (less than 30% time, 30% to 50% time, and greater than 50% time) that workers typically spent in awkward back postures, such as back flexion, extension, twisting, and lateral bending. An additional total back load estimate was provided independently by an ergonomist. Logistic regression analysis found a positive association between the back discomfort prevalence observed in the present study and the load estimates both by the ergonomist and by task information based on back twisting. Significant concordance was found between the ergonomist's load estimates and the supervisors' estimate of the duration of twisted back. This study demonstrated not only that a checklist approach could provide useful task information for deriving exposure estimates, but also that exposure estimate for a job could be derived from its constituent tasks. Though in this study it was the supervisor who utilized the checklist to estimate the back loads, there is no reason why experienced workers could not use the checklist to provide similar estimates. A large-scale study should be conducted to improve the design of this checklist approach.

Cytokines and tear function in ocular surface disease.

In summary, tear EGF levels correlate most strongly with tear production in normals, and it is likely that some form of homeostatic mechanism exists to provide a constant supply to the ocular surface. Commercial ELISA kits appear to measure EGF in tears with good consistency and may be useful in the future to improve comparability of data from different studies. In addition, in ocular rosacea, which mimics keratoconjunctivitis sicca in a number of respects, there is a differential increase in the level of the inflammatory cytokine IL-1 alpha in the tear fluid. Much of this elevation appears to be the result of reduced tear turnover, which may form an important positive feedback mechanism encouraging tear stagnation and the perpetuation of ocular surface inflammation.

Alterations of ocular surface gene expression in Sjögren's syndrome.

We have demonstrated that conjunctival epithelium of SS patients displays increased numbers of S-phase cells compared with non-dry eye controls. Moreover, in SS patients, these S-phase cells are distributed throughout all strata of the epithelium. The expression of MUC-1, a cell surface marker indicative of terminally differentiated epithelium, is localized to the conjunctival epithelial surface in SS and control patients. However, MUC-1 surface immunoreactivity appears to be reduced in SS epithelium, suggesting disruption of normal epithelial differentiation. A MUC-1 epitope exposed by pretreatment with neuraminidase is expressed in the basal and suprabasal layers of both patient populations. This antigen likely represents nascent, partially processed MUC-1(6) and may serve as a marker of the preterminally differentiated epithelial phenotype. Messenger RNA encoding several different inflammatory cytokines, including TNF-alpha, IL-1 alpha and beta, IL-6, IL-8, IL-10, and TGF-beta 1, is expressed at elevated levels within the conjunctival epithelium of SS patients compared with non-dry eye controls. Based on these observations, we have formulated a model to explain the ocular surface pathology of Sjögren's syndrome. We hypothesize that mechanical abrasion secondary to aqueous tear deficiency creates an inflammatory environment where conjunctival epithelial cells and lymphocytes are stimulated to produce and secrete various cytokines (i.e., IL-1, TNF-alpha, IL-6, IL-8, etc.) into the tear film. Elevated cytokine levels within the tear film, perhaps combined with reduced concentrations of essential lacrimal gland-derived factors (i.e., EGF, retinol), create an environment in which terminal differentiation of the ocular surface epithelium is impaired. As a consequence, the epithelium becomes hyperplastic, displaying increased mitotic activity, and loses the ability to express mature protective surface molecules including the membrane-bound mucin, MUC-1. This would imply that anti-inflammatory medications (i.e., corticosteroids or cyclosporine) that suppress the inflammatory component of this cascade may ameliorate the ocular surface disease and discomfort experienced by SS patients.

Inflammatory cytokines in the tears of patients with ocular rosacea.

OBJECTIVE: The purpose of the study is to compare tear fluid concentrations of interleukin-1alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), and epidermal growth factor (EGF) in ocular rosacea with those in control subjects and to examine the relation between tear functions, such as production and clearance rate, and the concentrations of cytokines in tear fluid. PARTICIPANTS AND INTERVENTION: Fourteen patients with severe meibomian gland disease, facial rosacea, and symptoms of ocular irritation were examined for ocular surface disease, tear production, and tear clearance rate (TCR). Twelve control subjects, frequency-matched for age, and 15 ideal normal subjects with no ocular symptoms and normal tear function were assessed using the same parameters. Minimally stimulated tear samples (20 microl) were drawn from each subject and analyzed using a sandwich enzyme-linked immunosorbent assay to detect IL-1alpha, TNF-alpha, and EGF. RESULTS: Tear IL-1alpha concentration was significantly higher in patients with rosacea than in age-matched (P = 0.003) and ideal control subjects (P < 0.001). Tumor necrosis factor-alpha was not detected in patients or control subjects, indicating levels of less than 10 pg/ml. Epidermal growth factor was not significantly higher in patients with rosacea than in age-matched control subjects. Tear turnover LN(TCR) was lower in patients with rosacea than in both age-matched (P = 0.048) and ideal control subjects (P = 0.002). Schirmer I scores were statistically lower in patients with rosacea than in ideal control subjects (P = 0.013), but not age-matched control subjects. Interleukin-1alpha was correlated inversely with LN(TCR) (r= -0.58, P < 0.0001) and Schirmer I (r = -0.39, P = 0.012). CONCLUSIONS: Concentrations of IL-1alpha are present in normal tears but are elevated in ocular rosacea, whereas TNF-alpha is not present in either case. The reduced tear turnover, LN(TCR), its inverse correlation with IL-1alpha, and the absence of TNF-alpha in the tears of these patients suggest that the increased concentration of IL-1alpha observed may be largely because of clearance failure of cytokine normally produced at the ocular surface.

The effects of age, gender, and fluid dynamics on the concentration of tear film epidermal growth factor.

PURPOSE: To identify the relationship between epidermal growth factor (EGF) concentration in human tears and clinical tear-flow parameters and how these vary with age and gender. METHODS: Tear samples were collected with minimal stimulation from 68 healthy and asymptomatic adults (33 men, 35 women), aged 21-88 years. EGF concentrations were determined by sandwich enzyme-linked immunosorbent assay (ELISA) in 65 cases. Schirmer tests were performed without anesthesia, and the clearance of fluorescein from the tear film assessed. The Tear Function Index (TFI) was calculated from these values. RESULTS: There were approximately equal numbers of male and female subjects with a similar age distribution for each gender (48 +/- 3 and 51 +/- 3 years, mean +/- SEM, respectively). Ninety percent of tear EGF concentrations were between 0.75 and 7.1 ng/ml. Tear EGF level correlated significantly with Schirmer I value, but not with age. Schirmer I value correlated with tear clearance [LN(TCR)] but not with age. Tear EGF concentrations were significantly higher for men (3.4 +/- 0.3 ng/ml) than for women (2.4 +/- 0.3 ng/ml; p = 0.043). CONCLUSIONS: EGF concentrations is tear samples from normal humans were found to correlate with gender and Schirmer I value but not with tear clearance.

A novel method of tear collection: comparison of glass capillary micropipettes with porous polyester rods.

PURPOSE: To develop a rapid, user-friendly method of tear collection to facilitate tear-protein analysis. METHODS: Tears were collected from a total of 19 normal volunteers without evidence of ocular-surface disease with either porous polyester rods or glass-capillary micropipettes. Tear-collection rate and recovery of two tear proteins, epidermal growth factor (EGF, low abundance) and lactoferrin (LFR, high abundance) were compared between polyester rods and glass-capillary micropipettes. The recovery of LFR and EGF and the stability of these proteins after storage at -70 degrees C were quantitated by specific monoclonal enzyme-linked immunosorbent assay (ELISA). RESULTS: Polyester rods collected tears an average of 3.9-fold faster than glass-capillary micropipettes (p < 0.001). Both methods were comparable in efficacy of protein recovery. The polyester rods demonstrated a trend toward enhanced recovery, but this difference was not statistically significant (p = 0.12, LFR; p = 0.055, EGF). Analysis of the reliability and reproducibility of the tear-collection assay system revealed that ELISA analysis is highly reproducible, but there is significant day-to-day variation in tear-protein levels of both LFR and EGF for a given volunteer. Both LFR and EGF displayed a trend toward enhanced detection by ELISA shortly after freezing at -70 degrees C and slow decay after storage at -70 degrees C for up to 72 and 105 days, respectively. After stimulation of reflex tearing via the nasolacrimal reflex, LFR levels remained relatively constant, whereas EGF levels for most patients declined and then plateaued. CONCLUSIONS: Polyester rods provide a more rapid, user-friendly alternative to glass-capillary micropipettes for the collection and analysis of tear fluid and tear proteins. Polyester rods may have greater clinical utility, facilitating routine analysis of the preocular tear film.