Influence of sex on chronic steroid-induced glaucoma: 24-Weeks follow-up study in rats.

The objective was to evaluate ocular changes based on sex in steroid-induced glaucoma models in rats comparing healthy controls, over 24 weeks follow-up. Eighty-nine Long-Evans rats (38 males and 51 females) with steroid-induced glaucoma were analysed. Two steroid-induced glaucoma models were generated by injecting poly-co-lactic-glycolic acid microspheres loaded with dexamethasone (MMDEX model) and dexamethasone-fibronectin (MMDEXAFIBRO model) into the ocular anterior chamber. Intraocular pressure was measured by rebound tonometer Tonolab®. Neuroretinal function was analysed using dark- and light-adapted electroretinography (Roland consult® RETIanimal ERG), and structure was analysed using optical coherence tomography (OCT Spectralis, Heidelberg® Engineering) using Retina Posterior Pole, Retinal Nerve Fibre Layer and Ganglion Cell Layer protocols over 24 weeks. Males showed statistically (p < 0.05) higher intraocular pressure measurements. In both sexes and models neuroretinal thickness tended to decrease over time. In the MMDEX model, males showed higher IOP values and greatest percentage thickness loss in the Ganglion Cell Layer (p = 0.015). Females receiving MMDEXAFIBRO experienced large fluctuations in thickness, a higher percentage loss (on average) in Retina Posterior Pole (p = 0.035), Retinal Nerve Fibre Layer and Ganglion Cell Layer than aged-matched males, and the highest thickness loss rate by mmHg. Although no difference was found by sex in dark- and light-adapted electroretinography, increased amplitude in photopic negative response was found in MMDEX males and MMDEXAFIBRO females at 12 weeks. Although both glaucoma models used dexamethasone, different intraocular pressure and neuroretinal changes were observed depending on sex and other influential cofactors (fibronectin). Both sex and the induced glaucoma model influenced neuroretinal degeneration.

Stargardt's pigmentosa: A novel combination of two inherited retinal dystrophies.

60-year-old woman referring visual disability. She presented bone spicule pigmentation and retinal atrophy in all peripheral retina, as well as macular retinal flecks. Multimodal imaging showed typical findings of both inherited retinal dystrophies (IRD). Electroretinogram confirmed rod dysfunction. Biallelic mutations were found in ABCA4 and CNGA1 genes. Although not common, different IRDs may be present in a same patient at the same time. This is the first reported case of the combination of RP with late-onset Stargardt's disease. We propose the name 'Stargardt's pigmentosa' for this novel clinical entity.

Hemorragia retrobulbar espontánea asociada a consumo de anticoagulantes / Spontaneous retrobulbar haemorrhage associated with anticoagulants

La hemorragia retrobulbar es un sangrado en la región intraorbitaria retroseptal que genera un síndrome compartimental orbitario. Se presenta el caso de una mujer de 86 años que acudió a Urgencias por dolor ocular y pérdida de visión en ojo izquierdo de seis horas de evolución. Presentaba tratamiento anticoagulante con 300 mg/día de Dabigatrán por fibrilación auricular como único antecedente médico. La exploración clínica fue compatible con hemorragia retrobulbar, diagnóstico confirmado por TAC urgente, realizándose de forma inmediata una cantotomía con cantolisis. Se realizó RMN orbitaria que descartó la existencia de malformaciones arteriovenosas como factor desencadenante, diagnosticándose de hemorragia retrobulbar espontánea asociada a consumo de anticoagulantes. La singularidad de este caso radica en formar parte del pequeño porcentaje de hemorragias retrobulbares que no se asocian a causa traumática ni postquirúrgica así como en ilustrar una localización muy poco frecuente de sangrado asociado a anticoagulación.(AU)

Retrobulbar hemorrhage consists of bleeding in the retroseptal intraorbital region generating an orbital compartment syndrome. We present the case of an 86-year-old woman who came to the Emergency Room due to ocular pain and loss of vision in the left eye of six hours of evolution. The only medical history was atrial fibrillation on anticoagulant treatment with Dabigatran 300mg daily. The clinical examination was compatible with retrobulbar hemorrhage and the urgent CT confirmed the diagnosis, performing immediately after a canthotomy with cantolysis. In the absence of triggering factors, an orbital MRI was performed which ruled out the existence of arteriovenous malformations, diagnosing spontaneous retrobulbar hemorrhage associated with the use of anticoagulants. The uniqueness of this case is that it forms part of the small percentage of retrobulbar hemorrhages that are not associated with trauma or postsurgical causes, as well as in illustrating a very rare location of bleeding associated with anticoagulation.(AU)

[Spontaneous retrobulbar haemorrhage associated with anticoagulants].

Retrobulbar hemorrhage consists of bleeding in the retroseptal intraorbital region generating an orbital compartment syndrome. We present the case of an 86-year-old woman who came to the Emergency Room due to ocular pain and loss of vision in the left eye of six hours of evolution. The only medical history was atrial fibrillation on anticoagulant treatment with Dabigatran 300mg daily. The clinical examination was compatible with retrobulbar hemorrhage and the urgent CT confirmed the diagnosis, performing immediately after a canthotomy with cantolysis. In the absence of triggering factors, an orbital MRI was performed which ruled out the existence of arteriovenous malformations, diagnosing spontaneous retrobulbar hemorrhage associated with the use of anticoagulants. The uniqueness of this case is that it forms part of the small percentage of retrobulbar hemorrhages that are not associated with trauma or postsurgical causes, as well as in illustrating a very rare location of bleeding associated with anticoagulation.

Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres.

PURPOSE: To evaluate a new chronic glaucoma model produced by intracameral injection of dexamethasone-loaded poly lactic-co-glycolic acid microspheres (Dex-PLGA-Ms) over six months. METHODS: Healthy rats received two injections (at baseline and Week 4) of Dex-PLGA-Ms into the anterior chamber of the right eye. Clinical signs and intraocular pressure (IOP) were weekly recorded. The structure of the retina and optic nerve was in vivo evaluated using optical coherence tomography (OCT) every two weeks and functionally using dark- and light-adapted electroretinography at 0-12-24 weeks. Histological studies were also performed. RESULTS: IOP progressively increased up to hypertension (23.22 ± 3.63 mmHg) in both eyes but did so later in left eyes. OCT quantified a decrease in full-thickness retina posterior pole (R), retinal-nerve-fiber layer (RNFL), and ganglion-cell layer (GCL) thickness up to 24 weeks. Right eyes showed higher neuroretinal thickness loss up to week 8. RNFL experienced the highest percentage thickness loss at the inferior-superior axis, while in GCL the inner sectors of the horizontal axis (Nasal-Temporal) suffered the greatest decrease in thickness. Retinal ganglion cell, photoreceptor, and intermediate cell functionality decreased over time. Increased deposition of collagen IV was also found in zonular fibers and the ciliary body. CONCLUSIONS: This work shows the usefulness of drug delivery systems, not to treat pathology but to induce it. Only two injections of Dex-PLGA-Ms in the anterior chamber of rat eyes were enough to progressively create ocular hypertension and subsequent functional and structural neuroretinal degeneration, at least over 6 months.

Brimonidine-LAPONITE® intravitreal formulation has an ocular hypotensive and neuroprotective effect throughout 6 months of follow-up in a glaucoma animal model.

Intravitreal administration is widely used in ophthalmological practice to maintain therapeutic drug levels near the neuroretina and because drug delivery systems are necessary to avoid reinjections and sight-threatening side effects. However, currently there is no intravitreal treatment for glaucoma. The brimonidine-LAPONITE® formulation was created with the aim of treating glaucoma for extended periods with a single intravitreal injection. Glaucoma was induced by producing ocular hypertension in two rat cohorts: [BRI-LAP] and [non-bri], with and without treatment, respectively. Eyes treated with brimonidine-LAPONITE® showed lower ocular pressure levels up to week 8 (p < 0.001), functional neuroprotection explored by scotopic and photopic negative response electroretinography (p = 0.042), and structural protection of the retina, retinal nerve fibre layer and ganglion cell layer (p = 0.038), especially on the superior-inferior axis explored by optical coherence tomography, which was corroborated by a higher retinal ganglion cell count (p = 0.040) using immunohistochemistry (Brn3a antibody) up to the end of the study (week 24). Furthermore, delayed neuroprotection was detected in the contralateral eye. Brimonidine was detected in treated rat eyes for up to 6 months. Brimonidine-LAPONITE® seems to be a potential sustained-delivery intravitreal drug for glaucoma treatment.

Espacio libre de humo de tabaco. Efecto su implementación en una Unidad Médico Familiar Número 2 - México / Smoke - free space of tobacco. Effect of its implementation in the Unidad Médico Familiar 2 - México

El tabaquismo es un problema de Salud Pública global, que afecta directamente la salud del fumador y pasivamente a las personas que lo rodean. La Organización Mundial de la Salud ha recomendado la aplicación de medidas de control para su consumo, comercialización y publicidad. Se realizó un estudio cuasi-experimental con la implementación de un programa educativo basado en las líneas estratégicas del programa Espacio Libre de Humo de Tabaco, en 224 adultos, (124 usuarios y 100 trabajadores) de la Unidad Médico Familiar, además se evaluó el conocimiento acerca del tabaco mediante algunos cuestionaros oficiales del Manual de Ambientes Laborales Libres de Humo de Tabaco previo a la intervención educativa y posterior a esta. La intervención educativa se dividió en 5 pasos, en los cuales se capacitó y orientó a la población acerca del tabaquismo, informando sobre las consecuencias, daños a la salud, tratamientos entre otros temas, en sesiones de 60 minutos para grupos de 3 a 5 asistentes. Previo a la intervención el 16,9% de usuarios y 18% de trabajadores eran fumadores, posterior a esta el consumo se redujo a 14,5% (p= 0,250) y 16 % (p=0,500) respectivamente sin encontrar diferencias significativas, sin embargo la implementación del programa mejoró el nivel de conocimientos sobre el programa Espacio Libre de Humo de Tabaco (p=0,008) (p=0,005), además ayudó a que la población identifique los efectos dañinos del tabaco

Smoking is a global public health problem, which directly affects the health of the smokers and passively the people around them. The World Health Organization has recommended the implementation of control measures for its consumption, marketing and advertising. A quasi-experimental study was conducted on the implementation of an educational program based on the strategic lines of the Tobacco Smoke Free Space in 224 adults (124 users and 100 workers) of the Family Medical Unit, in addition to knowledge about tobacco through some questions of the Manual of smoke-free prior to and after educational intervention. The educational intervention was divided into 5 steps, in which the population was trained and guided about smoking, informing about the consequences, damage to health, treatments among other topics, in 60-minute sessions for groups of 3 to 5 attendees. Prior to the intervention, 16, 9% of users and 18% of workers were smokers, after this educational intervention the percentage was reduced to 14, 5% (p=0,250) and 16% (p=0,500) respectively without finding significant differences, however the implementation of the program improved the level of knowledge on the policy of the Tobacco Smoke-Free Space (p=0,008) (p=0,005), also helped adults identify the harmful effects of tobacco

The anti-thrombotic effects of vitamin D and their possible relationship with antiphospholipid syndrome.

The importance of the immunomodulatory effects of vitamin D has recently been associated with autoimmune and chronic inflammatory diseases. Vitamin D deficiency has been linked to the development of autoimmune conditions. Antiphospholipid syndrome is an autoimmune disease characterized by thrombotic events and obstetric complications in patients with antiphospholipid antibodies. Current data show that patients with antiphospholipid syndrome have a high prevalence of vitamin D deficiency even without classic risk factors. Several studies have suggested vitamin D may have anti-thrombotic functions. In antiphospholipid syndrome, low vitamin D serum levels have been associated with thrombotic manifestations, suggesting a possible protective role of vitamin D in antiphospholipid syndrome. This literature review presents current evidence on the haemostatic functions of vitamin D and their possible relationship with the clinical manifestations of antiphospholipid syndrome.

Factors of the epidemiological triad that influence the persistence of human papilloma virus infection in women with systemic lupus erythematosus.

We studied the epidemiologic triad-related factors influencing human papilloma virus (HPV) persistence in Mexican women with systemic lupus erythematosus (SLE). Patients aged ≥18 years with SLE (American College of Rheumatology criteria), with and without HPV persistence, were selected. Groups were analyzed by (1) host: clinical disease characteristics; (2) agent: (I) infectious (prevalence, incidence, HPV genotype and co-infections (≥2 HPV genotypes or mycoplasmas)), (II) chemical (contraceptives and immunosuppressive drugs) and (III) physical (vitamin D deficiency) and (3) environment. A total of 121 SLE patients were selected over a two-year period. (1) Host: mean age 45.8 years and disease duration 12.7 years. (2) Agent: (I) infectious. HPV infection prevalence in the second sample was 26.4%, high-risk HPV genotypes 21.5% and co-infections 7.4%. HPV infection incidence was 13.2%, persistence 13.2% and clearance 15.7%. (II) Chemical: use of oral hormonal contraceptives 5% and immunosuppressive treatment 97.5%. (III) Physical: Vitamin D levels were similar in both groups. (3) Environment: (I) natural. A total of 60.6% of patients were residents of Puebla City. (II) Social: The mean education level was 10.9. Poverty levels were: III degree 52.4%, IV degree 28% and II degree 17%. (III) Cultural behavioral: Onset of sexual life was 20.5 years, 10% had ≥3 sexual partners and 51.2% were postmenopausal. In conclusion, no factor of the epidemiologic triad was associated with HPV infection prevalence.

Prevalence of functional gastrointestinal disorders in adults with systemic lupus erythematosus.

Objective (a) to assess the prevalence of functional gastrointestinal disorders (FGIDs) in female Mexican systemic lupus erythematosus (SLE) patients using the Rome III criteria and (b) to examine the effect of disease duration on FGID prevalence. Methods Female SLE outpatients aged ≥18 years with no organic gastrointestinal disorder were included. Participants were invited to upper gastrointestinal endoscopy screening and a faecal immunochemical test. FGID symptoms were evaluated using the Rome III questionnaire. Results Eighty-six SLE patients with median age of 45 (interquartile range 34-54) years were included. At least one FGID was found in 76.7% (66/88) of patients with SLE. The most prevalent domains of FGID diagnosed were functional oesophageal, gastroduodenal disorders and bowel disorders, of which functional dyspepsia (72.7%), functional heartburn (68.1%) and bloating (63.8%) were the most frequent. Fifty-nine per cent of patients had overlapping FGIDs. The most prevalent overlap was the combination of functional dyspepsia and functional heartburn. Patients with longer disease duration had a higher prevalence of FGID than those with shorter disease duration. Conclusions There was a high prevalence of FGIDs in Mexican SLE women with low disease activity. Overlapping FGIDs were frequent. Longer disease duration may be associated with FGIDs in SLE patients.

Factors Associated with Health-Related Quality of Life in Mexican Lupus Patients Using the LupusQol.

INTRODUCTION: Health-related quality of life (HRQOL) is affected by numerous clinical variables, including disease activity, damage, fibromyalgia, depression and anxiety. However, these associations have not yet been described in Mexican patients with systemic lupus erythematosus (SLE). OBJECTIVE: To evaluate the relationship between disease activity, damage, depression and fibromyalgia and HRQOL measured by the LupusQoL-instrument in Mexican patients with SLE. METHODS: A cross-sectional study was conducted in women fulfilling the 1997 ACR classification criteria for SLE. HRQOL was evaluated using a disease-specific instrument for SLE, the LupusQoL (validated for the Spanish-speaking population). Patients were evaluated clinically to determine the degree of disease activity and damage using the Mexican Systemic Lupus Erythematosus Disease Activity Index (Mex-SLEDAI) and Systemic Lupus International Collaborating Clinics-Damage Index (SLICC), respectively. Fibromyalgia and depression were assessed using the ACR criteria and the CES-D scale, respectively. The relationship between HRQOL and these variables was measured using Spearman's rank correlation coefficient and linear regression analysis. RESULTS: A total of 138 women with SLE, age 40.3±11 years, disease duration 8.8±6.4 years, with disease activity in 51.4%, depression in 50%, damage in 43% and fibromyalgia in 19.6% were included. Poorer HRQOL correlated with depression (r = -0.61; p< 0.005), fibromyalgia (r = -0.42; p< 0.005), disease activity (r = -0.37; p < 0.005) and damage (r = -0.31; p < 0.005). In the multivariate linear regression analysis, damage (ß = -3.756, p<0.005), fibromyalgia (ß = -0.920, p<0.005), depression (ß = -0.911, p<0.005) and disease activity (ß = -0.911, p<0.005) were associated with poor HRQOL. CONCLUSION: SLE disease activity, damage, fibromyalgia and depression were associated with poor HRQOL in our sample of Mexican SLE patients.

Incidence of cervical human papillomavirus infection in systemic lupus erythematosus women.

Objectives Our objective was to study the incidence, persistence and clearance of human papillomavirus infection in systemic lupus erythematosus women and assess risk factors for persistence of human papillomavirus infection. Methods We carried out a prospective, observational cohort study of 127 systemic lupus erythematosus women. Patients were evaluated at baseline and at three years. Traditional and systemic lupus erythematosus women-related disease risk factors were collected. Gynaecological evaluations and cervical cytology screening were made. Human papillomavirus detection and genotyping were made by polymerase chain reaction and linear array. Results The cumulative prevalence of human papillomavirus infection increased from 22.8% at baseline to 33.8% at three years; p = < 0.001: 20.1% of patients experienced 43 incident infections. The risk of any human papillomavirus infection was 10.1 per 1000 patient-months. At three years, 47 (88.6%) prevalent infections were cleared. Independent risk factors associated with incident human papillomavirus infection included more lifetime sexual partners (odds ratio = 1.8, 95% confidence interval = 1.11-3.0) and cumulative cyclophosphamide dose (odds ratio = 3.9, 95% confidence interval = 1.2-12.8). Conclusions In systemic lupus erythematosus women, the cumulative prevalence of human papillomavirus infection, including high risk-human papillomavirus and multiple human papillomavirus infections, may increase over time. Most persistent infections were low risk-human papillomavirus. The number of lifetime sexual partners and the cumulative cyclophosphamide dose were independently associated with incident human papillomavirus infection.

The role of infectious diseases in the catastrophic antiphospholipid syndrome.

Catastrophic antiphospholipid syndrome (CAPS), also called "Asherson syndrome", is a variant of the antiphospholipid syndrome (APS) that occurs in less than 1% of APS cases. The etiology of CAPS is uncertain; however, several triggering factors have been recognized. The most common of these are infectious diseases, particularly those of the respiratory tract. CAPS pathogenesis is incompletely understood, but several theories have been proposed, such as the molecular mimicry theory, which describes the production of anti-ß2-glycoprotein I (GP1) antibody in response to infection. The process is complex and involves the activation of Toll-like receptor 4 (TLR-4), which triggers a cytokine storm, followed by endothelial alterations that induce a procoagulant state.

Socioeconomic status and organ damage in Mexican systemic lupus erythematosus women.

The objective of this cross-sectional study was to determine relationships between socioeconomic status and organ damage in Mexican systemic lupus erythematosus (SLE) patients. Demographic and clinical variables were assessed. Socioeconomic status was evaluated using the Graffar method and monthly household income. Lupus activity and organ damage were measured using the SLE disease activity scale, validated for the Mexican population (Mex-SLEDAI), and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) scale. The 143 Mexican female SLE patients included (mean age 40.1 ± 8.9 years, mean disease duration 8.9 ± 6.3 years) had a mean monthly household income of $ 407.2 ± 326.5. According to the Graffar index, 18.9%, 52.5%, and 28.7% had high/medium-high, medium, and medium-low/low socioeconomic status, respectively. Organ damage was observed in 61 patients (42.7%). Patients with organ damage had lower monthly household incomes ($241.4 ± 152.4 vs. $354.8 ± 288.3) and were more frequently unemployed (57.3% vs. 35.3%; p = 0.01) than those without. Low monthly income was not associated with lupus activity or self-reported health status. In the adjusted multivariate analysis, low monthly income ( < $300) was associated with organ damage. In conclusion, low income may be associated with organ damage in Mexican SLE patients.

P-glycoprotein in autoimmune rheumatic diseases.

P-glycoprotein (Pgp) is a transmembrane protein of 170 kD encoded by the multidrug resistance 1 (MDR-1) gene, localized on chromosome 7. More than 50 polymorphisms of the MDR-1 gene have been described; a subset of these has been shown to play a pathophysiological role in the development of inflammatory bowel disease, femoral head osteonecrosis induced by steroids, lung cancer and renal epithelial tumors. Polymorphisms that have a protective effect on the development of conditions such as Parkinson disease have also been identified. P-glycoprotein belongs to the adenosine triphosphate binding cassette transporter superfamily and its structure comprises a chain of approximately 1280 aminoacid residues with an N-C terminal structure, arranged as 2 homologous halves, each of which has 6 transmembrane segments, with a total of 12 segments with 2 cytoplasmic nucleotide binding domains. Many cytokines like interleukin 2 and tumor necrosis factor alpha increase Pgp expression and activity. Pgp functions as an efflux pump for a variety of toxins in order to protect particular organs and tissues as the central nervous system. Pgp transports a variety of substrates including glucocorticoids while other drugs such as tacrolimus and cyclosporine A act as modulators of this protein. The most widely used method to measure Pgp activity is flow cytometry using naturally fluorescent substrates such as anthracyclines or rhodamine 123. The study of drug resistance and its association to Pgp began with the study of resistance to chemotherapy in the treatment of cancer and antiretroviral therapy for human immunodeficiency virus; however, the role of Pgp in the treatment of systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis has been a focus of study lately and has emerged as an important mechanism by which treatment failure occurs. The present review analyzes the role of Pgp in these autoimmune diseases.

Lack of association between serum 25-hydroxyvitamin D levels and cervical human papillomavirus infection in systemic lupus erythematosus.

Our objective was to evaluate whether vitamin D deficiency is associated with cervical human papilloma virus (HPV) infection in women with SLE. This is a cross-sectional study of 67 women with SLE. A structured questionnaire was administered to ascertain the possible risk factors associated with cervical HPV infection. A gynaecological evaluation and cervical cytology screening were made. HPV detection and genotyping was made by PCR and linear array assay. Serum 25 hydroxyvitamin D levels were quantified by chemiluminescence immunoassay. Mean age and disease duration were 44.8 ± 10.6 and 42.5 ± 11.8 years, respectively. Demographic characteristics were similar in patients with and without deficiency (<20 ng/ml and ≥20 ng/ml). There were 28.4% of women with cervical HPV infection and 68.4% had high-risk HPV infections. Patients with 25 hydroxyvitamin D levels <20 ng/ml had a higher prevalence of cervical HPV infection than those with levels ≥20 ng/ml (30.7% vs. 25.8%; p = 0.72). We found no significant difference when high-risk HPV infection was evaluated (36.8% vs. 31.5%; p = 0.73). In conclusion, women with SLE have a high prevalence of vitamin D deficiency and cervical HPV infection. However, we found no association between vitamin D deficiency and cervical HPV.