Evaluation of humoral immunity profiles to identify heart recipients at risk for development of severe infections: A multicenter prospective study.

BACKGROUND: New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections. METHODS: We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV). To evaluate potential immunologic mechanisms leading to IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical follow-up period lasted 6 months. Clinical outcome was need for intravenous anti-microbials for therapy of infection. RESULTS: During follow-up, 53 patients (31.2%) developed at least 1 severe infection. We confirmed that IgG hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for infection in general, bacterial infections in particular, and CMV disease. At Day 7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was more strongly associated with the outcome (adjusted odds ratio 7.40; 95% confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of anti-CMV antibody titers and lower anti-PPS antibody concentrations were independent predictors of CMV disease and bacterial infections, respectively. Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection. CONCLUSION: Early immunologic monitoring of humoral immunity profiles proved useful for the identification of heart recipients who are at risk of severe infection.

Nonpenetrating deep sclerectomy as an effective treatment of glaucoma related to familial amyloid polyneuropathy.

PURPOSE: To present the clinical course and treatment by nonpenetrating deep sclerectomy (NPDS) of open-angle glaucoma secondary to familial amyloid polyneuropathy (FAP). PATIENTS AND METHODS: In a series of 10 patients with FAP in a tertiary ophthalmology center, 4 eyes of 3 patients required glaucoma filtration surgery and NPDS with implant, and local intraoperative mitomycin C application was performed. Intraocular pressure and anatomic bleb functionality were measured. We performed a retrospective review of data from medical charts of the 10 FAP patients, which included demographics, incidence and treatment of glaucoma, and previous vitrectomy. RESULTS: NPDS resulted in normalization of intraocular pressure in all 4 eyes. Ten eyes (6 patients) of the studied group underwent vitrectomy because of amyloid opacities, 7 eyes (4 patients) had glaucoma, 6 of the eyes with glaucoma were previously vitrectomized, and 4 of them subsequently required glaucoma surgery. CONCLUSIONS: NPDS is an effective treatment of FAP glaucoma. Previously vitrectomized eyes have a more severe course of glaucoma and more frequently require filtration surgery.

Ocular adverse events of systemic inhibitors of the epidermal growth factor receptor: report of 5 cases.

PURPOSE: To describe the ocular effects associated with the administration of the systemic epidermal growth factor receptor (EGFR) inhibitors panitumumab and erlotinib. DESIGN: Retrospective, noncomparative interventional case series. PARTICIPANTS: Ten eyes of 5 patients in treatment with systemic EGFR inhibitors, 4 patients with erlotinib for end-stage lung carcinoma, and 1 patient with panitumumab for end-stage colorectal cancer. METHODS: Data collected from charts included gender, age at presentation, systemic disease, and clinical presentation in each eye. MAIN OUTCOME MEASURES: Demographics on presentation and clinical findings. RESULTS: Multiple epithelial defects were observed in all 10 eyes, corneal melting and thinning were observed in 3 eyes of 2 patients, 2 eyes of 1 patient presented with lower lid ectropion, and 2 eyes of 2 patients presented with corneal perforation, both requiring a penetrating keratoplasty. CONCLUSIONS: Severe ocular side effects, including corneal perforation, may be associated with the use of the EGFR inhibitors panitumumab and erlotinib.

Two cases of drug-induced orbital inflammatory disease.

Orbital inflammatory disease (OID) includes all inflammatory processes affecting the orbit. Although several aetiologies are recognised, a cause may not be elucidated. We describe 2 cases in which drugs (hyaluronidase and zoledronic acid) were the cause of OID. In patients with a clinical picture of OID simulating an orbital cellulitis, the recent drug history should be considered as a possible aetiology, and treatment with steroids with or without a biopsy should be considered after an infection has been excluded.

Effects of infliximab in the treatment of refractory posterior uveitis of Behçet's disease after withdrawal of infusions.

To determine the efficacy of infliximab treatment in refractory posterior uveitis in Behçet's disease after withdrawal of infusions. Four patients with posterior uveitis secondary to Behçet's disease were treated with infliximab until complete remission and were followed after withdrawal of infusions. Intra-ocular inflammation was assessed using the binocular indirect ophthalmoscopy score, best-corrected visual acuity (BCVA) and foveal thickness measured by optic coherence tomography (OCT). All the patients included in the study were treated with infliximab for a minimum of 12 months and were in complete remission. None of the patients were taking steroids or immunosuppressants. Main follow-up after withdrawal of infusions was 7.5 months. Two out of four patients (50%) maintained complete remission of posterior uveitis. BCVA was stable in seven eyes. OCT showed worsening in macular edema in the two eyes of the patients with reactivation. Infliximab is an efficient long-term treatment for refractory posterior uveitis. Repeated infusions are required to maintain long-term remission which may be sustained on discontinuation of the drug.

Impacto del uso de rosuvastatina en los primeros días de un síndrome coronario agudo en la fiunción endotelial y el poder oxidativo / Influence of rosuvastatin in endothelial function and oxidative stress, in patients with acute coronary syndrome

PURPOSE: The endothelial function is the cornerstone of several cardiovascular disease. In this trial we compared how the Nitric Oxide (NO) and Oxidative Stress (OS) serum levels, as surrogate markers of endothelial function, change in patients who received (or not) rosuvastatin during the first seven days of an acute coronary syndrome (ACS). METHODS: Twenty-two patients with ACS (age:66 +/- 9 years, gender: ten female and 12 male) were randomized in two groups. Patients in the first group (G1) received the conventional treatment for an ACS, plus placebo. The other group (G2) additionally received a daily oral dose of 40 mg of rosuvastatin. We measured the blood levels of nitrates and OS in both groups twice: at baseline (admission to Intensive care unit) and seven days after. The statistical analysis was performed using the paired t-test or the Chi2 test depending of the variables. Statistical significance was considered with a p < 0.05. RESULTS: Groups (G1 and G2) differed statistically on age (G1=71 years +/- 10 vs. G2 63 +/- 9 years, p=0.04). After 7 days of the ACS onset, ON levels diminished on 21% (p=0.17) in G1, but raised on 24% in the group who re- ceived rosuvastatin (p=0.005), with statistically difference between groups (p=0.005). On the other hand, the OS, augmented statistically on both groups: G1 (17%, p<0.001) and G2 (13%, p<0.001), without any difference between groups (p=0.77). Conclusion: The endothelial dysfunction in the first days of an ACS is accentuated, but with the use of rosuvastatina, the endothelial function improves. In contrast, the OS increase in both groups, without differences between groups.

[Influence of rosuvastatin in endothelial function and oxidative stress, in patients with acute coronary syndrome]. / Impacto del uso de rosuvastatina en los primeros días de un síndrome coronario agudo en la fiunción endotelial y el poder oxidativo.

PURPOSE: The endothelial function is the cornerstone of several cardiovascular disease. In this trial we compared how the Nitric Oxide (NO) and Oxidative Stress (OS) serum levels, as surrogate markers of endothelial function, change in patients who received (or not) rosuvastatin during the first seven days of an acute coronary syndrome (ACS). METHODS: Twenty-two patients with ACS (age:66 +/- 9 years, gender: ten female and 12 male) were randomized in two groups. Patients in the first group (G1) received the conventional treatment for an ACS, plus placebo. The other group (G2) additionally received a daily oral dose of 40 mg of rosuvastatin. We measured the blood levels of nitrates and OS in both groups twice: at baseline (admission to Intensive care unit) and seven days after. The statistical analysis was performed using the paired t-test or the Chi2 test depending of the variables. Statistical significance was considered with a p < 0.05. RESULTS: Groups (G1 and G2) differed statistically on age (G1=71 years +/- 10 vs. G2 63 +/- 9 years, p=0.04). After 7 days of the ACS onset, ON levels diminished on 21% (p=0.17) in G1, but raised on 24% in the group who re- ceived rosuvastatin (p=0.005), with statistically difference between groups (p=0.005). On the other hand, the OS, augmented statistically on both groups: G1 (17%, p<0.001) and G2 (13%, p<0.001), without any difference between groups (p=0.77). CONCLUSION: The endothelial dysfunction in the first days of an ACS is accentuated, but with the use of rosuvastatina, the endothelial function improves. In contrast, the OS increase in both groups, without differences between groups.

Evaluación de cuatro protocolos de sincronización para inseminación a tiempo fijo en vacas Bos indicus lactantes / Evaluation of four synchronization protocols for fixed-time artificial insemination in Bos indicus lactating cows

El objetivo del estudio fue evaluar cuatro protocolos de sincronización para inseminación artificial a tiempo fijo (IATF) en vacas Bos indicus lactantes. Se seleccionaron 120 vacas Brahman entre 45 y 120 días postparto y fueron ubicadas aleatoriamente en uno de cuatro tratamientos. El tratamiento Crestar consistió en un implante auricular de norgestomet y una inyección de norgestomet y valerato de estradiol, el día 9 se retiró el implante y se aplicó eCG; la IATF se realizó 48-52 horas después. El tratamiento GPG consistió en una inyección de gonadorelina, el día 7 una inyección de D-cloprostenol y el día 9 una segunda inyección de gonadorelina e IATF 18-22 horas después. El tratamiento GPE fue similar al tratamiento GPG, excepto que la segunda dosis de GnRH fue reemplazada por benzoato de estradiol (BE) el día 8 e IATF 30-32 horas después. El tratamiento CIDR-B consistió en la aplicación del dispositivo intravaginal más una inyección de BE y otra de progesterona, 7 días después se retiró el dispositivo y se aplicó D-cloprostenol, el día 8 una inyección de BE y la IATF 30-32 horas después. El diagnostico de preñez fue determinado mediante ultrasonografia transrectal 35 días después de la IATF. El tratamiento Crestar tuvo una tasa de preñez superior (P<0,01) a los demás tratamientos (55,7 por ciento versus 19,4 por ciento, 22,5 por ciento y 21,8 por ciento, respectivamente). Los resultados del presente estudio indican que es posible obtener tasas de preñez aceptables con la IATF en vacas B. indicus lactantes y que los tratamientos con dispositivos de liberación de progesterona más eCG pueden mejorar el desempeño reproductivo de las vacas.

The objective of this study was the evaluation of four synchronization protocols for fixed-time artificial insemination (FTAI) in Bos indicus lactancting cows. Brahman cows (n=120) between 60 and 120 days postpartum were randomly assigned to one of four syncronization treatments. The Crestar treatment consisted of the aplication of ear implant of norgestomet and an injection of norgestomet and estradiol valerate, on day 9 the implant was removed and the cows received an eCG injection; the FTAI was performed 48-52 hours later. In the GPG treatment the cows received an injection of gonadorelina on day 0, an injection of D-cloprostenol on day 7, a second injection of gonadorelina on day 8 and FTAI 18-22 hours later. The GPE treatment was similar to GPG, but the second dose of gonadorelina was replaced by an estradiol benzoate (EB) injection and the FTAI was performed 30-32 hours later. The CIDR-B treatment consisted of the aplication of intravaginal device, an injection of EB and progesterone, the device was removed 7 days later, at the same time the cows received an injection of D-cloprostenol, on day 8 the cows received an injection of EB and FTAI 30-32 hours later. Pregnancy was diagnosed by transrectal ultrasonography 35 days after TAI. Crestar treatment has a higher pregnancy rate (P<0,01) than the other treatments (55.7 vs 19.4, 22.5 y 21.8% respectively). The findings of this experiment show that is possible to get acceptable pregnancy rates with FTAI in B. indicus lactating cows and progesterone releasing devices plus eCG treatments should improve reproductive performance of cows.

Intravitreal bevacizumab as initial treatment for choroidal neovascularization associated with presumed ocular histoplasmosis syndrome.

PURPOSE: To report a case of juxtafoveal choroidal neovascularization in a patient with presumed ocular histoplasmosis syndrome (POHS) who was treated with intravitreal injection of bevacizumab (Avastin) as initial treatment. METHODS: A 23-year-old woman with POHS presented with sudden dimness of vision and metamorphopsia in the right eye. The patient was examined with ophthalmoscopy, fluorescein angiography, and optical coherence tomography (OCT). RESULTS: Fundus examination, fluorescein angiography, and OCT of the right eye revealed a juxtafoveal choroidal neovascularization. Intravitreal injection of bevacizumab was performed with a postoperative improvement of visual acuity and resolution of the distortion. CONCLUSIONS: This case report describes a case of juxtafoveal choroidal neovascularization associated with POHS that responded remarkably well to intravitreal injection of bevacizumab.

[Mixed cryoglobulinemia and related immunological disorders after hepatic transplantation for hepatitis C cirrhosis. Case report]. / Crioglobulinemia mixta y otras alteraciones inmunologicas en trasplante hepatico por cirrosis por virus de la hepatitis C. Reporte de un caso.

Cryoglobulinemia may be found in up to 30% of patients that had received liver transplants after hepatitis C virus (HCV) cirrhosis. Three types of cryoglobulinemia are recognized: type I, composed of monoclonal immunoglobulins associated with lymphoproliferative diseases and myeloma; type II cryoglobulinemia are comprised of a monoclonal component which has rheumatoid factor activity and hence binds to polyclonal immunoglobulins (in certain parts of the world have been found to be associated with hepatitis C infection); and type III cryoglobulinemia consist exclusively of polyclonal immunoglobulins with rheumatoid factor activity (associated with connective tissue diseases and chronic infections including hepatitis C). Immunocompetence, autoimmunity and clonal expansion of B cell lymphocytes have not been analysed simultaneously in previous reports of patients with cryoglobulinemia after liver transplantation. We here describe immunological abnormalities associated with cryoglobulinemia in a patient who had received liver transplant for HCV cirrhosis. In addition, in the present work HCV RNA determination was performed directly in the cryocrit and not only in peripheral blood. We have observed enrichment of HCV RNA in the cryoprecipitates which might be a better demonstration of the possible role of HCV in the pathogenesis of the cryoglobulinemia.

[Antiphospholipid antibodies evolving into connective tissue disease: follow-up study of women with recurrent misscarriage]. / Anticuerpos antifosfolipídicos y evolución a conectivopatía: estudio de seguimiento de mujeres con abortos recurrentes.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the clinical and immunologic profile, the rate of progression to connective tissue disease and the possible predictors of evolution in patients with antiphospholipid antibodies and abortions. PATIENTS AND METHOD: In a prospective follow-up study, we determined the prevalence of antiphospholipid antibodies as well as other autoimmune abnormalities and the evolution to connective tissue disease in 200 women with unexplained recurrent abortions. IgG and IgM anticardiolipin antibodies were determined by ELISA and the lupus anticoagulant was determined by means of coagulometric tests. RESULTS: Of 200 women with pregnancy losses, 69 (34.5%) had antiphospholipid antibodies. Thirty-one of 200 women (15.5%) had high or moderate positive anticardiolipin antibodies. During a mean follow-up of 32 months, 9 (13%) antiphospholipid-antibody-positive patients developed features of lupus- like disease or systemic lupus erythematosus. A low total hemolytic complement, increased circulating immune complexes and positive antinuclear antibodies (ANA) were more common in those patients evolving to a connective tissue disorder (p < 0.001, p = 0.003 and p < 0.001, respectively). Positive ANA in women with antiphospholipid antibodies predicted independently the evolution to a connective tissue disorder [Cox proportional hazard model; relative hazard = 4.92, p = 0.04]. CONCLUSIONS: A subgroup of patients with antiphospholipid antibodies and abortions may progress to a connective tissue disorder. A positive antinuclear antibody test result could be useful to identify those patients with antiphospholipid antibodies and abortions who are prone to evolve into a systemic autoimmune disease.

Anticuerpos antifosfolipídicos y evolución a conectivopatía: estudio de seguimiento de mujeres con abortos recurrentes / Antiphospholipid antibodies evolving into connective tissue disease: follow-up study of women with recurrent misscarriage

FUNDAMENTO Y OBJETIVO: El objetivo de este estudio fue la determinación del perfil clínico e inmunológico, la tasa de progresión a conectivopatía y posibles variables predictoras de evolución en pacientes con abortos y anticuerpos antifosfolipídicos. PACIENTES Y MÉTODO: Estudiamos prospectivamente la prevalencia de anticuerpos antifosfolipídicos, otras alteraciones autoinmunitarias y su evolución a conectivopatía en 200 mujeres con aborto recurrente. Los anticuerpos antifosfolipídicos se determinaron mediante técnica de enzimoinmunoanálisis (anticuerpos anticardiolipina IgG e IgM) y por técnicas coagulométricas (anticoagulante lúpico). RESULTADOS: De 200 mujeres con abortos, 69 (34,5 per cent) tuvieron anticuerpos antifosfolipídicos. Treinta y un pacientes (15,5 per cent) tenían anticuerpos anticardiolipina a título moderado-alto. Tras una media de seguimiento de 32 meses, 9 pacientes con anticuerpos antifosfolipídicos (13 per cent) evolucionaron a lupus eritematoso sistémico o a enfermedad lupus like. Se observaron con más frecuencia cifras bajas de complemento hemolítico total, concentraciones elevadas de inmunocomplejos circulantes y anticuerpos antinucleares positivos en las pacientes con anticuerpos antifosfolipídicos que evolucionaron a conectivopatía frente a las que no lo hicieron (p < 0,001, p = 0,003 y p < 0,001, respectivamente). La positividad de anticuerpos antinucleares en las pacientes con anticuerpos antifosfolipídicos predijo de forma independiente la evolución a conectivopatía mediante análisis de regresión de Cox (riesgo relativo = 4,92; p = 0,04).CONCLUSIONES: Un subgrupo de pacientes con abortos y anticuerpos antifosfolipídicos puede evolucionar a conectivopatía. La positividad de los anticuerpos antinucleares podría utilizarse para identificar a pacientes con abortos y anticuerpos antifosfolipídicos positivos que a lo largo de su evolución pueden presentar síntomas indicativos de evolución a conectivopatía sistémica (AU)