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Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumoral overproduction of FGF-23. Due to local recurrence, we describe the long-term efficacy and safety profile of burosumab, an anti-FGF-23 monoclonal antibody, in a TIO patient after three unsuccessfully surgical attempts. INTRODUCTION: TIO is a rare paraneoplastic syndrome caused by tumoral overproduction of fibroblast growth factor 23 (FGF23), resulting in hyperphospaturia, hypophosphatemia, and osteomalacia. Surgery is the only definitive treatment, but tumor can locally recur, even after years from primary surgery. Furthermore, some tumors cannot be removed by surgery due to their location. METHODS: We describe the case of a 54-year-old woman affected by recurrent TIO who, after three unsuccessful surgical attempts of tumor removal, was treated with burosumab, an anti-FGF-23 monoclonal antibody. RESULTS: The patient was referred to our Bone Unit after experiencing several fractures in different sites, both traumatic and non-traumatic. At the time of first evaluation, at the age of 46, serum-phosphate (SP) was 1.2 mg/dL (reference range (RR) 2.5-4.5), 24-h urinary phosphate was 842 mg (RR 400-1000), and intact-FGF-23 was 117 pg/mL (RR 25-45). Imaging showed a metabolic pre-sacral lesion that firstly underwent to exploratory laparotomy. Then, patient underwent to surgical excision of tumor. After 18 months of well-being, tumor relapsed and even the subsequent surgery was not able to completely remove it. Since 2015, patient was maintained in phosphorus supplements and 1,25(OH)2vitamin D3, but SP levels never normalized. In September 2019, she was started on burosumab, initially at the dose of 0.3 mg/kg/month, progressively increased to the current 0.8 mg/kg/month, with great improvement of pain, physical performance, and normalization of SP levels. Burosumab was temporary and cautionary discontinued for COVID-19 pneumonia, with a worsening of SP. After restart of burosumab, biochemistry returned to normal. CONCLUSIONS: To our knowledge, this is the first European patient affected by TIO treated with burosumab for more than 2 years. Burosumab is a promising therapy in the medical treatment of TIO refractory or not eligible for definitive surgery, with good efficacy and safety profile.
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COVID-19 , Hipofosfatemia , Osteomalacia , Síndromes Paraneoplásicos , Femenino , Humanos , Persona de Mediana Edad , Osteomalacia/tratamiento farmacológico , Osteomalacia/etiología , COVID-19/complicaciones , Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndromes Paraneoplásicos/tratamiento farmacológico , Síndromes Paraneoplásicos/etiología , Hipofosfatemia/tratamiento farmacológico , Hipofosfatemia/etiología , Hipofosfatemia/patología , Factores de Crecimiento de Fibroblastos , FosfatosRESUMEN
Ultrafast semiconductor disk lasers (SDLs) passively modelocked using semiconductor saturable absorbers mirrors (SESAMs) generate optical frequency combs (OFCs) with gigahertz line spacings - a regime where solid-state and fiber lasers struggle with geometrical and Q-switching limitations. We stabilized both the frequency comb spacing and the offset without any additional external optical amplification or pulse compression. The overall noise performance is competitive with other gigahertz OFCs. A SESAM-modelocked vertical external-cavity surface-emitting laser (VECSEL) at a center wavelength around 1 µm generates 122-fs pulses with 160 mW average output power and we only needed 17-pJ pulse energy coupled into a silicon nitride (Si3N4) waveguide for supercontinuum generation (SCG) and OFC offset stabilization.
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With a modelocked integrated external-cavity surface emitting laser (MIXSEL) we achieved a pulse duration of 144 fs. The MIXSEL belongs to the family of optically pumped semiconductor disk lasers. The MIXSEL operates at a center wavelength of 1033 nm with a 13-nm full width at half maximum optical bandwidth, at a pulse repetition rate of 2.73 GHz, and at an average output power of 30 mW. This new record result was obtained with an optimized multipair dielectric top-coating, a large bandgap AlAsxP1-x material for strain compensation, a nonperiodic InGaAs quantum well gain structure, and an improved thermal management.
RESUMEN
Compact optically pumped passively modelocked semiconductor disk lasers (SDLs) based on active quantum wells (QWs) such as vertical external-cavity surface-emitting lasers (VECSELs) or modelocked integrated external-cavity surface-emitting lasers (MIXSELs) are wavelength-versatile sources that offer a unique combination of gigahertz pulse repetition rates and short pulse durations. In this paper, we present record-short pulses of 184 fs from a gigahertz MIXSEL emitting at a center wavelength of 1048 nm. This result comes at the expense of low optical-to-optical pump efficiency (<1%) and average output power limited to 115 mW. We experimentally observe that shorter pulses significantly reduce the macroscopic gain saturation fluence and develop a QW model based on rate equations to reproduce the gain saturation behavior and quantitatively explain the VECSEL and MIXSEL modelocking performances. We identify spectral hole burning as the main cause of the reduced gain at shorter pulse durations, which in combination with the short lifetime of the excited carriers strongly reduces the optical pump efficiency. Our better understanding will help to address these limitations in future ultrafast SDL designs.
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We present a high-peak-power SESAM-modelocked thin-disk laser (TDL) based on the gain material Yb-doped lutetia (Yb:Lu2O3), which exceeds a peak-power of 10 MW for the first time. We generate pulses as short as 534 fs with an average power of 90 W and a peak power of 10.1 MW, and in addition a peak power as high as 12.3 MW with 616-fs pulses and 82-W average power. The center lasing wavelength is 1033 nm and the pulse repetition rates are around 10 MHz. We discuss and explain the current limitations with numerical models, which show that the current peak power is limited in soliton modelocking by the interplay of the gain bandwidth and the induced absorption in the SESAM with subsequent thermal lensing effects. We use our numerical model which is validated by the current experimental results to discuss a possible road map to scale the peak power into the 100-MW regime and at the same time reduce the pulse duration further to sub-200 fs. We consider Yb:Lu2O3 as currently the most promising gain material for the combination of high peak power and short pulse duration in the thin-disk-laser geometry.
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We present semiconductor saturable absorber mirrors (SESAMs) that can potentially support femtosecond pulses from ultrafast thin disk lasers (TDLs) with high average power approaching the kW-power level and high pulse energy in the range of 100 µJ to 1 mJ at megahertz pulse repetition rates. For high-power operation, the SESAM parameters will ultimately limit the shortest pulse duration from a soliton mode-locked laser before mode locking instabilities such as multiple pulsing instabilities and continuous wave (cw) breakthrough start to occur. Currently shorter pulses are prevented due to the inverse saturable absorption that becomes stronger with shorter pulses and results in a shift of the "rollover" of the nonlinear SESAM reflectivity towards lower fluences. Here we discuss a novel SESAM design that addresses these issues and can be grown by metal-organic vapor phase epitaxy (MOVPE), an attractive epitaxial growth technology for manufacturing.
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We present a thorough investigation of surface deformation and thermal properties of high-damage threshold large-area semiconductor saturable absorber mirrors (SESAMs) designed for kilowatt average power laser oscillators. We compare temperature rise, thermal lensing, and surface deformation of standard SESAM samples and substrate-removed SESAMs contacted using different techniques. We demonstrate that for all cases the thermal effects scale linearly with the absorbed power, but the contacting technique critically affects the strength of the temperature rise and the thermal lens of the SESAMs (i.e. the slope of the linear change). Our best SESAMs are fabricated using a novel substrate-transfer direct bonding technique and show excellent surface flatness (with non-measureable radii of curvature (ROC), compared to astigmatic ROCs of up to 10 m for standard SESAMs), order-of-magnitude improved heat removal, and negligible deformation with absorbed power. This is achieved without altering the saturation behavior or the recovery parameters of the samples. These SESAMs will be a key enabling component for the next generation of kilowatt-level ultrafast oscillators.
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This study examined the prevalence of three human herpesviruses (HHV), namely HHV-4 (Epstein-Barr virus/EBV), HHV-6b and HHV-7 in leucoreduced blood products obtained from the Sainte-Justine Hospital blood bank. A total of 100 specimens, including 34 red blood cell concentrates, 33 platelet bags and 33 plasma units, were collected and screened by a sensitive PCR assay using virus-specific primers. Positive units were then retested by quantitative PCR. Of the 100 specimens, one platelet unit tested positive for EBV.
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Bancos de Sangre/estadística & datos numéricos , Herpesvirus Humano 4/aislamiento & purificación , Plasma/virología , Bancos de Sangre/normas , Células Sanguíneas/virología , HumanosRESUMEN
PURPOSE: The authors evaluated the relative risk of developing radiation-induced breast cancer (BC) in women treated with radiotherapy for Hodgkin's disease (HD) and analysed the imaging features of these breast neoplasms. MATERIALS AND METHODS: We retrospectively studied 54 women who had all undergone radiotherapy between 1980 and 2010 (median age, 36.6 years). Women aged ≤30 years were screened with clinical breast examination, ultrasound (US) and, if necessary, mammography; women >30 years had clinical breast examination, US and mammography. Three women underwent magnetic resonance (MR) imaging as well. RESULTS: Mammography detected seven invasive breast cancers in 6/54 women (11.1%). Median age at diagnosis was 26.1 years for HD and 42.4 for breast cancer. Breast cancer was diagnosed following a median latent period from radiotherapy of 15.1 years. Mean radiation dose was 37.6 Gy in women who developed breast cancer and 31.3 Gy in the other women. CONCLUSIONS: In our study, women who were exposed to radiation for HD had a 6.2-fold higher risk of developing breast cancer than the general population. In consideration of the young age and high breast density, women aged ≤30 years should be monitored by US and MR imaging; women aged >30 years should be monitored by US, mammography and, when necessary, MR imaging.
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Neoplasias de la Mama/patología , Enfermedad de Hodgkin/radioterapia , Neoplasias Inducidas por Radiación/patología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/terapia , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/terapia , Dosis de Radiación , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
Hepatic fibrosis is an integral element in the progression of chronic liver disease. Elevated hepatic interleukin (IL)-8 is an important contributor to fibrosis in patients chronically infected with the hepatitis C virus (HCV). Thalidomide has been used to reduce liver inflammation and fibrosis in HCV-infected patients, but its impact on HCV replication remains unclear. This study examined the effect of thalidomide on HCV replication in vitro. Results revealed that while thalidomide reduced IL-8 and nuclear factor kappa B (NF-κB) activity by 95% and 46% in Huh-7 cells, increasing concentrations of thalidomide correlated with a linear rise in HCV replication (17-fold at 200 µm). The NF-κB inhibitors, wedelolactone and NF-κB activation inhibitor-1, which mimic the actions of thalidomide by preventing phosphorylation and activation of IκB kinase (IKK) and hence block NF-κB activity, increased HCV RNA by 18- and 19-fold, respectively. During in vitro HCV replication in Huh-7 cells, we observed a 30% increase in IKKα protein and 55% decrease in NF-κB(p65)/RelA protein relative to cellular ß-actin. Ectopic expression of IKKα to enhance the inactive form of IKK in cells undergoing virus replication led to a 13-fold increase in HCV RNA. Conversely, enhanced expression of NF-κB(p65)/RelA in infected cells resulted in a 17-fold reduction in HCV RNA. In conclusion, HCV RNA replication was significantly augmented by the inhibition of IKK activation and subsequent NF-κB signalling, whereas a restoration of NF-κB activity by the addition of NF-κB/RelA markedly reduced HCV replication. This study lends added importance to the role of the NF-κB signalling pathway in controlling HCV replication.
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Inhibidores Enzimáticos/farmacología , Hepacivirus/crecimiento & desarrollo , Quinasa I-kappa B/antagonistas & inhibidores , Talidomida/farmacología , Replicación Viral/efectos de los fármacos , Línea Celular , Hepatocitos/efectos de los fármacos , Hepatocitos/inmunología , Hepatocitos/virología , Humanos , Interleucina-8/inmunología , FN-kappa B/inmunología , ARN Viral/biosíntesis , ARN Viral/genéticaRESUMEN
In 178-kidney transplanted patients (KTxp), the prevalence of hypovitaminosis-D, the presence and novel development of left ventricular hypertrophy(LVH) and the correlations between native Vitamin-D (25OHD) and LVH were evaluated during the 1st year of transplantation (KTx). Clinical and instrumental data were recorded at pre-KTx and at one (T1) and 12 (T12) months after KTx. 25OHD levels were considered sufficient (s25OHD, ≥ 30 ng/dL) or insufficient (i25OHD, < 30 ng/dL). 25OHD correlated at T1 with parathormone(PTH), and at T12 with 25OHD-T1 and PTH-(T1,T12). At T12, s25OHD (15%) had higher 25OH and alkaline phosphatase (ALP), lower Ca, at T1, and lower PTH-(T1, T12) than i25OH-T12. At T1, KTxp with LVH (LVH-T1pos, 42%) were older and with longer dialysis vintage than LVH-T1neg. At T12, KTxp with LVH (LVH-T12pos, 53%) were older, with higher systolic blood pressure (SBP) at T12 than LVH-T12neg. No relation between 25OHD and LVH were found. Novel LVH was found in 14% of KTxp. They were older, had higher SBP-T12 and lower serum albumin-T12 than the others. LVH-modifications and 25OHD were not correlated. Hypovitaminosis-D is highly prevalent in KTxp. LVH correlates with different risk factors according to the time elapsed from KTx. However, during the 1st year of KTx, no relationship between LVH and 25OHD was observed.
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Hipertrofia Ventricular Izquierda/epidemiología , Trasplante de Riñón , Receptores de Trasplantes , Deficiencia de Vitamina D/epidemiología , Vitamina D/sangre , Adulto , Factores de Edad , Fosfatasa Alcalina/sangre , Calcio/sangre , Femenino , Humanos , Hipertrofia Ventricular Izquierda/sangre , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Prevalencia , Estudios Retrospectivos , Albúmina Sérica , Deficiencia de Vitamina D/sangreRESUMEN
Coronary artery calcifications(CACs), are related to the increased cardiovascular mortality during kidney transplantation(KTx). Using coronary-CT performed at 1 month(T0) and 5 years(T5) after KTx we evaluated: (1) the prevalence of CACs; (2) the clinical and biochemical factors related to CACs; 3) the factors implicated with CACs progression. We evaluated 67-pts selected from the 103-pts transplanted in our unit between 2007 and 2008. Clinical and biochemical parameters were recorded at the time of pre-KTx evaluation and for five years after KTx. Coronary-CT for the Agatson score (AS) evaluation was performed at T0 and at T5, and CACs progression was determined. At baseline AS was 45 [0-233]. At T5 AS was 119 [1-413]. At T0, 69% of patients had CACs. Age and dialytic vintage were the main independent variables related to CACs. At T5, CACs were present in 76% of patients. Age was the only independent factor in determining CACs. A progression of CACs was observed in 74% of patients. They were older, had higher CACs-T0 and higher SBP throughout the 5-years. The presence of CACs at T0 and age were the only independent factors in determining the CACs-progression. CACs-T0 had the best discriminative power for CACs progression. CACs prevalence is quite high in KTx patients; Age is strictly related to CACs; Age and the presence of CACs at baseline were the two major factors associated with the progression of CACs during the five years of follow up. CACs-T0 had the best discriminative power for progression of CACs.
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Enfermedad de la Arteria Coronaria/epidemiología , Trasplante de Riñón/estadística & datos numéricos , Calcificación Vascular/epidemiología , Adulto , Estudios de Cohortes , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/patología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Calcificación Vascular/mortalidad , Calcificación Vascular/patologíaRESUMEN
Renal biopsy (RBx) informs about kidney transplantation (KTx) prognosis. In our observational study the prevalence of histological anomalies and the prognostic role of CD45, vimentin (VIM) and periostin (POSTN) in KTx-RBx have been evaluated. One hundred forty-six KTx-RBx (2009-2012) were analysed for general histology and in immunohistochemistry for CD45, VIM and POSTN. Clinical data of the 146-KTx patients were collected at the RBx time (T0), 6 and 12 months before and after RBx. Follow-up time was 21 ± 14 months. Glomerulosclerosis was 20% glomeruli/biopsy. Tubular atrophy (TA), Interstitial infiltrate (I-Inf) and interstitial fibrosis (IF) were slight in 21-18% and 25%, moderate in 22-30% and 26% and severe in 30-18% and 28% of patients. Fifty-eight percent of patients had lesions compatible with IF-TA. CD45, VIM and POSTN correlated to each-other and to TA, I-Inf and IF. VIM and POSTN correlated to GS. CD45 and VIM correlated directly to renal function (RF) and 25(OH)VitD, while POSTN inversely to 25(OH)VitD. Thirty patients restarted dialysis (HD+). HD+ had lower T0-eGFR, and higher CD45, VIM and POSTN than HD-. POSTN resulted the strongest in discriminate for HD+ . CD45, VIM and POSTN correlate to each-other and predict graft outcome. POSTN was the strongest in discriminate for HD+. 25(OH)VitD might influence inflammation and fibrosis in KTx.
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Moléculas de Adhesión Celular/metabolismo , Enfermedades Renales/etiología , Trasplante de Riñón/efectos adversos , Riñón/metabolismo , Antígenos Comunes de Leucocito/metabolismo , Vimentina/metabolismo , Adulto , Biomarcadores/metabolismo , Biopsia , Transición Epitelial-Mesenquimal , Femenino , Fibrosis , Supervivencia de Injerto , Humanos , Inmunohistoquímica , Riñón/patología , Riñón/fisiopatología , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: Sickle cell anemia (SCA) and ß -thalassemia major are well-recognized beta-globin gene disorders of red blood cells associated to mortality and morbidity included bone morbidities due to ineffective erythropoiesis and bone marrow expansion, which affect every part of the skeleton. While there are an abundance of described disease manifestations of the head and neck, the manner of paranasal sinuses involvement and its relations to ß-thalassemia and SCA process was not studied yet. Therefore, the aim of this study was to investigate a possible increased risk of rhinosinusitis and the real pathogenetic mechanism of it, comparing these two hematological diseases using msCT, gold standard for paranasal sinuses evaluation. METHODS: A retrospective analysis of 90 patients affected by ß-thalassemia major or SCA (respectively 59 and 31) underwent allogeneic bone marrow transplantation (BMT), and 44 control subjects was performed. Both patient categories and control group have been subjected to hematological and radiological evaluation using 64-multidetector-row CT scanner without contrast injection. RESULTS: Statistical analysis reveals that patients of the two study groups exhibit a significantly increased risk of sinusitis in comparison with the normal controls (RR: 3.55 for ß-thalassemic pediatric subjects; RR: 3.35 for SCA pediatric subjects). A significant difference (pâ¯<â¯0,5) was found between the ß -thalassemic patients on the one side, and SCA and control group on the other side, with regard to the evaluation of the typical anatomic alteration of maxillary sinus: ß-thalassemic children had significant increase in the bone thickness of anterior and lateral sinus walls and significant reduction in volume and density compared to SCA patients and control group, with normal conditions of these parameters. CONCLUSIONS: In these hematological patients, there is an increased incidence of sinonasal infections due their therapy-induced immunosuppression post transplantation. In ß-thalassemic patients, furthermore, the specific anatomical variants play an important confounding factor in radiological interpretation of CT images. Therefore, a cranio-facial CT scan evaluation could be a useful tool in the management of upper airway infections after BMT and should be a routinely exams in order to avoid useless surgical or antibiotic approaches.
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Anemia de Células Falciformes/complicaciones , Trasplante de Médula Ósea/efectos adversos , Rinitis/fisiopatología , Sinusitis/fisiopatología , Talasemia beta/complicaciones , Adolescente , Anemia de Células Falciformes/cirugía , Niño , Preescolar , Enfermedad Crónica , Femenino , Humanos , Masculino , Estudios Retrospectivos , Rinitis/complicaciones , Rinitis/epidemiología , Medición de Riesgo , Sinusitis/complicaciones , Sinusitis/epidemiología , Tomografía Computarizada por Rayos X , Adulto Joven , Talasemia beta/cirugíaRESUMEN
INTRODUCTION: AHSG, a serum glycoprotein with recognized anti-calcification activity, has also been suggested to modulate both bone formation and resorption. Though the bulk of AHSG is mostly synthesized in the liver, it has been claimed that also bone cells might produce it. However, the extent of the bone AHSG production and the potential controlling factors remain to be definitively proven. A relevant number of studies support the notion that FGF23, a bone-derived hormone, not only regulates the most important mineral metabolism (MM) related factors (phosphate, parathyroid hormone, vitamin D, etc.), but might be also involved in cardiovascular (CV) outcome, both in chronic kidney disease (CKD) patients and in the general population. Furthermore, in addition to some direct autocrine and paracrine effects in bone, FGF23 has been suggested to interact with AHSG. In this study we investigated if AHSG is really produced by bone cells, and if its bone production is related and/or controlled by FGF23, using cultured bone cells, according to a new method recently published by our group. RESULTS: Our data show that AHSG is consistently produced in osteocytes and to a far lesser extent in osteoblasts. Both FGF23 addition to the culture medium and its over-expression in osteocytes were associated with a consistent increase of both AHSG mRNA and protein, while FGF23 silencing was followed by opposite effects. Though most of these results were largely affected by the blockage of FGF23 receptors, the role of these receptors in the different experimental sets is still not completely clarified. In addition, we found that FGF23 and AHSG proteins co-localized both in cytoplasm and nucleus, which suggests a possible reciprocal interactivity. CONCLUSIONS: Our data not only confirm that AHSG is produced in bone, mainly in osteocytes, but show for the first time that its production is modulated by FGF23. Since both proteins play important roles in the bone and cardiovascular pathology, these results add new pieces to the puzzling relationship between bone and vascular pathology, in particular in CKD patients, prompting future investigations in this field.
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Factores de Crecimiento de Fibroblastos/metabolismo , Osteocitos/metabolismo , alfa-2-Glicoproteína-HS/biosíntesis , Animales , Bovinos , Células Cultivadas , Medios de Cultivo , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/genética , Técnica del Anticuerpo Fluorescente , Regulación de la Expresión Génica/efectos de los fármacos , Silenciador del Gen/efectos de los fármacos , Humanos , Masculino , Ratones Endogámicos BALB C , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteocitos/efectos de los fármacos , Regiones Promotoras Genéticas/genética , Unión Proteica/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Factores de Crecimiento de Fibroblastos/antagonistas & inhibidores , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Proteínas Recombinantes/farmacología , Tibia/efectos de los fármacos , Tibia/metabolismo , Factores de Tiempo , alfa-2-Glicoproteína-HS/genéticaRESUMEN
Post-transplant patients undergoing prolonged Cyclosporine A (CsA) immunosuppressive therapy were reported to have an increased incidence of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders. EBV-infected B cells cultured with CsA demonstrated increased EBV B-cell out-growth as compared to those cultured without CsA. Peripheral blood mononuclear cells (PBMC), following infection with EBV and CsA treatment, demonstrated increased IL-6 activity in the culture supernatant. The induction of IL-6 appeared to differ within the various lymphocyte populations. In monocytes and B cells, IL-6 expression was preferentially induced by EBV, and initiated by the binding of the two major virion glycoproteins, gp350 and gp220, to CD21, or a CD21-like receptor. Expression of IL-6 in T cells appeared to be due mainly to CsA. B cells also expressed IL-6 following EBV exposure, but not following CsA treatment. EBY-immortalized B-cell lines cultured with CsA exhibited both an increased number of cells expressing viral lytic-cycle antigens and increased amounts of lytic-cycle proteins. IL-6, which was induced by CsA in PBMC, was also capable of inducing the lytic viral cycle in several EBV-immortalized cells. When IL-6 was expressed, it was shown to act as an autocrine growth factor for B cells and to inhibit the immune system allowing for the promotion of B-cell tumors by impairing lymphokine-activated killer cells. Thus CsA treatment, in promoting both increased numbers of lytic EBV B cells and expression of the EBV paracrine growth factor, IL-6, within the microenvironment of EBV B:T cell and EBV B:monocyte interactions, may lead to increased EBV B-cell immortalization and ultimately result in the promotion of B-cell lymphomas in immunosuppressed patients.
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Linfocitos B/patología , Cocarcinogénesis , Ciclosporina/efectos adversos , Herpesvirus Humano 4/patogenicidad , Inmunosupresores/efectos adversos , Interleucina-6/biosíntesis , Trastornos Linfoproliferativos/etiología , Proteínas de Neoplasias/biosíntesis , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Linfocitos B/virología , Transformación Celular Neoplásica , Transformación Celular Viral , Células Cultivadas , Ciclosporina/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Genes Virales , Infecciones por Herpesviridae , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Huésped Inmunocomprometido , Inmunosupresores/farmacología , Interleucina-6/genética , Interleucina-6/farmacología , Subgrupos Linfocitarios/efectos de los fármacos , Subgrupos Linfocitarios/patología , Subgrupos Linfocitarios/virología , Linfoma/etiología , Linfoma/virología , Trastornos Linfoproliferativos/genética , Trastornos Linfoproliferativos/metabolismo , Trastornos Linfoproliferativos/virología , Ratones , Ratones Desnudos , Monocitos/inmunología , Monocitos/virología , Proteínas de Neoplasias/genética , Complicaciones Posoperatorias/inmunología , Complicaciones Posoperatorias/virología , Trasplante , Infecciones Tumorales por Virus , Proteínas Virales/fisiología , Activación Viral/efectos de los fármacosRESUMEN
PURPOSE: Although binocular vision deficits occur in children who have a constant esotropia onset following significant maturation of stereopsis, it is uncertain whether adults are susceptible to changes to binocular vision. We examined binocular vision in adults with longstanding surgical monovision (> or =6 month's duration) to determine whether the binocular visual system remains susceptible to change. METHODS: Participants included 32 adults with longstanding monovision through laser-assisted in situ keratectomy or photorefractive keratectomy and 20 age-matched control subjects. After full binocular correction, binocular function was measured by using the Randot Stereoacuity Test, the Randot Preschool Stereoacuity Test, and the Worth 4-dot test at near and distance. Monovision patients were grouped as having low anisometropia (<1.5 spherical D) or moderate anisometropia (> or =1.5 spherical D). RESULTS: Non-parametric analysis of variance revealed a significant difference between group median stereoacuity (H = 16.062; P <.001). Pairwise multiple comparisons indicated both groups with monovision had significantly worse stereoacuity compared with control subjects (P <.05). Median stereoacuity values were 100 seconds of arc for patients with low anisometropia, 150 seconds of arc for patients with moderate anisometropia, and 40 seconds of arc for control subjects. A larger proportion of patients with moderate anisometropia failed the Worth-4 dot test at distance than control subjects (z = 2.619; P =.009). CONCLUSIONS: Reduced stereoacuity and an absence of foveal fusion in adults with longstanding surgical monovision suggest continued susceptibility of the binocular visual system to anomalous binocular experience.
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Anisometropía/fisiopatología , Percepción de Profundidad/fisiología , Visión Monocular/fisiología , Adulto , Humanos , Queratomileusis por Láser In Situ , Láseres de Excímeros , Persona de Mediana Edad , Queratectomía Fotorrefractiva , Presbiopía/cirugía , Visión Binocular/fisiologíaRESUMEN
Polymorphic B cell lymphoma and diffuse B cell lymphoproliferation associated with Epstein-Barr virus infection is increasingly reported in immunodeficient patients. Accurate diagnosis of these pathologies is essential because the appropriate treatment regimens for the patients in question differ from those for patients with other lymphoproliferative diseases. Two complementary techniques are currently used in the diagnosis and characterization of Epstein-Barr virus-associated B cell lymphomas and diffuse B cell lymphoproliferation. Immunofluorescence allows specific detection of Epstein-Barr nuclear antigens in lymphomatous tissue. Molecular hybridization with the Bam H1-W and/or Bam H1-NJ probes confirms the presence of the Epstein-Barr virus genome in tumour cells. The Bam H1-NJ probe is also useful in determining the clonality of the tumour and the replication mode, episomal or linear, of the viral genome. The polymerase chain reaction method allows detection of the Epstein-Barr virus genome within 24 h in these tumours and is more sensitive.
RESUMEN
Sickle cell anemia (SCA) remains associated with high risks of morbidity and early death. Allogeneic hematopoietic SCT (HSCT) is the only curative treatment for SCA. We report our experience with transplantation in a group of patients with the non-Black African variant and the Black African variant of SCA. This study included 40 consecutive SCA patients (13 patients with the non-Black African variant and 27 with the Black African variant) who underwent BM transplantation from HLA-identical sibling donors between June 2004 and May 2013, following a myeloablative-conditioning regimen. All patients obtained sustained engraftment. One patient (non-Black African variant) became a stable mixed chimera with 25% donor cells more than 6 years after transplantation. The probabilities of survival, SCA-free survival and TRM at 5 years after transplant were 91%, 91% and 9%, respectively. All surviving patients remained free of any SCA-related events after transplantation. Our results confirm that it is possible to offer a greater than 90% chance of cure to children with SCA. HSCT should be considered the standard of care for who have an HLA-identical donor, before complications result from the sickling of RBC.