RESUMEN
The intensity of the heaviest extreme precipitation events is known to increase with global warming. How often such events occur in a warmer world is however less well established, and the combined effect of changes in frequency and intensity on the total amount of rain falling as extreme precipitation is much less explored, in spite of potentially large societal impacts. Here, we employ observations and climate model simulations to document strong increases in the frequencies of extreme precipitation events occurring on decadal timescales. Based on observations we find that the total precipitation from these intense events almost doubles per degree of warming, mainly due to changes in frequency, while the intensity changes are relatively weak, in accordance to previous studies. This shift towards stronger total precipitation from extreme events is seen in observations and climate models, and increases with the strength - and hence the rareness - of the event. Based on these results, we project that if historical trends continue, the most intense precipitation events observed today are likely to almost double in occurrence for each degree of further global warming. Changes to extreme precipitation of this magnitude are dramatically stronger than the more widely communicated changes to global mean precipitation.
RESUMEN
Fifty-one cases of acquired immunodeficiency syndrome (AIDS)-related primary brain lymphomas (AR-PBL) were investigated for clinical characteristics; human immunodeficiency virus (HIV)-associated disorders; histopathologic features; immunophenotype; Epstein-Barr virus (EBV) infection; and, when frozen tissue was available, oncogene rearrangements. AR-PBL occurred late in the course of AIDS and were usually associated with other systemic or cerebral disorders and with a low level of CD4 lymphocytes. All cases were high grade lymphomas according to the Working Formulation or updated Kiel classification, and often displayed a multifocal pattern. Thirty cases were classified as immunoblastic with plasmacytic differentiation, 18 cases were large cell lymphomas with an immunoblastic component or centroblastic polymorphic lymphomas, and 2 were small noncleaved non-Burkitt lymphomas (Working Formulation). This latter category is classified as Burkitt's-like lymphoma in the REAL nomenclature. One case could not be classified because of necrosis. AR-PBL showed a high level expression of activation and adhesion molecules. The presence of EBV was detected in most cases, and, when PCR was used, this was a constant finding. bcl-2 oncoprotein and latent membrane protein-1 (LMP-1) were strongly expressed. None of the tested cases expressed p53, or were rearranged for bcl-2 or c-myc oncogenes. This study confirms the immunophenotypic specificity of AR-PBL, which may reflect the special immune status of the brain.
Asunto(s)
Neoplasias Encefálicas/patología , Linfoma Relacionado con SIDA/patología , Adulto , Antígenos Virales/metabolismo , Neoplasias Encefálicas/metabolismo , Antígenos Nucleares del Virus de Epstein-Barr/metabolismo , Femenino , Genotipo , Herpesvirus Humano 4/genética , Humanos , Inmunohistoquímica , Inmunofenotipificación , Hibridación in Situ , Linfoma Relacionado con SIDA/metabolismo , Masculino , Persona de Mediana Edad , Oncogenes , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-myc , ARN Viral/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteínas de la Matriz Viral/metabolismoRESUMEN
We report the natural history of 17 brain lymphomas (11 primary, 6 disseminated) from a post-mortem series of 130 patients with AIDS. Primary lymphomas appeared lately in the course of AIDS. They were often associated with a severe T-cell immunodepression and with more frequent opportunistic disorders than disseminated lymphomas. Associated Kaposi's sarcomas were surprisingly frequent. All patients presented with neurological manifestations. Heterogeneous features were seen at CT examination. The CSF was abnormal in 12/13 cases, with an increase of protein contents and secretion of immunoglobulins; it contained activated lymphocytes in 5/6 cases of disseminated lymphomas, and malignant cells in only one case. Cellular density never exceeded 8/mm3 for primary lymphomas, and the lymphocytes were considered normal. The pre-mortem diagnosis of cerebral lymphomas was made in five patients, with a time lapse of 1 to 7 months between the first neurological symptoms and death, and of 5 to 30 days between the diagnosis and death. Cerebral biopsy was diagnostic in 4 cases of primary cerebral lymphomas. In only 1/6 patients with disseminated lymphomas, the diagnosis had been made when the patient was still alive, based on CSF and bone marrow lymphomatous infiltrations. The diagnosis of cerebral lymphoma (7 primary, 5 disseminated) was post-mortem in 12 cases. It was made only at microscopic examination in 2/12 cases of primary lymphomas. The histopathological study frequently showed a multicentric involvement, and always an immunoblastic cell type with plasmablastic differentiation and frequent medium size cells. Marked gliosis and significant necrosis were often observed. Neuropathological lesions associated with HIV-1 infection (toxoplasmosis, CMV and HIV-1 encephalitis) were seen in 8 cases with primary lymphomas.
Asunto(s)
Neoplasias Encefálicas/diagnóstico , Linfoma Relacionado con SIDA/diagnóstico , Sarcoma de Kaposi/etiología , Adulto , Neoplasias Encefálicas/etiología , Humanos , Linfoma Relacionado con SIDA/complicaciones , Linfoma Relacionado con SIDA/patología , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/diagnóstico , Enfermedades del Sistema Nervioso/etiología , Sarcoma de Kaposi/diagnósticoRESUMEN
In acquired immunodeficiency, B-cell proliferation is usually associated with Epstein-Barr virus (EBV), implying the impairment of the normal control of EBV and EBV-infected cells. It has been assumed that EBV infection is latent in lymphoproliferative disorders. In order to determine the type of latency and to investigate whether any lymphoproliferative disorders enter into the lytic cycle, we analyzed the expression of latent and replicative EBV genes in 9 post-transplant lymphoproliferative disorders (PTLD) and in 23 EBV-positive AIDS-related non-Hodgkin's lymphomas (AR-NHL). The PTLD cases were categorized into polyclonal or monoclonal polymorphic tumors and monoclonal monomorphic tumors. The AR-NHL cases included large-cell/immunoblastic (LC/IB) and Burkitt's lymphoma (BL) groups. We demonstrated that varying patterns of latent-viral-gene expression are exhibited showing the 3 forms of latency. Polymorphic PTLD and LC/IB AR-NHL frequently expressed type II or III latency, whereas monomorphic tumors and BL AR-NHL showed type I latency. It is noteworthy that 3 cases of BL AR-NHL expressed latency II form. Induction of lytic cycle highlighted by the expression of BZLF1 occurred in 55.5% of PTLD, 36% of LC/IB and 22% of BL AR-NHL. In contrast, late viral proteins indicating productive cycle were present in 22% of PTLD, 14% of LC/IB, and were absent in BL cases. These data suggest that the impairment of EBV control permits disruption of latency, but the initiation of the lytic cycle may not always lead to viral production.
Asunto(s)
Herpesvirus Humano 4/genética , Linfoma Relacionado con SIDA/genética , Trastornos Linfoproliferativos/genética , Trasplante de Órganos/efectos adversos , Latencia del Virus/genética , Replicación Viral/genética , Expresión Génica , Herpesvirus Humano 4/fisiología , HumanosRESUMEN
We investigated 49 acquired immunodeficiency syndrome-related lymphomas (ARLs) for Epstein-Barr virus (EBV) by Southern blotting and in situ hybridization and, in positive cases, used cryostat immunohistology to compare EBV-latent gene expression (EBV encoded small RNA-1 [EBER-1], EBV nuclear antigen-2 [EBNA-2], latent membrane protein-1 [LMP-1] and host cell immunophenotype (CD11a, CD18, CD54, CD58, CD21, CD23, CD30, CD39, CDw70, immunoglobulin) patterns with those reported in other EBV infections. EBV+ immunoblast-rich/large cell ARLs (n = 22) showed three patterns of latency: broad (EBER+EBNA-2+/LMP-1+; n = 9), reminiscent of a lymphoblastoid cell line phenotype; restricted (EBER+/EBNA-2-/LMP-1-; n = 6), similar to endemic Burkitt's lymphoma; and intermediate (EBER+/EBNA-2-/LMP-1+; n = 7), a pattern rarely described in vitro but seen in certain EBV-related malignancies. EBNA-2 expression was associated with extranodal lymphomas. EBV+ Burkitt-type ARLs (n = 11) usually showed the restricted latency pattern (n = 8), but some expressed the intermediate form (n = 3). Adhesion (CD54, CD58) and activation (CD30, CD39, CDw70) molecule expression varied with morphology (immunoblast-rich/large cell versus Burkitt-type), but was not independently correlated with EBV-positivity. CD30 and LMP-1 expression were associated. ARLs show heterogeneity regarding both the presence of EBV and latency pattern. Comparison of these phenotypically distinct lymphoma groups with known forms of EBV infection provides clues to their possible pathogenesis.
Asunto(s)
Antígenos Virales/metabolismo , Proteínas de Unión al ADN/metabolismo , Expresión Génica , Linfoma Relacionado con SIDA/metabolismo , Linfoma no Hodgkin/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas Ribosómicas , Proteínas de la Matriz Viral/metabolismo , Latencia del Virus , Adulto , Anciano , Preescolar , ADN Viral/análisis , Antígenos Nucleares del Virus de Epstein-Barr , Herpesvirus Humano 4/inmunología , Humanos , Inmunofenotipificación , Linfoma Relacionado con SIDA/clasificación , Linfoma Relacionado con SIDA/genética , Linfoma no Hodgkin/clasificación , Linfoma no Hodgkin/genética , Masculino , Persona de Mediana Edad , Hibridación de Ácido Nucleico , Proteínas Oncogénicas Virales/metabolismo , ARN Viral/análisisRESUMEN
Some acquired immunodeficiency syndrome (AIDS)-related lymphomas (ARLs) are infected with Epstein-Barr virus (EBV), although the frequency and importance of this association is disputed. Using paraffin section RNA in situ hybridization (ISH) with digoxigenin-labeled riboprobes, we screened 16 central nervous system (CNS) non-Hodgkin's lymphomas (NHLs), 101 systemic NHLs, and 11 Hodgkin's disease cases arising in human immunodeficiency virus-seropositive individuals for EBV-encoded small RNA (EBER 1) expression, an EBV gene product transcribed in abundance during latent infection. Tumor cells contained EBV in 85 of 128 ARLs (66%), but infection rates differed with lymphoma type. EBER 1 was expressed in tumor cells in 11 of 11 Hodgkin's disease cases (100%), 15 of 16 CNS NHLs (94%), and 46 of 60 systemic immunoblast-rich/large-cell lymphomas (77%), but in only 12 of 35 Burkitt-type (small noncleaved cell) (34%) and 1 of 6 monomorphic centroblastic (diffuse large noncleaved cell) (17%) lymphomas. In most EBV-positive ARLs, all recognizable viable tumor cells expressed EBER 1. We conclude that (1) EBV infects tumor cells in all AIDS-related Hodgkin's disease cases, in virtually all primary CNS ARLs, and in most systemic immunoblast-rich/large-cell ARLs; (2) only a minority of Burkitt-type and monomorphic centroblastic lymphomas are associated with EBV; and (3) EBER-ISH is ideal for the histopathologic detection of latent EBV in routine tissue specimens.
Asunto(s)
Herpesvirus Humano 4/genética , Hibridación in Situ , Linfoma Relacionado con SIDA/microbiología , ARN Viral/análisis , Infecciones Tumorales por Virus/microbiología , Linfocitos B/patología , Neoplasias Encefálicas/microbiología , Neoplasias Encefálicas/patología , Neoplasias del Sistema Nervioso Central/microbiología , Neoplasias del Sistema Nervioso Central/patología , Digoxigenina , Seropositividad para VIH , Herpesvirus Humano 4/aislamiento & purificación , Enfermedad de Hodgkin/microbiología , Enfermedad de Hodgkin/patología , Humanos , Linfoma Relacionado con SIDA/patología , Linfoma no Hodgkin/microbiología , Linfoma no Hodgkin/patología , Infecciones Tumorales por Virus/patologíaRESUMEN
Calcific emboli from a calcific aortic stenosis is an uncommon event, usually following local trauma, as from cardiac surgery or left heart catheterization or as a sequel to bacterial endocarditis. We report what we believe to be the first case of a spontaneous calcareous emboli demonstrated by cranial computed tomography. In this patient, systemic hypertension and mild aortic insufficiency may have caused increasing mechanical forces acting on the aortic cusps and may have precipitated embolism.
Asunto(s)
Estenosis de la Válvula Aórtica/complicaciones , Calcinosis/complicaciones , Embolia y Trombosis Intracraneal/etiología , Anciano , Calcinosis/etiología , Humanos , Embolia y Trombosis Intracraneal/diagnóstico por imagen , Masculino , Radiografía , UltrasonografíaRESUMEN
Bilateral hypothenar muscular spasm ("dimpling") was discovered in a 62 year-old man. The spasms consisted of recurrent arrhythmic contractions of the palmaris brevis muscle. E.M.G. showed no signs of denervation but the contractions could be stopped by infiltration of the ulnar nerve by xylocaine. Apparently, this syndrome has previously been reported in only two cases. Its clinical and electromyographic characteristics are similar to hemifacial spasm. Compression of the ulnar nerve after its division at the wrist could be a cause.
Asunto(s)
Mano , Músculos/fisiopatología , Espasmo/diagnóstico , Diagnóstico Diferencial , Electromiografía , Músculos Faciales/fisiopatología , Dedos , Humanos , Masculino , Persona de Mediana Edad , Músculos/inervación , Síndromes de Compresión Nerviosa/fisiopatología , Espasmo/etiología , Espasmo/fisiopatología , Nervio Cubital/fisiopatologíaRESUMEN
A 58 year old man was admitted with a pseudo-coronary pain. Cardiological investigations (ECG, chest X-ray, enzymes) were normal. Pain however was exacerbated by movement, coughing and pressure over T4 to T10 vertebrae. On the 4th day, the patient developed a weakness of the right lower limb which worsened 15 days later. On examination there were in the right lower limb a combination of central (Babinski sign) and peripheral signs (diminished deep reflexes, loss of sensation to all modalities ipsilateral to the paralysis). Metrizamide myelography was within normal limits. Spinal angiography revealed a dural arteriovenous fistula draining into spinal veins, at the level of T5. Following the removal of the fistula, the pain disappeared and the other symptoms and signs improved.