RESUMEN
OBJECTIVE: Adrenergic receptors belong to the G protein-coupled receptor family and are one of the important targets of modern drug therapy. Dexmedetomidine (DEX) is a highly selective agonist of alpha2 receptor, a member of the adrenergic receptor family, which are widely found in immune tissues and which mediate the biological behaviour of the inflammatory immune system. This review mainly summarizes the role of DEX in immune tissue and inflammation-related diseases, to provide a theoretical basis for clinical treatment. MATERIALS AND METHODS: We searched the PUBMED, EMBASE, and Cochrane libraries separately to obtain published literature on DEX related to immune tissue and inflammatory diseases. The mesh (dexmedetomidine replaces DEX, microglia, astrocytes, spleen, marrow, lymph nodes) and their corresponding keywords used for the searches, and no time limit for retrieval. The latest search was conducted on July 1, 2022. RESULTS: By reading a lot of relevant literature, we found that DEX reduces the inflammatory response of brain tissue by interfering with microglia and astrocytes. DEX can regulate the expression of CD40 and CD86 markers on the surface of splenocytes and reduce the secretion of inflammatory cytokines by splenocytes. In addition, we found that DEX reduced inflammation-related diseases such as neuroinflammation, myocarditis, liver cirrhosis, osteoarthritis, upper respiratory tract infection, pancreatitis, spinal tuberculosis, pulpitis, colon inflammation and rheumatoid arthritis, and improved prognosis. CONCLUSIONS: DEX has anti-inflammatory and improved prognosis in many inflammatory related diseases and is expected to become a targeted drug for the treatment of inflammatory diseases.
Asunto(s)
Dexmedetomidina , Humanos , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Microglía/metabolismo , Citocinas/metabolismo , Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/metabolismoRESUMEN
BACKGROUND: Recent publications have suggested that human epidermal growth factor receptor 2 (HER2)-negative breast cancers with "weak" estrogen receptor (ER)/progesterone receptor (PR) expression levels by immunohistochemical (IHC) analysis were considered as the triple-negative (TN) subtype. This study aimed to evaluate the overall survival (OS), disease-free survival rates (DFS), and disease-specific survival (DSS) based on ER and PR expression levels into one of three groups, ER and PR <1%, ER and PR 1%-20%, and ER or PR >20% by hormone therapy. METHODS: Medical records of 3353 breast cancer patients treated from 2006 to 2013 were retrospectively reviewed. Tumor characteristics, type of treatment, OS, DFS and DSS were evaluated among the three patient groups. RESULTS: Regarding OS, there were significant differences according to the received hormone therapy in the different groups: ER and PR <1% (P = 0.972), ER and PR 1%-20% (P = 0.264), and ER or PR >20% (P = 0.014). Regarding DFS and DSS, there were also significant differences in the different groups: ER and PR <1% (P = 0.611, 0.766), ER and PR 1%-20% (P = 0.847, 0.629), and ER or PR >20% (P = 0.031, 0.002). CONCLUSIONS: In HER2 negative breast cancer patient with hormone therapy, ER and PR expression level of 1%-20% has similar survival outcome to the ER and PR expression level of <1% by IHC analysis.
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Receptor ErbB-2/metabolismo , Receptores de Estrógenos/biosíntesis , Receptores de Progesterona/biosíntesis , Neoplasias de la Mama Triple Negativas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Terapia de Reemplazo de Hormonas/métodos , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Taiwán/epidemiología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Adulto JovenRESUMEN
Objective: To investigate the dynamic expression of placenta growth factor (PlGF) in the lungs and its role in paraquat-induced pulmonary fibrosis and to evaluate the effect of ACEI captopril and AT (1) -receptor blocker losartan on paraquat-induced pulmonary fibrosis. Methods: 84 adult healthy female Sprague-Dawley (SD) rats were randomly divided into four groups of different treatments designated as: Control, PQ alone (PQ) , captopril treatment, losartan treatment. Each group was divided into three subgroups of seven animals each. The animals were killed at either 7, 14 or 28 days after PQ administration. The rats in PQ group, treatment group were treated intragastrically (ig) with PQ (40 mg/kg) and the rats in control group were treated with the same dose of saline at the beginning of the experiment. The treatment group received Captopril (60 mg/kg; ig) or Losartan (10 mg/kg; ig) once a day respectively after PQ administration and the other two groups received saline. At the given timepoint, animals were sacrificed and lungs were harvested. A semiquantitative assay of histological examination, hydroxyproline in lung tissues were used to determine the severity of alveolitis and fibrosis. RT-PCR and immunohistochemistry were used to detect the mRNA and protein expression of PlGF. Results: Inflammatory cell infiltration and fibrotic scores were more prominent in the model group, hydroxyproline contents in lung tissue were significantly increased after PQ administration compared to the control group. Captopril, losartan apparently attenuated the degree of lung injury and pulmonary fibrosis. On 7th, 14th days, the levels of alveolitis in the intervention groups were significantly alleviated as compared with the model group (P<0.05) . On 28th days, the levels of pulmonary fibrosis in the intervention groups were significantly alleviated as compared with model group (P<0.05) . The hydroxyproline contents in the intervention groups were significantly decreased as compared with model group (P<0.01) . PlGF mRNA on day 7, 14, 28 (1.28±0.29vs0.10±0.01ã0.80±0.07vs0.10±0.01ã0.65±0.13vs0.10±0.01) in the PQ group were all upregulated as compared with that of the control group. PlGF mRNA on day 7, 14, 28 in the captopril and Losartan intervention groups were significantly decreased (0.94±0.04ã0.71±0.09ã0.52±0.24 and 0.80±0.12ã0.66±0.11ã0.51±0.03) . PlGF positive expression index on day 7, 14, 28 (2.27±0.34 vs0.13±0.01ã1.78±0.41 vs0.14±0.03ã1.25±0.69 vs0.13±0.01) in the PQ group were all upregulated as compared with that of the control group. PlGF positive expression index on day 7, 14, 28 in the captopril and Losartan treatment groups were significantly decreased (1.53±0.78ã1.17±0.79ã0.97±0.61 and 1.36±0.63ã1.24±0.80ã0.83±0.47) . PlGF positive expression index on day 7 in the two intervention groups were significantly decreased, as compared with PQ group (P<0.05) . Conclusion: PlGF may plays an important role in the development of pulmonary fibrosis following paraquat-induced lung injury in rats. Captopril and losartan had an inhibitory effect on paraquat-induced pulmonary fibrosis, and the effect may be due to inhibition of angiotensin II and, in part, be associated with reduction in PlGF.
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Captopril/farmacología , Losartán/farmacología , Paraquat/toxicidad , Factor de Crecimiento Placentario/metabolismo , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Animales , Femenino , Pulmón/metabolismo , Pulmón/patología , Factor de Crecimiento Placentario/efectos de los fármacos , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyAsunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Adenocarcinoma/diagnóstico por imagen , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Persona de Mediana Edad , Paclitaxel/uso terapéutico , Tomografía Computarizada por Rayos XRESUMEN
Upregulated expression of nucleolar GTPase nucleostemin (NS) has been associated with increased cellular proliferation potential and tumor malignancy during cancer development. Recent reports attribute the growth regulatory effects of NS protein to its role in facilitating ribosome production. However, the oncogenic potential of NS remains unclear, as imbalanced levels of NS have been reported to exert growth inhibitory effect by modulating p53 tumor-suppressor activity. It also remains in questions if aberrant NS levels might have a p53-independent role in regulation of cell proliferation and growth. In this study, we performed affinity purification and mass spectrometry analysis to explore protein-protein interactions influencing NS growth regulatory properties independently of p53 tumor suppressor. We identified the alternative reading frame (ARF) protein as a key protein associating with NS and further verified the interaction through in vitro and in vivo assays. We demonstrated that NS is able to regulate cell cycle progression by regulating the stability of the ARF tumor suppressor. Furthermore, overexpression of NS suppressed ARF polyubiquitination by its E3 ligase Ubiquitin Ligase for ARF and elongated its half-life, whereas knockdown of NS led to the decrease of ARF levels. Also, we found that NS can enhance NPM stabilization of ARF. Thus, we propose that in the absence of p53, ARF can be stabilized by NS and nucleophosmin to serve as an alternative tumor-suppressor surveillance, preventing potential cellular transformation resulting from the growth-inducing effects of NS overexpression.
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Proteínas Portadoras/antagonistas & inhibidores , Proteínas de Unión al GTP/fisiología , Proteínas Nucleares/fisiología , Proteína p14ARF Supresora de Tumor/fisiología , Ubiquitina-Proteína Ligasas/antagonistas & inhibidores , Línea Celular Tumoral , Puntos de Control de la Fase G1 del Ciclo Celular , Proteínas de Unión al GTP/química , Humanos , Proteínas Nucleares/química , Estabilidad Proteica , Estructura Terciaria de Proteína , Proteínas Proto-Oncogénicas c-mdm2/fisiología , Proteína p14ARF Supresora de Tumor/química , Proteína p53 Supresora de Tumor/fisiologíaAsunto(s)
Atrofia Muscular/etiología , Neoplasias de la Columna Vertebral/complicaciones , Neoplasias de la Columna Vertebral/secundario , Dolor de Espalda/etiología , Neoplasias de la Mama/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Atrofia Muscular/diagnóstico , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/etiología , Compresión de la Médula Espinal/diagnóstico , Compresión de la Médula Espinal/etiología , Neoplasias de la Columna Vertebral/diagnósticoRESUMEN
BACKGROUND: Rituximab has been associated with hepatitis B virus reactivation (HBV-R). However, the characteristics and scope of this association remain largely undefined. METHODS: We completed a comprehensive literature search of all published rituximab-associated HBV-R cases and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) MedWatch database. Literature and FDA cases were compared for completeness, and a meta-analysis was completed. RESULTS: One hundred and eighty-three unique cases of rituximab-associated HBV-R were identified from the literature (n = 27 case reports, n = 156 case series). The time from last rituximab to reactivation was 3 months (range 0-12), although 29% occurred >6 months after last rituximab. Within FDA data (n = 118 cases), there was a strong signal for rituximab-associated HBV-R [proportional reporting ratio = 28.5, 95% confidence interval (CI) 23.9-34.1; Empiric Bayes Geometric Mean = 26.4, 95% CI 21.4-31.1]. However, the completeness of data in FDA reports was significantly inferior compared with literature cases (P < 0.0001). Among HBV core antibody (HBcAb(+)) series, the pooled effect of rituximab-based therapy showed a significantly increased risk of HBV-R compared with nonrituximab-treated patients (odds ratio 5.73, 95% CI 2.01-16.33; Z = 3.33, P = 0.0009) without heterogeneity (χ(2) = 2.12, P = 0.5473). CONCLUSIONS: The FDA AERS provided strong HBV-R safety signals; however, literature-based cases provided a significantly more complete description. Furthermore, meta-analysis of HBcAb(+) series identified a more than fivefold increased rate of rituximab-associated HBV-R.
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Anticuerpos Monoclonales de Origen Murino/efectos adversos , Antineoplásicos/efectos adversos , Virus de la Hepatitis B , Hepatitis B/inducido químicamente , Trastornos Linfoproliferativos/tratamiento farmacológico , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos , Anciano , Anciano de 80 o más Años , Femenino , Hepatitis B/complicaciones , Humanos , Trastornos Linfoproliferativos/complicaciones , Trastornos Linfoproliferativos/virología , Masculino , Persona de Mediana Edad , Recurrencia , Rituximab , Estados Unidos , United States Food and Drug Administration , Adulto JovenAsunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Ampolla Hepatopancreática/patología , Quilotórax/etiología , Neoplasias del Conducto Colédoco/tratamiento farmacológico , Neoplasias del Conducto Colédoco/radioterapia , Traumatismos por Radiación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/administración & dosificación , Terapia Combinada , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Recent data suggest that hepatitis B virus (HBV) reactivation develops in 41% of breast cancer (BC) patients carrying HBV after chemotherapy. Our study aimed to determine the role of preemptive use of lamivudine in BC patients undergoing chemotherapy. PATIENTS AND METHODS: The test group consisted of 11 female patients with BC who were seropositive for hepatitis B surface antigen (HBsAg). Of these, 10 patients were treated in an adjuvant setting and one for metastatic disease. Lamivudine was given from the start of chemotherapy and was maintained until 1 month after the last infusion of chemotherapy. The control group consisted of nine historical BC patients carrying HBV and received similar systemic chemotherapy without preemptive lamivudine. Variables including HBsAg, HBV envelope antigen, anti-HBV envelope antibody, serial serum alanine transaminase (ALT), quantitative HBV viral DNA analysis, and HBV-DNA precore promoter and precore sequence were monitored. Test for emergence of mutant strains, notably nucleotide 550, was performed 6 months after the completion of chemotherapy. RESULTS: All patients tolerated lamivudine well without development of evident HBV reactivation or overt hepatitis. Serum ALT remained unchanged without rebound hepatitis after cessation of chemotherapy and withdrawal of lamivudine. No emergence of lamivudine-selective resistant strain (so-called tyrosine-methionine-aspartate-aspartate mutations) was observed. CONCLUSIONS: Our results encourage preemptive use of lamivudine for prevention of HBV reactivation in patients who need short-term chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B/prevención & control , Lamivudine/administración & dosificación , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Secuencia de Bases , Neoplasias de la Mama/patología , Neoplasias de la Mama/virología , ADN Viral/análisis , Femenino , Estudios de Seguimiento , Hepatitis B/tratamiento farmacológico , Antígenos de Superficie de la Hepatitis B/análisis , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , Monitoreo Fisiológico , Prevención Primaria/métodos , Estudios Prospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Medición de Riesgo , Prevención Secundaria , Pruebas Serológicas , Resultado del TratamientoRESUMEN
Malignancy-related thromboembolism, so-called Trousseau's syndrome, can present as acute cerebral infarction, non-bacterial thrombotic endocarditis (NBTE) and migratory thrombophlebitis. It is usually attributed to a cancer-related hypercoagulable state, chronic disseminated intravascular coagulopathy (DIC), or tumour embolism. We report on two patients with adenocarcinoma of the colon and cholangiocarcinoma who developed widespread thromboembolism during disease progression. Both did poorly despite aggressive institution of anticoagulation therapy. These cases emphasize that cerebral infarction or refractory thromboembolism in cancer-treated patients should prompt investigation for recurrent or metastatic disease or progression of the underlying malignancy. Optimal treatment remains to be established.
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Adenocarcinoma/complicaciones , Neoplasias de los Conductos Biliares/complicaciones , Conductos Biliares Intrahepáticos , Colangiocarcinoma/complicaciones , Neoplasias del Colon/complicaciones , Embolia Intracraneal/etiología , Adulto , Femenino , Humanos , Embolia Intracraneal/patología , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
We recently treated a patient with severe aplastic anaemia (SAA) who also had chronic hepatitis B virus (HBV) infection. The HBV serological status at the time of diagnosis of SAA was HBsAg(+) and HBeAg(+). Subsequent analysis of the precore region of HBV DNA showed wild-type. He received anti-thymocyte globulin (ATG) and cyclosporin A (CsA) therapy twice. After each course of ATG infusion and during CsA therapy he developed lymphopenia for 1 and 2.5 months, respectively. His serum alanine aminotransferase (ALT) became normalized during the period of lymphopenia, but the serum HBV viral load increased. When his peripheral lymphocytes count recovered, his ALT became elevated again. Lamivudine was effective to normalize his elevated ALT and suppress viral replication. The phenomenon observed in this case supports the prevailing notion that hepatitis B flare-up in HBV carriers after chemotherapy is caused by an immune-mediated mechanism. Meanwhile, this is the first documented case of SAA who developed HBV reactivation upon recovery of lymphopenia after immunosuppressive therapy. This also highlights the necessity of pre-emptive therapy with lamivudine in SAA/HBsAg(+) patients to receive immunosuppressive therapy with ATG/CsA.
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Anemia Aplásica/complicaciones , Anemia Aplásica/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Inmunosupresores/uso terapéutico , Adulto , Anemia Aplásica/inmunología , Suero Antilinfocítico/efectos adversos , Suero Antilinfocítico/uso terapéutico , Antivirales/uso terapéutico , Portador Sano/tratamiento farmacológico , Portador Sano/inmunología , Ciclosporina/efectos adversos , Ciclosporina/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/inmunología , Humanos , Inmunosupresores/efectos adversos , Lamivudine/uso terapéutico , Masculino , RecurrenciaRESUMEN
A 34-year-old man was diagnosed as having solitary testicular plasmacytoma. He had received palliative radiotherapy, several combined chemotherapies including CHOP chemotherapy (vincristine, cyclophosphamide, Adriamycin, and prednisone), MP (melphalan and prednisone) and M-2 protocol (melphalan, prednisone, vincristine, carmustine, and cyclophosphamide), and interferon therapy as 3 million units subcutaneous injection three times a week for 1 year. Extensive bone plasmacytoma developed 7 years later without bone marrow involvement. We suggest that early use of combined chemoradiotherapy and high-dose chemotherapy with autologous stem cell support should be investigated in patients with testicular plasmacytoma with dissemination.
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Plasmacitoma/secundario , Neoplasias Craneales/metabolismo , Neoplasias Craneales/patología , Neoplasias Testiculares/patología , Adulto , Antineoplásicos Alquilantes/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Médula Ósea/patología , Carmustina/uso terapéutico , Terapia Combinada , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Masculino , Melfalán/uso terapéutico , Células Plasmáticas/patología , Plasmacitoma/tratamiento farmacológico , Plasmacitoma/radioterapia , Plasmacitoma/cirugía , Prednisona/uso terapéutico , Neoplasias Craneales/diagnóstico por imagen , Neoplasias Craneales/radioterapia , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/cirugía , Tomografía Computarizada por Rayos X , Vincristina/uso terapéuticoRESUMEN
We describe an 82-year-old man with undiagnosed chronic lymphocytic leukemia (CLL) who presented with acute swelling of the thyroid goiter. Subsequent thyroid aspirate and blood culture yielded group B Salmonella thyroid abscess with septicemia. Infectious complications are the major cause of morbidity and mortality in patients with CLL since most of them can be timely detected and few can arise from innocent-looking lesions.
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Leucemia Linfocítica Crónica de Células B/complicaciones , Infecciones por Salmonella/patología , Salmonella typhimurium , Tiroiditis Supurativa/microbiología , Tiroiditis Supurativa/patología , Absceso/complicaciones , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Infecciones por Salmonella/complicaciones , Tiroiditis Supurativa/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
Pyomyositis is a rare complication of chemotherapy. A 35-year-old male patient with myelodysplastic syndrome developed Stenotrophomonas maltophilia bacteremia shortly after chemotherapy, and Stenotrophomonas maltophilia-related pyomyositis was encountered after recovery from neutropenia. He recovered completely after surgical drainage and a protracted course of antibiotic treatment. It is postulated that subclinical myopathy, immunosuppression secondary to the malignancy, or chemotherapeutic drugs may predispose to pyomyositis. Early recognition of this unusual complication in a cancer patient undergoing chemotherapy can prevent further catastrophes.
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Antineoplásicos/efectos adversos , Miositis/inducido químicamente , Sepsis/inducido químicamente , Stenotrophomonas maltophilia , Adulto , Diagnóstico Diferencial , Humanos , Pierna/patología , Imagen por Resonancia Magnética , Masculino , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/tratamiento farmacológico , Miositis/diagnóstico , Miositis/terapia , Infecciones Oportunistas , Sepsis/diagnóstico , Sepsis/terapiaRESUMEN
Tumor lysis syndrome (TLS) is a well recognized complication of chemotherapy and radiotherapy for leukemia, lymphoma as well as rapidly growing malignancies. Less described is the occurrence of TLS following steroid therapy alone. Herein, we report on a 32-year-old male with myelodysplastic syndrome, characterized by refractory anemia with excess blasts in transformation, who developed acute oliguric renal failure 12 hours after methylprednisolone 1.0 g for presumed autoimmune thrombocytopenia. Laboratory investigations revealed typical findings of TLS, including hyperkalemia, marked hyperuricemia, hyperphosphotemia, hypocalcemia and urine uric acid to creatinine ratio 1.8 (> 1.0). Long hemodialysis (8 hours) was initiated for 3 consecutive sessions. Renal function recovered 1 week later. This case high-lights that single-dose steroid administration in a patient with hematological malignancy may cause the potential life-threatening complications of TLS. Prophylactic management prior to the use of steroid therapy for a variety of purposes is absolutely required in high-risk patients.
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Lesión Renal Aguda/inducido químicamente , Glucocorticoides/efectos adversos , Metilprednisolona/efectos adversos , Síndromes Mielodisplásicos/complicaciones , Síndrome de Lisis Tumoral/etiología , Adulto , Humanos , MasculinoRESUMEN
BACKGROUND: A point mutation from G to A at nucleotide (nt) 1896 of the precore region of hepatitis B virus (HBV) DNA has been shown to be associated with fulminant and severe hepatitis. Further studies have suggested that this point mutation, together with additional mutations in the precore promoter, is probably linked to the reactivation of HBV in patients undergoing cytotoxic chemotherapy. Taiwan is an area with a high prevalence of HBV where hepatitis B flare-up has become a serious problem of HBV carriers who must rely on chemotherapy to treat their diseases. The purpose of this study was to examine if nt 1896 mutation was also present in Chinese patients in Taiwan who developed severe liver disease after chemotherapy. MATERIALS AND METHODS. Thirteen HBV carrier patients, including eight patients with lymphoma, two with germ cell tumors, two with breast carcinomas, and one with acute myeloid leukemia, received chemotherapy in the authors' hospital from February 1994 to May 2000. They all received steroid-containing regimens or antiemetics during chemotherapy. These patients were monitored closely for the development of severe hepatitis during or after chemotherapy. Their sera were harvested at different times for direct sequencing of the polymerase chain reaction products of the precore region of HBV DNA. RESULTS: Six of the 13 patients developed severe hepatitis with a fulminant course during or after the completion of chemotherapy. A point mutation from G to A at nt 1896 was detected in five of these six patients. Among those five patients, four had additional precore mutations. The other patient did not have the nt 1896 mutation but had mutations at nt 1835 (A to C). None of the other seven patients lacking the precore nt 1896 mutation developed severe hepatitis flare-up. One of those seven patients who developed moderate elevation of alanine aminotransferase (ALT) without hyperbilirubinemia did have precore mutations other than nt 1896. None of the other six patients had mutations over the precore region. CONCLUSIONS: Nucleotide mutation of the precore region, notably at position 1896, is associated with reactivation of HBV with a fulminant course during or after chemotherapy. The current data, together with other investigators' findings, suggest that patients who are HBV carriers with HBV envelope antigen (HBeAg) (-)/anti-HBV envelope antibody (Anti-HBe)(+) status should be assayed to determine if they carry mutant HBV before chemotherapy. Prophylactic use of lamivudine is strongly recommended for patients who carry mutant HBV at precore region, especially at nt 1896 (G to A), before and during chemotherapy.
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Virus de la Hepatitis B/genética , Hepatitis B/virología , Activación Viral/genética , Adulto , Anciano , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Hepatitis B/epidemiología , Hepatitis B/etiología , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/crecimiento & desarrollo , Virus de la Hepatitis B/fisiología , Humanos , Linfoma/complicaciones , Linfoma/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Mutación , Taiwán/epidemiologíaRESUMEN
Pulmonary complications are frequently encountered in patients with hematological malignancy. The optimal therapeutic decision including open lung biopsy (OLB) for such patients is uncertain. We herein examine the clinical impact of OLB on these patients. Seven patients with progressively diffuse pulmonary infiltrates despite aggressive medical treatment were examined. The underlying diseases, prior treatment for presumptive pneumonia, the change in therapeutic approach after operation, and clinical outcome were reviewed retrospectively. Diffuse pulmonary infiltrates were caused by infection in two patients and by noninfectious etiology such as alveolar proteinosis, idiopathic interstitial pneumonitis, leukemic involvement, and drug-induced alveolar damage in the others. Four patients who had serious underlying hematologic diseases such as myelodysplastic syndrome, acute and chronic myeloid leukemia, and T cell lymphoma died. Three patients with acute lymphoid leukemia survived. In two of these three, change of therapeutic strategies after OLB was created for the survival. OLB in patients with hematological malignancy may be useful in selected patients with a treatable hematologic disease who have treatable underlying causes of the pulmonary infiltrate.
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Biopsia/métodos , Neoplasias Hematológicas/patología , Enfermedades Pulmonares/diagnóstico , Pulmón/patología , Adolescente , Adulto , Causas de Muerte , Terapia Combinada , Femenino , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Pulmón/microbiología , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Acute aortic dissection may have variable presentations, making the diagnosis clinically challenging. Although fever is a common accompanying feature, it rarely dominates the clinical setting. We report the case of a patient who sustained a prolonged spiking fever with unknown origin following acute aortic dissection. The case serves as a reminder that prolonged fever may be the principal residual sequelae after acute aortic dissection or one of the protean clinical manifestations of painless aortic dissection.
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Aneurisma de la Aorta/complicaciones , Disección Aórtica/complicaciones , Fiebre de Origen Desconocido/etiología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
The dynamics of cell cycle regulation were investigated during in vitro erythroid proliferation and differentiation of CD34(+) cord blood cells. An unusual cell cycle profile with a majority of cells in S phase (70.2%) and minority of cells in G1 phase (27.4%) was observed in burst-forming unit-erythrocytes (BFU-E)-derived erythroblasts from a 7-day culture of CD34(+) cells stimulated with interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), Steel factor, and Epo. Terminal erythroid differentiation was accompanied by a rapid increase of G0/G1 phase cells. Expression of cyclin E and cyclin-dependent kinase 2 (cdk2) correlated with the proportion of S phase cells. Cyclin D3 was moderately up-regulated during the proliferation phase, and both cyclin E and D3 were rapidly down-regulated during terminal differentiation. This suggests that the high proliferation potential of erythroblasts is associated with temporal up-regulation of cyclin E and cdk2. (Blood. 2000;96:3985-3987)
Asunto(s)
Quinasas CDC2-CDC28 , Proteínas de Ciclo Celular/metabolismo , Células Madre Hematopoyéticas/citología , Técnicas de Cultivo de Célula , Ciclo Celular/efectos de los fármacos , Ciclo Celular/fisiología , Proteínas de Ciclo Celular/efectos de los fármacos , Proteínas de Ciclo Celular/fisiología , Diferenciación Celular/efectos de los fármacos , Quinasa 2 Dependiente de la Ciclina , Quinasas Ciclina-Dependientes/metabolismo , Quinasas Ciclina-Dependientes/fisiología , Ciclinas/efectos de los fármacos , Ciclinas/metabolismo , Ciclinas/fisiología , Citocinas/farmacología , Células Precursoras Eritroides/citología , Sangre Fetal/citología , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/fisiología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Our previous study demonstrated that transduction of murine embryonic stem (ES) cells with a human erythropoietin (Epo) receptor (R) cDNA resulted in enhanced erythropoiesis in developing embryonic bodies (EBs). To address possible mechanisms of gene regulation, we compared gene expression between hEpoR cDNA-transduced ES (ES-hEpoR) cells and parental ES cells during in vitro differentiation induced by withdrawal of leukemia inhibitory factor (LIF) and cultured in the absence of Epo using differential display reverse transcriptase-polymerase chain reaction (DDRT-PCR). A total of 48 differentially expressed cDNA fragments were found; 12 were sequenced and five were confirmed by Northern blot analysis to be up- or down-regulated in ES-hEpoR cells during differentiation compared to parental ES cells. In a GenBank search of the five putatively regulated cDNA fragments, two fragments shared high sequence homology to two known genes: the Surf-6 gene and the gene for calcyclin binding protein. Northern blot analysis demonstrated that 2.5-kb and 0.3-kb transcripts of the Surf-6 gene were expressed in undifferentiated ES-hEpoR and parental ES cells at a low level, but this expression was enhanced from day 2 to 14 of differentiation after withdrawal of LIF and culture in the presence of Epo. Furthermore, the enhanced expression of these two transcripts was also noticed in EML-C1 cells, a murine multipotential hematopoietic cell line that has erythroid differentiation potential in response to Epo. In summary, our results demonstrate that Surf-6 gene expression is regulated during differentiation of hematopoietic stem/progenitor cells in response to Epo, suggesting a possible role for Surf-6 gene in erythropoiesis.