RESUMEN
BACKGROUND: Microchimerism is defined as a stable presence of low numbers of cells derived from a different individual due to cell transfer between twins or between mother and fetus during pregnancy. OBJECTIVE: Fetal cells in the organism of the mother (FMc) are postulated to play a role in autoimmune diseases. Psoriasis is a disease which has an autoimmune component, but no study on microchimerism in this disease has been reported. METHODS: The easiest way to detect microchimerism is to look for male cells in blood or other tissues of a woman who previously delivered a son. Here, we looked for the presence of male cells in mononuclear cell subpopulations from peripheral blood and in skin samples of women with psoriasis and of healthy women. RESULTS: We detected FMc in similar proportions of patients and controls in CD4+, CD8+ and CD34+ cells, whereas in CD34- cells they were present in higher fraction of controls, and similar but non-significant difference was observed in CD19+ cells. No microchimeric cells were detected in patients' skin samples, both from affected and non-affected skin, or in skin tissue from healthy control individuals. CONCLUSION: Our result does not prove the involvement of microchimerism in the aetiology of psoriasis.
Asunto(s)
Antígenos CD34/inmunología , Quimerismo , Feto/metabolismo , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Adulto JovenRESUMEN
BACKGROUND: The interleukin-17 cytokine family plays a central role in psoriasis pathogenesis. OBJECTIVES: To evaluate the efficacy and safety of brodalumab, a human anti-interleukin-17 receptor antibody, in treating patients with moderate-to-severe plaque psoriasis. METHODS: In this phase III, double-blind, placebo-controlled study (NCT01708590; AMAGINE-1), adult patients in the U.S.A., Canada and Europe were randomized to brodalumab (140 or 210 mg) or placebo every 2 weeks (Q2W), with an additional dose at week 1, for a 12-week induction phase. At week 12, patients receiving brodalumab who achieved static Physician's Global Assessment 0 or 1 (sPGA success) were rerandomized to the placebo or induction dose. After week 16, patients with sPGA ≥ 3 were re-treated with the induction dose. After ≥ 12 weeks of retreatment, patients with sPGA 2 for ≥ 4 weeks or sPGA ≥ 3 were rescued with brodalumab 210 mg Q2W. At week 12, patients randomized to brodalumab with sPGA ≥ 2 or placebo received brodalumab 210 mg Q2W. Coprimary end points were the percentage of patients with ≥ 75% improvement in Psoriasis Area and Severity Index score (PASI 75) and sPGA success at week 12. RESULTS: There were 661 patients randomized: 220 placebo, 219 brodalumab 140 mg and 222 brodalumab 210 mg. At week 12, 60% (140 mg) and 83% (210 mg) vs. 3% (placebo) achieved PASI 75, and 54% (140 mg) and 76% (210 mg) vs. 1% (placebo) achieved sPGA success. The safety profile was considered acceptable. CONCLUSIONS: Brodalumab therapy resulted in significant clinical benefit and an acceptable safety profile in patients with moderate-to-severe plaque psoriasis.
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Anticuerpos Monoclonales/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Psoriasis/tratamiento farmacológico , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Trastornos de Ansiedad/prevención & control , Biomarcadores/metabolismo , Trastorno Depresivo/prevención & control , Fármacos Dermatológicos/efectos adversos , Método Doble Ciego , Esquema de Medicación , Sustitución de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Psoriasis/psicología , Retratamiento , Resultado del TratamientoAsunto(s)
Acantoma/diagnóstico , Población Negra , Neoplasias Cutáneas/diagnóstico , Piel/patología , Adulto , Biopsia , Femenino , Humanos , MusloRESUMEN
To assess the efficacy of an original DAC-7 regimen: daunorubicine (DNR) 60 mg/m2/day, days 1-3; cytarabine (AraC) 200 mg/m2/day, days 1-7; cladribine (2-CdA) 5 mg/m2/day, days 1-5, 400 untreated adult acute myeloid leukemia patients (including 63 with preceding myelodysplastic syndrome), aged 45 (16-60) years were randomized to either DAC-7 (n=200) or DA-7 (without 2-CdA, n=200). The overall CR rate equaled 72% for DAC-7 and 69% for DA-7 arm (P=NS). After a single course of DAC-7 induction, the CR rate equaled 64% and was significantly higher compared to 47% in the DA-7 arm (P=0.0009). Median hospitalization time during the induction was 7 days shorter for DAC-7 compared to the DA-7 group (33 vs 40 days, P=0.002). Toxicity was comparable in both groups. The probability of 3-year leukemia-free survival (LFS) for DAC-7 and DA-7 group equaled 43 and 34%, respectively (P=NS). There was a trend toward higher LFS rate for patients aged >40 years receiving DAC-7 compared with DA-7 regimen (44 vs 28%, P=0.05). This study proves that addition of 2-CdA increases antileukemic potency of DNR+AraC regimen, thus resulting in a higher CR rate after one induction cycle when compared to DA-7, without additional toxicity. It shortens hospitalization time and may improve long-term survival in patients aged >40 years.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Adolescente , Adulto , Cladribina/administración & dosificación , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess the effect of selected clinical and biochemical parameters, with particular consideration of familial hypertension, on the pulse wave velocity (PWV) in young normotensives. SUBJECTS AND METHODS: Seventy voluntary students were enrolled (mean age 22.3+/-2.1 years), 39 men and 31 women, with normal blood pressure. A history was obtained with respect to diabetes mellitus, ischaemic heart disease, lipid disorders and arterial hypertension in the family. The subjects were subdivided into two groups: those with (n = 33) and without (n = 37) a family history of arterial hypertension, and blood pressure and heart rate were measured three times and total cholesterol and its subfractions determined in plasma. The carotid to femoral PWV was measured using an automatic computerized recorder and analysed by the Complior program. RESULTS: The subjects with a family history of arterial hypertension had higher blood pressure levels (systolic and diastolic blood pressure, pulse pressure and mean arterial pressure), as well as mean body mass index and low-density lipoprotein (LDL) cholesterol. The PWV in this group did not differ from that in the subjects without a family history of arterial hypertension (9.69+/-2.8 versus 9.32+/-2.0). However, the PWV was significantly higher in males than females (10.62+/-2.2 versus 7.86+/-1.13, P < 0.0001) and there was a significant positive correlation between male gender and PWV. CONCLUSIONS: Familial arterial hypertension does not significantly affect aortic stiffness in terms of PWV. Male gender in this population of young healthy subjects is one of the most important factors associated with central arterial stiffness.
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Aorta/fisiología , Hipertensión/genética , Registros Médicos , Pulso Arterial , Adulto , Presión Sanguínea , Índice de Masa Corporal , LDL-Colesterol/sangre , Femenino , Humanos , Masculino , Valores de Referencia , Caracteres Sexuales , Factores de TiempoRESUMEN
The clinical and cytogenetic findings of a patient with refractory anemia with excess of blasts are presented. Trisomy 13 was present as the sole numerical aberration in all analyzed bone marrow metaphases; this finding has not been reported previously in myelodysblastic syndrome.
Asunto(s)
Anemia Refractaria con Exceso de Blastos/genética , Cromosomas Humanos Par 13 , Trisomía , Anciano , Humanos , MasculinoRESUMEN
Hairy cell leukemia (HCL), a rare B-cell chronic lymphoproliferative disorder, is often accompanied by immune abnormalities. A marked impairment of the natural killer cell-mediated cytotoxicity (NK activity) has been reported in most patients at diagnosis. In the present report a long-term follow-up study of NK activity of splenectomized HCL patients is recorded. Among patients who persisted with stable disease two groups, one with normal NK activity, and another with low NK activity, could be recognized. Patients with progressive stage were characterized by a low NK cytotoxic activity. In vitro tests showed that interferon alpha (IFN-alpha) and interleukin 2 (IL2) could increase the NK activity to normal levels only in HCL patients with stable disease, while in progressive HCL these cytokines showed a significantly decreased effect. These results indicate that cytokine-induced NK cytotoxicity appears to be a valuable parameter in assessing the stage of HCL.
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Biomarcadores de Tumor , Interferón Tipo I/farmacología , Interleucina-2/farmacología , Células Asesinas Naturales/efectos de los fármacos , Leucemia de Células Pilosas/patología , Adulto , Anciano , Células Cultivadas , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Leucemia de Células Pilosas/inmunología , Leucemia de Células Pilosas/cirugía , Leucemia de Células Pilosas/terapia , Leucocitos Mononucleares/efectos de los fármacos , Persona de Mediana Edad , Periodo Posoperatorio , Proteínas Recombinantes/farmacología , EsplenectomíaRESUMEN
The investigations were undertaken to evaluate morphometrically the satellite cells (SC) of two muscles: the slow, musclus latissimus dorsi and the fast, musculus gastrocnemius from rats kept in hypokinetic conditions for seven days. The changes in both muscle were of similar character, they concerned a decrease in the Golgi apparatus, rough endoplasmic reticulum fractions and the number of ribosomes, and an increase in the relative volume of heterochromatin content. These findings seem to indicate a reduced activity of the SC. Differences were also demonstrated between the satellite cells in both examined muscles in the control group. They also suggest that the SC are not a homogeneous population as regards parameters evaluated in the present study.
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Músculo Esquelético/fisiología , Músculo Esquelético/ultraestructura , Animales , Hipocinesia , Inmovilización , Masculino , Músculo Esquelético/citología , Orgánulos/fisiología , Orgánulos/ultraestructura , Ratas , Ratas WistarRESUMEN
Ultrastructural morphometric analysis of satellite cells of the diaphragm from one and 30-day-old rats was performed. The nuclear and cytoplasmic components of the cells were evaluated. The results obtained indicate that the satellite cells of one-day-old female rats are in a state of low activity. In 30-day-old animals, on the contrary, the cells are excited and active. This may be connected with their intensive participation in the process of development of the diaphragm muscle.
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Diafragma/crecimiento & desarrollo , Desarrollo de Músculos , Animales , Animales Recién Nacidos , Diafragma/ultraestructura , Femenino , Ratas , Ratas WistarRESUMEN
The analysis was based on 31 patients with chronic granulocytic leukaemia (CGL) treated during the period 1975-1986 and the correlation between the total dose of busulphan administered during the first year of treatment and the duration of chronic phase of the disease was investigated. We found such correlation and also we found that the duration of the chronic phase was more significantly correlated with one year maintenance dose of busulphan. This suggests that the prognosis in CGL is more connected with the proliferation activity of leukaemic cells than with the extent of disease at the time of diagnosis.
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Busulfano/administración & dosificación , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoAsunto(s)
Espermatogonias/ultraestructura , Testículo/citología , Testículo/embriología , Animales , Femenino , Fase G1/fisiología , Masculino , Ratones , Ratones Endogámicos , EmbarazoAsunto(s)
Bacterias/aislamiento & purificación , Cloro , Microbiología de Alimentos , Carne , Pavos , Animales , Clostridium perfringens/aislamiento & purificación , Escherichia coli/aislamiento & purificación , Industria de Procesamiento de Alimentos , Óxidos , Salmonella/aislamiento & purificación , Saneamiento , Microbiología del AguaAsunto(s)
Hernia Diafragmática/patología , Hernia Hiatal/patología , Anciano , Duodeno/patología , Humanos , Masculino , Estómago/patologíaRESUMEN
Purine nucleoside analogues, cladribine (2-chlorodeoxyadenosine, 2-CdA) and fludarabine (FAMP) are active agents in acute myeloid leukemias (AMLs). Synergistic interaction between FAMP or 2-CdA with cytarabine (cytosine arabinoside, Ara-C) has been demonstrated in preclinical and clinical studies. The current multicenter phase II study was initiated to evaluate the efficacy and toxicity of induction treatment consisting of 2-CdA (5 mg/m2), Ara-C (2 g/m2), mitoxantrone (MIT, 10 mg/m2) and granulocyte colony-stimulating factor (G-CSF) (CLAG-M) in refractory AML. In case of partial remission, a second CLAG-M was administered. Patients in complete remission (CR) received consolidation courses based on high-dose Ara-C and MIT with or without 2-CdA. Forty-three patients from five centers were registered: 25 primary resistant and 18 relapsed. CR was achieved in 21 (49%) patients, 20 (47%) were refractory and 2 (5%) died early. Hematologic toxicity was the most prominent toxicity of this regimen. The overall survival (OS; 1 year) for the 42 patients as a whole and the 20 patients in CR were 43% and 73%, respectively. Disease-free survival (1 year) was 68.6%. None of the analyzed prognostic factors influenced the CR and OS probability significantly. We conclude that CLAG-M regimen has significant antileukemia activity in refractory AML, which seems to be better than the activity of many other regimens. The toxicity of the treatment is acceptable.