RESUMO
OBJECTIVE: A3 adenosine receptor (A3AR) is overexpressed in the skin and peripheral blood mononuclear cells of psoriasis patients. We investigated the efficacy/safety of piclidenoson (CF101), an orally bioavailable A3AR agonist that inhibits IL-17 and IL-23 production in keratinocytes, in moderate-to-severe plaque psoriasis. METHODS: The randomized, placebo- and active-controlled, double-blind phase 3 COMFORT-1 trial randomized patients (3:3:3:2) to piclidenoson 2 mg BID, piclidenoson 3 mg BID, apremilast 30 mg BID or placebo. At Week 16, patients in the placebo arm were re-randomized (1:1:1) to piclidenoson 2 mg BID, piclidenoson 3 mg BID or apremilast 30 mg BID. The primary end point was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI-75) at Week 16 versus placebo. RESULTS: A total of 529 patients were randomized and received ≥1 dose of study medication (safety population). The efficacy analysis population for the primary end point included 426 patients (piclidenoson 2 mg BID, 127; piclidenoson 3 mg BID, 103; apremilast, 118; placebo, 78). Piclidenoson at 2 and 3 mg BID exhibited similar efficacy. The primary end point was met with the 3 mg BID dose: PASI 75 rate of 9.7% versus 2.6% for piclidenoson versus placebo, p = 0.037. The PASI responses with piclidenoson continued to increase throughout the study period in a linear manner. At week 32, analysis in the per-protocol population showed that a greater proportion of patients in the piclidenoson 3 mg BID arm (51/88, 58.0%) achieved improvement from baseline in Psoriasis Disability Index (PDI) compared to apremilast (59/108, 55.1%), and the test for noninferiority trended towards significance (p = 0.072). The safety/tolerability profile of piclidenoson was excellent and superior to apremilast. CONCLUSIONS: Piclidenoson demonstrated efficacy responses that increased over time alongside a favourable safety profile. These findings support its continued clinical development as a psoriasis treatment (ClinicalTrials.gov identifier: NCT03168256).
Assuntos
Psoríase , Talidomida , Humanos , Psoríase/tratamento farmacológico , Masculino , Método Duplo-Cego , Feminino , Pessoa de Meia-Idade , Adulto , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Talidomida/efeitos adversos , Talidomida/administração & dosagem , Índice de Gravidade de Doença , Adenosina/análogos & derivadosRESUMO
Adenomatous polyps are neoplasms that may progress to colorectal cancer. The role of diet and other lifestyle habits in their etiology is now being elucidated. The aim of this study was to evaluate effects of nutritional habits, weight and weight gain, tobacco smoking, and physical activity in adenoma etiology. A quantified dietary history questionnaire was designed to evaluate long-term dietary habits in addition to more recent ones. The study population comprised 196 adenoma patients and matched asymptomatic, screened controls. Statistical analysis used multivariate conditional logistic models, adjusting for total energy intake and physical activity. Odds ratios (ORs) and 95% confidence intervals (CIs) for adenoma associated with highest versus lowest tertiles of mean daily intake were as follows: for energy, OR 3.7 and CI 2.1-6.7; for animal fat, OR 2.4 and CI 1.2-4.7; for tobacco smoking, OR 3.1 and CI 1.1-2.8; and for weight gain, OR 2.2 and CI 1.2-4.1 (P for linear trend for all, < or = 0.01). Significant negative associations were found with intake of total carbohydrates (OR, 0.3; CI, 0.1-0.7) and fluids (OR, 0.4; CI, 0.2-0.8) (P for both < 0.01) as well as for physical activity (OR, 0.6; CI, 0.3-0.9; P = 0.03). Increased risk for adenoma was observed with decreased intake of carotene (OR, 0.6; CI, 0.3-1.0; P = 0.06), vitamin E (OR, 0.6; CI, 0.3-1.0; P = 0.07), and dietary fiber (OR, 0.6; CI, 0.3-1.3; not significant). The OR of interaction between water and dietary fiber was significant (OR, 0.7; CI, 0.6-0.9; P = 0.01), suggesting a synergistic protective effect. Specific dietary and lifestyle habits were identified as independent factors associated with colorectal adenomas; of special interest is the interaction between water and fiber intake. Avoiding these factors might delay or prevent neoplasia.
Assuntos
Adenoma/epidemiologia , Neoplasias Colorretais/epidemiologia , Estilo de Vida , Fenômenos Fisiológicos da Nutrição , Adenoma/etiologia , Adulto , Idoso , Neoplasias Colorretais/etiologia , Fibras na Dieta , Exercício Físico , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Fumar , Inquéritos e Questionários , Água , Aumento de PesoRESUMO
We describe a patient with T-cell prolymphocytic leukemia who developed a large-cell lymphoma of the T-cell type. The neoplastic cells of the large-cell lymphoma demonstrated the same immunologic phenotype (ER+, Leu-3+, Leu-2-, and HLA ABC+) as the cells of the prolymphocytic leukemia, which indicated a clonal evolution of a T-cell prolymphocytic leukemia into a large-cell lymphoma of the T-cell phenotype.
Assuntos
Leucemia Linfoide/patologia , Linfoma/patologia , Idoso , Anticorpos Monoclonais , Humanos , Leucemia Linfoide/imunologia , Linfonodos/patologia , Linfoma/imunologia , Masculino , Fenótipo , Formação de Roseta , Linfócitos T/imunologia , Linfócitos T/patologiaAssuntos
Hemodinâmica , Modelos Biológicos , Estresse Mecânico , Pressão Sanguínea , Vasos Sanguíneos , ElasticidadeAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Leucemia/tratamento farmacológico , Adolescente , Adulto , Agranulocitose/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Infecções/etiologia , Pessoa de Meia-IdadeRESUMO
We investigated the hypoxemia associated with extreme leukocytosis in leukemic patients. In vitro experiments showed that the rate of decrease in the partial pressure of oxygen in the blood samples from such patients was proportional to the white cell count. In the presence of normal white cell count no drop in PO2 was observed. We conclude that a low arterial oxygen tension in the presence of extreme leukocytosis reflects oxygen consumption by leukocytes rather than true hypoxemia. Both normal as well as leukemic leukocytes appear to exhibit this phenomenon.
Assuntos
Hipóxia/complicações , Leucócitos/metabolismo , Leucocitose/complicações , Consumo de Oxigênio , Gasometria , Granulócitos/metabolismo , Humanos , Contagem de Leucócitos , Leucocitose/tratamento farmacológico , Linfócitos/metabolismo , Oxigênio/sangueRESUMO
BACKGROUND: Calcium supplements to the western-style diet may reduce the risk for colorectal neoplasia. Using rectal epithelial proliferation (REP) measurements as a biomarker of response to intervention, the authors evaluated the effects of 1-year calcium supplementation in adenoma patients and its possible interactions with the patients' dietary and lifestyle habits. METHODS: Consenting adenoma patients, without a family history of colorectal neoplasia, were randomly selected to receive 3.75 g calcium carbonate (1.5 g Ca2+) daily or to receive no treatment. All had their long-term dietary and lifestyle habits assessed and their REP labeling index (LI) evaluated before and at end of follow-up. The change in LI was compared between groups, and statistical associations were examined between mean nutrient consumption and treatment effect and between lifestyle and treatment effect. RESULTS: Fifty-two adenoma patients (33 treated and 19 untreated) completed intervention and follow-up. There were no significant differences between study groups in age, weight, cigarette smoking, or medication use. The LI decreased in 58% of calcium-intervened patients and in only 26% of nonintervened patients (P = 0.04); the mean LI x 100 (+/- standard deviation) of the former fell from 5.04 +/- 1.93 to 4.54 +/- 1.58, and rose from 4.32 +/- 1.58 to 4.93 +/- 1.58 in the latter (P = 0.04). A lower fat, a higher carbohydrate, fiber, or fluid intake each interacted with the calcium supplementation to decrease the LI (P = 0.02, 0.001, 0.02, and 0.08, respectively). CONCLUSIONS: Long-term calcium supplements significantly suppressed REP in adenoma patients, and long-term dietary habits contributed to this effect. Patient diet should be assessed when researchers use REP as a biomarker in calcium chemoprevention studies. Study results indicated that relevant dietary counseling may be useful in addition to calcium supplements in persons at increased risk for colorectal neoplasia.
Assuntos
Adenoma/prevenção & controle , Carbonato de Cálcio/uso terapêutico , Neoplasias Colorretais/prevenção & controle , Células Epiteliais/efeitos dos fármacos , Adenoma/patologia , Adulto , Idoso , Biópsia , Divisão Celular/efeitos dos fármacos , Quimioprevenção , Neoplasias Colorretais/patologia , Dieta , Suplementos Nutricionais , Feminino , Humanos , Imuno-Histoquímica , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Reto/patologiaRESUMO
BACKGROUND: The effect of environmental factors has been demonstrated in the pathogenesis of inflammatory bowel disease (IBD). Nutrition may be one of them. AIM: To investigate the pre-illness diet in patients with recent IBD in comparison with matched population and clinic controls. METHODS: Quantified dietary histories were obtained from 87 patients with recent IBD (54 ulcerative colitis (UC) and 33 Crohn's disease (CD)) and 144 controls. Odds ratios (OR) for IBD were derived for intake levels of various foods. RESULTS: A high sucrose consumption was associated with an increased risk for IBD (OR 2.85 (p = 0.03) against population controls and 5.3 (p = 0.00) against clinic controls). Lactose consumption showed no effect while fructose intake was negatively associated with risk for IBD (NS). Similar trends were noted in UC and CD. A high fat intake was associated with an increased risk for UC; this was particularly marked for animal fat (OR 4.09, p = 0.02) and cholesterol (OR 4.57, p = 0.02). A high intake of fluids (p = 0.04), magnesium (p = 0.04), vitamin C, and fruits (NS) was negatively associated with the risk for IBD, while a positive association was found for retinol (p = 0.01). Most of the findings were similar in UC and CD except for potassium and vegetable consumption which showed a negative association only with risk for CD. CONCLUSIONS: An association was found between pre-illness diet and subsequent development of UC and CD. The effect of dietary components may be primary or modulatory.
Assuntos
Dieta , Doenças Inflamatórias Intestinais/etiologia , Adulto , Estudos de Casos e Controles , Colite Ulcerativa/etiologia , Doença de Crohn/etiologia , Dieta/efeitos adversos , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Feminino , Humanos , Masculino , Micronutrientes , Fatores de RiscoRESUMO
Our aim was to evaluate the role of maternal nutritional habits during the period of gestation and of children subsequent diet in the etiology of pediatric brain tumors. All cases of incident nervous system tumors under age 18, diagnosed between 1984 and 1993 (n = 300) in Israel were identified. Two matched population controls per case were selected (n = 574). Personal interviews, using a semi-quantified three-step food frequency questionnaire, were performed. Univariate analysis showed that increased child consumption of vegetable fat [p trend 0.01; 95% confidence interval (CI) 1.1-3.2], carbohydrates (p trend 0.05; CI 1.0-5.9), and vitamin E (p trend 0.05; CI 1.0-3.3), were significantly associated with brain tumor risk. No associations were found with nitrate, nitrite or vitamin C. A significant positive association with potassium consumption (p trend 0.01; CI 1.1-3.7) was noted during gestation. Results of multivariate analysis showed that the only persisting associations were with vegetable fat (OR = 1.36; CI 1.06-1.73) in the child diet and potassium intake during gestation (OR = 1.44; CI 1.04-1.99). In conclusion, nutritional associations with pediatric brain tumor etiology, remain unsubstantiated.
Assuntos
Neoplasias Encefálicas/etiologia , Dieta , Comportamento Materno , Estado Nutricional , Adolescente , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Ingestão de Alimentos , Feminino , Humanos , Lactente , Masculino , Análise Multivariada , GravidezRESUMO
A review of 162 patients with Hodgkin disease disclosed 36 with microcytic anemia (mean corpuscular hemoglobin values [MCV] less than 80 fl). Three patients had iron deficiency, and one had beta-thalassemia. Of the remaining 32 patients, 24 had microcytic anemia at the time of diagnosis of Hodgkin disease, and ten, including two patients with this finding initially, developed microcytic anemia in association with recurrence of Hodgkin disease. Seven patients with Hodgkin disease and normal MCV had normal alpha-to-beta-globin chain ratios (1.0 +/- 0.14). Seven patients with Hodgkin disease and MCV less than 80 fl had significantly lower alpha-to-beta chain ratios (0.66 +/- 0.05). Twelve normal controls and four with iron-deficiency anemia and MCV less than 80 fl had normal ratios. Anemia was corrected, and MCV returned to normal in all patients who responded to therapy for Hodgkin disease. In the two patients studied sequentially, abnormal alpha-to-beta-chain ratio was corrected along with the anemia.
Assuntos
Anemia/sangue , Globinas/biossíntese , Doença de Hodgkin/sangue , Anemia/etiologia , Volume de Eritrócitos , Eritrócitos/citologia , Doença de Hodgkin/complicações , Doença de Hodgkin/patologia , Humanos , Estadiamento de NeoplasiasRESUMO
We designed a treatment program to improve the outcome for adults with acute lymphoblastic leukemia (ALL). Treatment included a remission-induction phase followed by intensive alternating cycles of non-cross-resistant chemotherapy and prolonged oral maintenance therapy. Eighty-one consecutive previously untreated patients were entered on this study. Ninety-four percent of patients entered complete remission. A Kaplan-Meier analysis predicts that 53% +/- 9% (SEM) of patients in remission will remain free of disease at 3 years. Neither age, sex, WBC count, nor immunophenotype had a significant effect on remission duration. This program of intensive cyclical chemotherapy has improved the disease-free survival of patients with adult ALL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia Linfoide/tratamento farmacológico , Adolescente , Adulto , Feminino , Humanos , Leucemia Linfoide/imunologia , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
Bone marrow transplantation has become the treatment of choice for patients with severe aplastic anemia who are fortunate enough to have allogeneic sibling donors. As patients have been transplanted earlier in the course of their disease, significant improvements have been obtained in long-term survival. However, in patients who have been sensitized by previous blood product transfusions, graft rejection continues to be a significant problem and second transplants when performed are frequently unsuccessful. This case report deals with a patient with myositis ossificans progressiva (MOP) who developed severe idiopathic aplastic anemia. He rejected his first graft after 160 days. However, he was successfully reingrafted with marrow from the same donor using a different conditioning regimen.
Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea , Miosite Ossificante/complicações , Soro Antilinfocitário/uso terapêutico , Criança , Doença Enxerto-Hospedeiro , Humanos , Contagem de Leucócitos , MasculinoRESUMO
A phase II trial of cytarabine, cisplatin, and etoposide was conducted in 38 patients with refractory stage III and IV non-Hodgkin's lymphoma. There were two complete and nine partial responses (32%) among 35 evaluable patients. Response rate in patients with large cell lymphoma was 45%. The dose-limiting toxic effect was myelosuppression in 66% of patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Citarabina/administração & dosagem , Avaliação de Medicamentos , Etoposídeo/administração & dosagem , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Linfoma não Hodgkin/patologia , MasculinoRESUMO
Of 33 patients who had undergone allogeneic bone marrow transplantation during first complete remission of acute nonlymphocytic leukemia, 21 patients have now been followed in continued complete remission for 6-64 mo (median greater than 18 mo) without maintenance chemotherapy. The median age of the surviving patients is 27 yr. Transplant-related complications occurring throughout the first year after marrow grafting were fatal in 7 patients, and leukemic recurrence led to the death of 5 patients. The actuarial long-term disease-free survival is 60% and the actuarial remission rate is 79%.
Assuntos
Transplante de Medula Óssea , Leucemia/terapia , Medula Óssea/efeitos dos fármacos , Medula Óssea/efeitos da radiação , Ciclofosfamida/uso terapêutico , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Humanos , Leucemia/tratamento farmacológico , Leucemia/mortalidade , Leucemia/radioterapia , Isolamento de Pacientes , Irradiação Corporal TotalRESUMO
A 28-yr-old woman with acute malignant myelosclerosis received, as primary treatment, ablative chemotherapy and total body radiation therapy followed by bone marrow transplantation from her histocompatible brother. The patient is now well more than 15 mo after bone marrow transplantation, with normal peripheral blood counts, a normal bone marrow, no evidence of graft-versus-host disease, and is on no therapy. In light of the poor results obtained with conventional chemotherapy in this disease, bone marrow transplantation may represent the treatment of choice for patients who have an appropriate donor.
Assuntos
Transplante de Medula Óssea , Mielofibrose Primária/terapia , Doença Aguda , Adulto , Feminino , HumanosRESUMO
A right atrial catheter has proven to be a well-tolerated technical advance for patients requiring prolonged vascular access. It is easily inserted and suited for ambulatory maintenance by the patient. Catheters are utilized for a wide spectrum of iv medications with an acceptably low complication rate. Most significantly, the infection rate is negligible, despite severely compromised hosts. Their use should be considered for any patient in whom problems with vascular access are anticipated. This report comprises our experience with the first 70 catheters in 66 patients in the Hematology/Oncology service.
Assuntos
Cateterismo Cardíaco , Cateteres de Demora , Neoplasias/terapia , Assistência Ambulatorial , Cateterismo Cardíaco/instrumentação , Cateterismo/métodos , Cateteres de Demora/efeitos adversos , Átrios do Coração , Doença de Hodgkin/terapia , Humanos , Infusões Parenterais , Leucemia/terapia , Fatores de TempoRESUMO
Infiltration of extrahemopoietic tissue with leukemic cells was evaluated as a prognostic indicator in 18 patients with acute leukemia undergoing bone marrow transplantation. When compared to 107 patients who did not have extramedullary leukemia at any time prior to marrow grafting, the patients with leukemic invasion into organs outside the hemopoietic system had a significant increase of leukemic recurrence and a significant decrease in survival after marrow transplantation. Extramedullary leukemia may be a negative prognostic indicator for bone marrow transplantation candidates.
Assuntos
Transplante de Medula Óssea , Leucemia/terapia , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , HumanosRESUMO
Thirty-three patients with acute leukemia (15 with lymphoblastic leukemia and 18 with myeloblastic leukemia) were entered into a program of high-dose radiochemotherapy followed by allogeneic bone-marrow transplantation. These patients were in various clinical stages of disease. Of 10 in complete hematologic remission at the time of transplantation, seven were alive without maintenance therapy at the time of evaluation, eight to 35 months after grafting; one was in relapse. Of 11 who received transplants during partial remission, six were in remission without further treatment eight to 33 months after transplantation. In 12 the disease was refractory to chemotherapy when preparation for transplantation was started, and only one of them was alive and free of disease after 10 months. Recurrent leukemia, graft-versus-host disease, viral pneumonia, and early therapy-related toxicity were the major causes of failure. High-dose chemotherapy and total-body irradiation followed by allogeneic marrow transplantation performed during complete or partial remission can produce long-term remission of acute leukemia.