RESUMO
The immunomodulator AS101 has previously been found to induce mouse and human hematopoietic cells to secrete cytokines such as interleukin-1 alpha (IL-1 alpha), IL-2, tumor necrosis factor-alpha (TNF-alpha), and gamma interferon (IFN-gamma). The compound was shown to protect mice from lethal and sublethal effects of chemotherapy and irradiation. AS101 prevented the decrease in the number of bone marrow (BM) and spleen myeloid progenitor cells, and increased the survival of lethally treated mice. In this study, we show a dose-dependent response of AS101 in the induction of high secretion levels of IL-6, IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and stem cell factor (SCF). Since these growth factors are known to induce the proliferation and differentiation of multilineage progenitors, including megakaryocytic and erythroid progenitors, we designed this study to evaluate the role of AS101 in attenuating thrombocytopenia, anemia, and multilineage myelosuppression associated with chemotherapy. We demonstrate that pretreatment of mice with AS101 24 hours before intraperitoneal injection of 250 mg/kg cyclophosphamide (CYP) or intravenous injection of 150 mg/kg 5-fluorouracil (5-FU) significantly increased the number of circulating white blood cells (WBC) and platelets. The numbers of both neutrophils and lymphocytes were significantly increased in AS101-treated mice subjected to chemotherapy. In addition, AS101 attenuated erythropenia caused by 5-FU. It could also increase megakaryocyte and erythroid progenitor cells (CFU-MK and CFU-E) in the BM of treated mice severely affected by chemotherapy. We demonstrate that the protective effect of AS101 could be abrogated by treatment with anti-IL-1R or anti-SCF antibodies. We suggest that the endogenous production of cytokines such as IL-1, IL-6, IL-3, SCF, and GM-CSF in mice treated with AS101 offers protection to circulating blood elements and ameliorates the reconstitution of megakaryocytic and erythroid progenitors. The simultaneous protection by AS101 of multilineage cell compartments is probably due to stimulation by AS101 of a selective subpopulation of primitive stem cells resistant to chemotherapy. On the basis of these studies, phase II clinical trials with patients treated with chemotherapy in combination with AS101 have been initiated.
Assuntos
Adjuvantes Imunológicos/farmacologia , Antineoplásicos/toxicidade , Doenças da Medula Óssea/prevenção & controle , Etilenos/farmacologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Anemia/induzido quimicamente , Anemia/prevenção & controle , Animais , Doenças da Medula Óssea/induzido quimicamente , Células Cultivadas , Ciclofosfamida/toxicidade , Fluoruracila/toxicidade , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Interleucina-3/metabolismo , Interleucina-6/metabolismo , Masculino , Megacariócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Fator de Células-Tronco/metabolismo , Trombocitopenia/induzido quimicamente , Trombocitopenia/prevenção & controleRESUMO
An experimental double-blind study to evaluate the effectiveness of a constant current stimulator was performed on 30 young pigs that underwent a spinal fusion at the level of L5-L6. The group of animals with an active bone-growth stimulator showed a statistically significant increase of osteoblastic activity with bone formation.
Assuntos
Desenvolvimento Ósseo , Terapia por Estimulação Elétrica , Fusão Vertebral , Animais , Método Duplo-Cego , Vértebras Lombares/fisiologia , Vértebras Lombares/cirurgia , Suínos , CicatrizaçãoRESUMO
A case of synovial osteochondromatosis in a synovial recess of the shoulder joint, which is considered to be a very rare condition, is presented. Different clinical and pathologic aspects of this condition are reviewed and discussed. Treatment consists of a surgical removal of the free loose osteocartilaginous bodies with a partial excision of the affected synovia. The condition did not recur.
Assuntos
Condroma , Articulação do Ombro , Membrana Sinovial , Adulto , Condroma/patologia , Condroma/cirurgia , Humanos , Masculino , Articulação do Ombro/patologia , Sinovectomia , Membrana Sinovial/patologiaRESUMO
A useful method for the diagnosis of acute rupture of the lateral ligament of the ankle joint is presented. Twenty-three patients with ruptures of the lateral ligament of the ankle joint were treated surgically with suture of the lateral ligaments of the ankle. Accurate preoperative diagnosis with stress films and arthrography under local anesthesia of the ankle joint is imperative. No instances of infection or other complications were observed. All patients achieved a normal range of ankle function within three to six months. Radiograhs of the injured ankle in the forced inversion position following operation showed full stability of the ankle joint. In our opinion, all ankle injuries should be examined roentgenographically with forced inversion of the foot. Tilting of the talus of at least 10 degrees must be followed by arthrography of the ankle joint under local anesthesia. If there is leakage of contrast material along the peroneal tendon sheaths and around the joint cavity, the lateral ligament of the ankle must be sutured immediately in order to regain stability of the ankle joint.
Assuntos
Traumatismos do Tornozelo , Ligamentos Articulares/lesões , Entorses e Distensões/diagnóstico , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Humanos , Ligamentos Articulares/cirurgia , Radiografia , Ruptura , Entorses e Distensões/complicaçõesAssuntos
Cifose/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Complicações Pós-OperatóriasAssuntos
Artérias/lesões , Extremidades/lesões , Procedimentos Cirúrgicos Vasculares , Veias/lesões , Acidentes de Trânsito , Amputação Cirúrgica , Traumatismos por Explosões/cirurgia , Prótese Vascular , Pré-Escolar , Humanos , Masculino , Medicina Militar , Obstrução da Artéria Renal/complicações , Veia Safena/transplante , Trombose/cirurgia , Ferimentos e Lesões/complicações , Ferimentos por Arma de Fogo/cirurgiaAssuntos
Tornozelo , Doenças Ósseas/etiologia , Cartilagem Articular , Joelho , Sarcoma Sinovial/complicações , Adulto , Idoso , Artrodese , Reabsorção Óssea/etiologia , Feminino , Humanos , Masculino , Meniscos Tibiais/patologia , Pessoa de Meia-Idade , Sarcoma Sinovial/patologia , Sarcoma Sinovial/cirurgia , Membrana Sinovial/patologiaAssuntos
Doença da Descompressão/complicações , Osteonecrose/etiologia , Adulto , Fêmur , Humanos , Úmero , MasculinoRESUMO
Closed reduction of an anterior dislocation of the hip joint in a 15-year-old boy failed because of interposition of capsule, iliopsoas and rectus femoris muscles. The immediate complications were compression of the common femoral artery, tear of the femoral vein, and fat embolism 24 hours after the injury. The sequelae were periarticular ossification and avascular necrosis of the femoral head. The definitive treatment was a Charnley total hip arthroplasty.
Assuntos
Embolia Gordurosa/complicações , Artéria Femoral/lesões , Veia Femoral/lesões , Luxação do Quadril/etiologia , Adolescente , Angiografia , Artroplastia , Luxação do Quadril/diagnóstico por imagem , Luxação do Quadril/cirurgia , Humanos , MasculinoRESUMO
Two patients suffering from Paget's disease, involving the hip joint, with pain and limitation of movement, were treated by total hip replacement. The operative course was normal and without excessive bleeding. At follow-up five years later, the patients are free of pain, and have almost complete range of motion; there is no sign of prosthetic loosening.