RESUMEN
High costs of molecule-targeted drugs, such as rituximab, ibritumomab, and tositumomab have given rise to an economical issue for treating patients with non-Hodgkin's lymphoma (NHL). Granulocyte colony-stimulating factors (G-CSFs), which are also expensive, are widely used for treating neutropenia after chemotherapy. In Japan, lenograstim at 2 microg/kg (about 100 microg/body) or filgrastim at 50 microg/m(2) (about 75 microg/body) is commonly administered for patients with NHL after chemotherapy. Therefore, cost-effectiveness is an important issue in treatment for NHL. Patients with advanced-stage NHL who needed chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or a CHOP-like regimen with or without rituximab were enrolled in this randomized cross-over trial to investigate the efficacy and safety of low-dose G-CSF. Half of the patients were administered 75 microg filgrastim in the first course after neutropenia and 50 microg lenograstim in the second course, and the other half were crossed over. Forty-seven patients were enrolled in this cross-over trial, and 24 patients completed the trial. Frequencies and durations of grade 4 leukocytopenia and neutropenia were similar in the two groups. Severe infection was rare and was observed at similar frequency. Frequencies of antibiotics use were also similar. The total cost of G-CSF (cost/drug x duration of administration) was significantly lower in patients who received 50 microg lenograstim. Hence, a low dose of lenograstim might be safe, effective and pharmaco-economically beneficial in patients with advanced-stage NHL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Factor Estimulante de Colonias de Granulocitos/economía , Linfoma no Hodgkin/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Análisis Costo-Beneficio , Estudios Cruzados , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Lenograstim , Linfoma no Hodgkin/economía , Masculino , Persona de Mediana Edad , Neutropenia/tratamiento farmacológico , Neutropenia/etiología , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/economíaRESUMEN
We studied the effect of thrombopoietin (TPO) on interleukin-3 (IL-3)-dependent bone marrow cell colony formation of mice to clarify the role of protein kinase C (PKC) in the signal transduction of TPO for the proliferation of primitive hematopoietic progenitors. TPO alone hardly yielded colonies. However, TPO in combination with IL-3 increased colony numbers synergistically from 2- to 4-fold, compared with those supported by IL-3 alone. Serial observation of colony development showed that TPO may hasten the appearance of colonies by shortening the dormant period (G(0)) of primitive progenitors. Immunocytochemical studies on PKC isoforms in progenitor cells stimulated with TPO have revealed that the expression pattern of PKC-epsilon is changed, but not that of PKC-alpha, -beta, -gamma, -delta, or -zeta. Selective PKC inhibitors, such as calphostin C and GF 109203X, and PKC-epsilon-specific translocation inhibitor peptide abrogated the enhancing effect of TPO on IL-3-dependent colony formation and the changes in the intracellular expression pattern of PKC-epsilon. These data taken together suggest that TPO has a direct effect on primitive progenitors and enhances IL-3-dependent colony formation, at least partly through the activation of PKC-epsilon.
Asunto(s)
Células Madre Hematopoyéticas/metabolismo , Interleucina-3/metabolismo , Isoenzimas/metabolismo , Proteína Quinasa C/metabolismo , Transducción de Señal/fisiología , Trombopoyetina/metabolismo , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Recuento de Células , División Celular/efectos de los fármacos , Células Cultivadas , Células Clonales , Ensayo de Unidades Formadoras de Colonias , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Fluorouracilo/farmacología , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/efectos de los fármacos , Inmunohistoquímica , Interleucina-3/farmacología , Isoenzimas/antagonistas & inhibidores , Masculino , Ratones , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C-epsilon , Transducción de Señal/efectos de los fármacos , Trombopoyetina/farmacologíaRESUMEN
Protein kinase C (PKC) was first described as a calcium-activated, phospholipid-dependent serine/threonine protein kinase 22 years ago, and it has since been studied extensively as a second messenger transducing diverse signals regarding cell proliferation, activation of cellular function, differentiation, and even apoptosis. Because PKC consists of at least 11 isoforms, with possibly different biological properties, it is necessary to reevaluate its known functions as functions of each isoform. Recent studies have revealed that several other lipid metabolites generated by signal-induced hydrolysis of membrane phospholipids, such as ceramide and phosphatidylinositol-3,4,5-triphosphate, may also have the potential to mediate external signals. Here we describe the roles of PKC isoforms in cell proliferation and apoptosis, particularly in relation to other lipid metabolites.
Asunto(s)
Apoptosis/efectos de los fármacos , División Celular/efectos de los fármacos , Proteína Quinasa C/fisiología , Humanos , Isoenzimas/química , Isoenzimas/farmacología , Isoenzimas/fisiología , Proteína Quinasa C/química , Proteína Quinasa C/farmacología , Transducción de SeñalRESUMEN
The numb chin syndrome (NCS) is characterized by chin or lower lip numbness restricted to the distribution of the mental nerve (the distal trigeminal nerve). A case of multiple myeloma with polycythemia vera was diagnosed with NCS as the initial manifestation. A 73-year-old Japanese male was admitted to our hospital in April, 1993, because of paresthesia around the chin and lower lip. X-ray film showed multiple osteolytic lesions. According to serum and urine immunoelectrophoresis, lambda type Bence Jones protein was demonstrated. The bone marrow aspiration showed the normocellular marrow with 14.1% myeloma cells. He was diagnosed a suffering from multiple myeloma and was treated with melphalan and prednisolone. He is alive at present with resolution of NCS. We discussed pathogenesis, diagnosis, and treatment of NCS.
Asunto(s)
Mentón/inervación , Mieloma Múltiple/complicaciones , Sensación , Nervio Trigémino , Anciano , Enfermedades de los Nervios Craneales/etiología , Humanos , Masculino , Mieloma Múltiple/tratamiento farmacológico , Parestesia/etiología , SíndromeRESUMEN
A series of 305 infants and children between 1 day to 14 years of age were operated upon using caudal anesthesia. We used 1% mepivacaine 1.2 ml.kg-1 to obtain a level of anesthesia above T10, 1.0 ml.kg-1 above L1, and 0.8 ml.kg-1 above S. Complete failure occurred in 4.3% of patients. We investigated the blood concentration of mepivacaine in 17 patients, and it ranged from 0.5 microgram.ml-1 to 5.0 micrograms.ml-1. In a two month old infant, weighing 6.7 kg, apnea and bradycardia occurred. This was managed by tracheal intubation and controlled ventilation. But there were no other severe complications. We also investigated the distance between C7 and sacral hiatus (D) in each case. The coefficients of correlation between D and height is 0.97, and high correlation existed also between D and body weight (r = 0.93). This confirms that body weight can be used as a parameter to determine the dose of local anesthetic agent. We conclude that this technique is a safe, reliable and simple way to produce surgical analgesia in infants and children.