RESUMEN
OBJECTIVE: The Stroke Angel initiative investigates the implementation of telemedicine for improvement of preclinical communication between emergency medical services (EMS) and stroke units in cases of acute stroke. MATERIAL AND METHODS: Stroke Angel is a technical system for the telemedical prenotification of patients in cases of suspected stroke at a stroke unit by the EMS. Within the framework of an observational study, the team has been investigating the effects of the system on door-to-computed tomography (CT) and door-to-needle times as well as the lysis rate in the neighboring regions of Rhön-Grabfeld and Bad Kissingen since 2005. RESULTS: The system supports the acute treatment of neurological emergencies and functions as a catalyst for the interlinking of medical institutions in the region as well as for communication between emergency physicians/EMS and hospital physicians. The use of a computer-based data collection enables a continuous improvement process leading to an acceleration of internal clinical procedures and an increase of the lysis rate with the mortality rate staying constant. CONCLUSION: Telemedicine is applicable in the preclinical care of acute stroke and, thanks to the computer-based data collection, leads to an increase in process transparency, which helps to improve the internal clinical processes in and around a stroke unit.
Asunto(s)
Servicios Médicos de Urgencia/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Sistemas de Comunicación en Hospital/estadística & datos numéricos , Accidente Cerebrovascular/terapia , Telemedicina/estadística & datos numéricos , Tiempo de Tratamiento/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Ambulancias/estadística & datos numéricos , Eficiencia Organizacional/estadística & datos numéricos , Femenino , Alemania , Humanos , Persona de Mediana Edad , Telemedicina/métodosRESUMEN
The use of modern information and telecommunication technologies enables telerehabilitation of neurological deficits in the domestic environment. The current state of studies on rehabilitative teletherapy for improvement of motor function and mobility deficits due to stroke is reviewed. Two neurolinguistic proof of concept studies investigating the efficacy of online interactive telespeech therapy are reported, which compared virtual screen to screen interactive telerehabilitation of aphasia after stroke and dysarthrophonia in Parkinson's disease to conventional face to face rehabilitation. The results of the studies indicate that the neurological rehabilitation of motor and communicative deficits in the domestic environment of patients by means of teletherapy is just as efficient as conventional rehabilitation. Under home-based telerehabilitation patient transfer becomes unnecessary. Rehabilitative Teletherapy is a posthospital component of a cross-sector supply chain for patients with handicaps or impairments due to stroke and other neurological diseases.
Asunto(s)
Biorretroalimentación Psicológica/métodos , Consulta Remota/métodos , Autocuidado/métodos , Trastornos del Habla/rehabilitación , Rehabilitación de Accidente Cerebrovascular/métodos , Telerrehabilitación/métodos , Medicina Basada en la Evidencia , Alemania , Servicios de Atención de Salud a Domicilio , Humanos , Terapia Asistida por Computador/métodos , Resultado del Tratamiento , Interfaz Usuario-ComputadorRESUMEN
A female with autism, aged over 40 years, who had been hospitalized in a nursing home, developed descending necrotizing mediastinitis requiring tracheostomy. Subsequently, tracheal stenosis was observed. She was referred to our hospital. T-tube therapy was selected, and there has been no recurrence during the 3-year follow-up. We report a patient in whom a T-tube was useful for treating benign tracheal stenosis in the presence of autism.
Asunto(s)
Trastorno Autístico/complicaciones , Intubación Intratraqueal/instrumentación , Estenosis Traqueal/terapia , Adulto , Femenino , HumanosRESUMEN
Flail chest occurs by blunt chest trauma and is associated with pulmonary contusion, atelectasis, pneumothorax, hemothorax, and respiratory failure. Because of its severity, it may need internal pneumatic stabilization or surgical fixation. Some patients do not need the internal stabilization and are observed conservatively. Some of these patients, however, increase the flail after palliating the pain and getting up. These patients show inefficient ventilation and surgical fixation is needed. The operation should be performed after the improvement of pulmonary contusion. In this paper, we presented 2 patients who showed such course and clarified the surgical methodology.
Asunto(s)
Tórax Paradójico/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Procedimientos Quirúrgicos Torácicos/métodosRESUMEN
To determine the efficacy and toxicity of irinotecan combined with carboplatin, we conducted a phase II trial. Eligibility criteria were: chemotherapy-naïve, small-cell lung cancer (SCLC), good performance status (PS: 0-2), ageAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
, Carcinoma de Células Pequeñas/tratamiento farmacológico
, Neoplasias Pulmonares/tratamiento farmacológico
, Anciano
, Camptotecina/administración & dosificación
, Camptotecina/análogos & derivados
, Carboplatino/administración & dosificación
, Progresión de la Enfermedad
, Femenino
, Humanos
, Irinotecán
, Masculino
, Persona de Mediana Edad
, Análisis de Supervivencia
, Resultado del Tratamiento
RESUMEN
Autoantibodies against heat shock protein 40 (HSP40) and their clinical significance in ulcerative colitis (UC) have not been evaluated before. Twenty-six tissue specimens of inflamed areas from patients with UC, 16 from patients with Crohn's disease (CD) and 16 endoscopically normal tissues were analysed for HSP40 expression. Sera from 47 patients with UC and 44 healthy volunteers were examined for the presence of autoantibodies against HSP40 by enzyme-linked immunosorbent assay test. Immunohistochemistry showed that 17 out of 26 specimens from UC patients, one specimen from a CD patient and one normal tissue specimen were positive for HSP40. Most HSP40-positive cells expressed CD68. Higher titres of anti-HSP40 autoantibodies were detected in sera from UC patients compared with healthy volunteers. In patients with inactive disease, those with proctitis or left-sided colitis had higher titres of anti-HSP40 autoantibodies than those with total colitis. Our study suggests that autoimmunity against HSP40 may have a beneficial effect in UC patients by limiting the extent of the disease.
Asunto(s)
Autoanticuerpos/sangre , Colitis Ulcerosa/inmunología , Proteínas de Choque Térmico/inmunología , Adolescente , Adulto , Anciano , Femenino , Proteínas del Choque Térmico HSP40 , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIM: To observe hemichrome formation in human haemoglobin A under various buffer conditions. METHOD: Hemichrome formation of human oxyhaemoglobin A (HbO2) was studied spectrophotometrically in 0.1 m buffer at various temperatures and pH values. RESULTS: Following autoxidation in ferrous HbO2, it was evident that formation of hemichrome, which tends to precipitate, occurred at various stages during the course of the autoxidation reaction namely at initial, intermediate or final stages, depending on temperature and pH of the solution. By varying temperature of the solution from 35 to 55 degrees C and pH from 4.5 to 10.5, it is shown here that HbO2 exhibits high susceptibility for hemichrome formation and its occurrence is a function of pH, temperature and progress of autoxidation of HbO2. Unlike HbO2 and its separated haemoglobin chains, monomeric bovine heart myoglobin (MbO2) did not easily form hemichrome. CONCLUSION: These findings provide a clue on the crucial role of haemoglobin molecule for senescent cell recognition or homeostasis in the blood circulation.
Asunto(s)
Hemoproteínas/química , Hemoglobina A/química , Oxihemoglobinas/química , Animales , Tampones (Química) , Bovinos , Humanos , Concentración de Iones de Hidrógeno , Mioglobina/química , Oxidación-Reducción , Desnaturalización Proteica , Espectrofotometría , TemperaturaRESUMEN
Interleukin 6 (IL-6) is a pleiotropic cytokine with many physiological functions. The present study was designed to determine the expression of IL-6 and its receptor (IL-6R) in human gastric and colorectal cancers. Nine gastric- and nine colorectal cancer cell lines were analysed. The IL-6 gene was expressed in two gastric cancer cell lines and one colorectal cancer cell line; however, most of the cancer cell lines studied expressed the IL-6R gene. The level of IL-6 secretion in the gastric cancer cell lines correlated with the level of soluble IL-6R secretion, and was significantly higher (< approximately 100 pg/ml) than the level of IL-6 secretion in the colorectal cancer cell lines (< approximately 50 pg/ml). These results suggest that IL-6 may act in a paracrine fashion rather than an autocrine fashion in these cell lines.
Asunto(s)
Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , Interleucina-6/metabolismo , Neoplasias Gástricas/metabolismo , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Humanos , Neoplasias Gástricas/genéticaRESUMEN
We conducted a phase I study of irinotecan (CPT-11) and cisplatin with concurrent split-course radiotherapy in limited-disease small-cell lung cancer (LD-SCLC). This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of this therapy. Four chemotherapy cycles of CPT-11 (days 1, 8 and 15) and cisplatin (day 1) were repeated every 28 days. Radiotherapy of 2 Gy/day commenced on day 2 of each chemotherapy cycle with 20 Gy administered from the first to the third cycles (a total of 60 Gy). 17 patients were enrolled at three dose levels (CPT-11/cisplatin: 40/60, 50/60 and 60/60 mg/m(2)), and 16 were evaluable for toxicity and outcome. 2 of 4 patients at 60/60 mg/m(2) refused continuation of therapy because of general fatigue, and the relative dose intensity of CPT-11 at 50/60 mg/m(2) was approximately 50%. These levels were considered as the MTD. Tumour responses included four complete responses (CR), 11 partial responses (PR) and one no change (NC), and the overall response rate was 93.8% (95% confidence interval: (CI) 71.7-98.9%). This combined modality is tolerable, and CPT-11/cisplatin of 40/60 mg/m(2) in this modality is recommended for phase II study.
Asunto(s)
Camptotecina/análogos & derivados , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Adulto , Anciano , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Terapia Combinada/métodos , Relación Dosis-Respuesta a Droga , Femenino , Enfermedades Hematológicas/inducido químicamente , Humanos , Irinotecán , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
We conducted a phase I study of paclitaxel and irinotecan (CPT-11) in advanced non-small cell lung cancer (NSCLC). This study aimed to determine the maximum tolerated doses (MTD). The pharmacokinetics of CPT-11 and its major active metabolite, SN-38, were also analysed. Patients received paclitaxel (day 1) followed by CPT-11 (days 1, 8 and 15), in a 4-week cycle, and paclitaxel and CPT-11 were escalated from 120 and 40 mg/m(2), respectively. 28 patients were enrolled, who were evaluated for toxicity. 2 of 6 patients at 210 mg/m(2) paclitaxel and 50 mg/m(2) CPT-11, and 2 of 4 at 180 and 60 mg/m(2) developed dose-limiting toxicity (DLT) (neutropenia, fever, neurotoxicity and diarrhoea). The area under the plasma concentration-time curve (AUC) of CPT-11 on day 1 was significantly higher than that on days 8 or 15 at each dose level (P=0.002). The AUC of SN-38 on day 1 was significantly increased using paclitaxel doses >or=150 mg/m(2). A preceding paclitaxel administration changed the pharmacokinetics of CPT-11 and SN-38. However, the toxicity was tolerable. Paclitaxel 180 mg/m(2) and CPT-11 50 mg/m(2) were the recommended doses for further phase II study of this combination.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/farmacocinética , Relación Dosis-Respuesta a Droga , Femenino , Enfermedades Hematológicas/inducido químicamente , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/farmacocinéticaRESUMEN
The aim of the present study was to investigate whether CYP2C19 polymorphism status and gastric emptying are related to healing in patients with gastric ulcers. We studied the CYP2C19 status in seven patients with proton pump inhibitor (PPI)-resistant ulcers, 21 with PPI-sensitive ulcers and 46 healthy volunteers using polymerase chain reaction restriction fragment length polymorphism to detect CYP2C19m1 mutation in exon 5 and CYP2C19m2 mutation in exon 4. Gastric emptying was evaluated using the 13C-acetate breath test. The frequency of phenotypes, indicated by genotypes, did not differ significantly between the three patient groups. The peak time of 13C excretion in patients with PPI-resistant ulcers was significantly longer than that of patients with PPI-sensitive ulcers and healthy volunteers. Our results suggest that rate of gastric emptying, but not CYP2C19 polymorphism, is likely to be an important factor in the delayed healing of patients with PPI-resistant gastric ulcer.
Asunto(s)
Hidrocarburo de Aril Hidroxilasas/genética , Vaciamiento Gástrico/fisiología , Oxigenasas de Función Mixta/genética , Omeprazol/análogos & derivados , Inhibidores de la Bomba de Protones , Úlcera Gástrica/genética , 2-Piridinilmetilsulfinilbencimidazoles , Adulto , Antiulcerosos/uso terapéutico , Hidrocarburo de Aril Hidroxilasas/fisiología , Bencimidazoles/uso terapéutico , Citocromo P-450 CYP2C19 , Femenino , Vaciamiento Gástrico/genética , Humanos , Lansoprazol , Masculino , Persona de Mediana Edad , Oxigenasas de Función Mixta/fisiología , Omeprazol/uso terapéutico , Polimorfismo Genético/fisiología , Rabeprazol , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/enzimología , Úlcera Gástrica/fisiopatologíaRESUMEN
Methylthioadenosine phosphorylase (MTAP) is an important enzyme used for the salvage of adenine and methionine. Cells lacking this enzyme are expected to be sensitive to purine synthesis inhibitors and/or methionine starvation. We reported previously that the MTAP gene is deleted in adult T cell leukemia (ATL) cells. In the present study, we expanded our series and used a real-time quantitative PCR assay for accurate diagnosis of the deletion and nine of 65 primary ATL samples (13.8%) were MTAP negative. In spite of this low incidence, ATL cells showed significantly higher sensitivity to L-alanosine, an inhibitor of de novo adenosine monophosphate (AMP) synthesis, than normal lymphocytes, suggesting that the MTAP gene is inactivated not only by deletion but also by other mechanisms. Indeed, a real-time quantitative RT-PCR assay disclosed that primary ATL cells had significantly lower MTAP mRNA expression than normal lymphocytes. Since MTAP-negative ATL cell lines also showed much higher sensitivity to L-alanosine than MTAP-positive ATL cell lines, we used these cell lines to investigate whether it is possible to develop selective therapy targeting MTAP deficiency. A substrate of MTAP, methylthioadenosine (MTA) or its substitutes rescued concanavalin A (Con A)-activated normal lymphocyte proliferation from L-alanosine toxicity. All the compounds except 5'-deoxyadenosine, however, also caused the undesirable rescue of MTAP-negative ATL cell lines. 5'-Deoxyadenosine had the desired ability to rescue hematopoietic progenitor cells without rescuing ATL cell lines. These results support the rationale for a chemotherapy regimen of L-alanosine combined with 5'-deoxyadenosine rescue in MTAP-deficient ATL.
Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/enzimología , Purina-Nucleósido Fosforilasa/deficiencia , Adenosina Monofosfato/metabolismo , Southern Blotting , División Celular , Ensayo de Unidades Formadoras de Colonias , Cartilla de ADN/química , Resistencia a Antineoplásicos , Eliminación de Gen , Humanos , Leucemia-Linfoma de Células T del Adulto/metabolismo , Activación de Linfocitos , Purina-Nucleósido Fosforilasa/genética , ARN Mensajero/metabolismo , ARN Neoplásico/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Timidina/metabolismoRESUMEN
Overexpression of breast cancer resistance protein (BCRP) ABCG2 reportedly confers cancer cell resistance to camptothecin-based anticancer drugs, such as topotecan and 7-ethyl-10-hydroxycamptothecin (SN-38: the active metabolite of irinotecan). We have recently shown that SN-38-selected PC-6/SN2-5H human lung carcinoma cells overexpressed BCRP with the reduced intracellular accumulation of SN-38 and SN-38-glucuronide (S. Kawabata et al., Biochem. Biophys. Res. Commun. 280, 1216-1223, 2001). In the present study, we have examined whether BCRP transports SN-38 and/or SN-38-glucuronide in vitro, by using plasma membrane vesicles from the parental PC-6 and resistant PC-6/SN2-5H cells, where SN-38 and SN-38-glucuronide accumulation in membrane vesicles was measured by HPLC. Both SN-38 and SN-38-glucuronide were ATP-dependently transported into membrane vesicles prepared from PC-6/SN2-5H cells, whereas no transport activity was observed in membrane vesicles from PC-6 cells. The kinetic parameters of the transport observed in PC-6/SN2-5H vesicles were K(m) = 4.0 microM, V(max) = 714 pmol/mg/min for SN-38 and K(m) = 26 microM, V(max) = 833 pmol/mg/min for SN-38-glucuronide. These findings suggest that BCRP expressed in PC-6/SN2-5H cells transports both SN-38 and SN-38-glucuronide with a higher affinity toward SN-38.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Antineoplásicos Fitogénicos/metabolismo , Camptotecina/análogos & derivados , Camptotecina/metabolismo , Resistencia a Antineoplásicos/fisiología , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/farmacología , Antineoplásicos Fitogénicos/farmacocinética , Transporte Biológico/efectos de los fármacos , Camptotecina/farmacocinética , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Cromatografía Líquida de Alta Presión , Glucurónidos/metabolismo , Humanos , Irinotecán , Cinética , Vesículas Secretoras/efectos de los fármacos , Vesículas Secretoras/metabolismo , Células Tumorales CultivadasRESUMEN
Despite rapid progress in methods for analyzing radiation effects, much remains to be learned about the mechanisms and processes of radiation-induced immunological dysfunction. Among 17,899 sera obtained from atomic bomb survivors in Nagasaki, Japan, sera from 484 participants who complied with a reexamination for alkaline phosphatase (ALP) were tested for antimitochondrial antibody (AMA) by indirect immunofluorescence, and autoantibodies against 2-oxo-acid dehydrogenase complex (2-OADC) by immunoblotting to investigate the prevalence of primary biliary cirrhosis (PBC). Of these 484 sera, 28 (5.8%) were seropositive for AMA. The 484 participants were divided into three groups according to distance from the hypocenter: 72 who were exposed within 1999 m (closest group), 368 from 2000 to 5999 m (intermediate distant group), and 44 outside 6000 m (distant group). The positivity rates for AMA in these three groups were 6/72 (8.3%), 22/368 (6.0%), and 0/44 (0%), respectively (P =.08). Furthermore, high titers ( > 1:320) of AMA were observed in 3/6 (50%) AMA-positive sera from the closest group, in contrast to 4/22 (18%) from the intermediate distant group, although there was no significant correlation between AMA titer and distance from the hypocenter (P =.07). Of these 28 AMA-positive sera, 11 (39%) were from participants who had already been diagnosed with PBC, and 25 (89%) contained antibodies against at least one component of 2-OADC enzymes by immunoblotting. Therefore, the prevalence of PBC was estimated to be at least 615 cases per million (792 per million women). Our results suggest that the prevalence of PBC in atomic bomb survivors in Nagasaki is higher than that reported for the general population in Japan, and a further survey of the environmental factors, including radiation exposure, that predispose to PBC would be needed for understanding this disease of unknown etiology.
Asunto(s)
Cirrosis Hepática Biliar/epidemiología , Guerra Nuclear , Sobrevivientes , Anciano , Anciano de 80 o más Años , Fosfatasa Alcalina/sangre , Relación Dosis-Respuesta en la Radiación , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Japón/epidemiología , Cirrosis Hepática Biliar/etiología , Masculino , PrevalenciaRESUMEN
Deficiency of micronutrients, especially selenium, is common in critically ill patients. We investigated the micronutrient status (selenium, zinc, copper and manganese) and glutathione peroxidase (GSH-Px) activity in 30 tube-fed patients and 21 hospitalized non-tube-fed control patients. Serum levels of selenium, copper and manganese in tube-fed patients were significantly lower than in control patients (selenium: 4.85+/-1.38 microg/dl versus 8.67+/-1.45 pg/dl; copper: 44.7+/-36.9 microg/dl versus 92.1+/-21.2 microg/dl; manganese 0.59+/-0.41 microg/dl versus 1.52+/-0.59 microg/dl). However, zinc and log GSH-Px in the serum were similar in the two groups. Serum selenium concentration correlated with the daily intake of selenium in tube-fed patients, but zinc, copper and manganese concentrations did not correlate with the daily intake of the respective trace elements in tube-fed patients. Blood GSH-Px activity correlated positively with serum selenium concentrations in the control patients, but not in tube-fed patients. These results demonstrate that selenium content of enteral feed appears to be insufficient to maintain normal serum levels in elderly bedridden patients. Our findings emphasize the importance of monitoring micronutrient status in patients on enteral feeding to avoid trace element deficiencies.
Asunto(s)
Enfermedades Carenciales/sangre , Nutrición Enteral , Glutatión Peroxidasa/sangre , Estado Nutricional , Anciano , Anciano de 80 o más Años , Cobre/sangre , Cobre/deficiencia , Enfermedades Carenciales/enzimología , Femenino , Humanos , Masculino , Manganeso/sangre , Manganeso/deficiencia , Persona de Mediana Edad , Selenio/sangre , Selenio/deficiencia , Zinc/sangre , Zinc/deficienciaRESUMEN
We conducted a phase I study of irinotecan (CPT-11) and cisplatin with concurrent split-course radiotherapy in locally advanced stage III non-small cell lung cancer (NSCLC). This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of this therapy. Two chemotherapy cycles of CPT-11 (days 1, 8 and 15) and cisplatin (day 1) were repeated with a 28-day interval. Radiotherapy of 2 Gy/day commenced on day 2 of each chemotherapy cycle, with 24 Gy and 36 Gy administered for the first and second cycle, respectively. 24 eligible patients were enrolled at five dose levels (CPT-11/cisplatin: 40/60, 50/60, 60/60, 60/70 and 60/80 mg/m(2)), and 23 patients were evaluated for toxicity and clinical outcome. Only 1 patient experienced a DLT with neutropenia and diarrhoea at 60/60 mg/m(2). Dose escalation was limited to 60/80 mg/m(2) which was the recommended dose for CPT-11/cisplatin alone in NSCLC. Tumour responses included one complete response (CR), 15 partial response (PR), and 7 no change (NC), and the overall response rate was 69.6% (95% confidence interval (CI) 47.1-86.8%). This combined modality is tolerable, and CPT-11/cisplatin of 60/80 mg/m(2) in this modality is recommended for phase II study.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Terapia Combinada/métodos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Animal studies suggest that the kidney is involved in the elimination of recombinant human granulocyte colony-stimulating factor (rhG-CSF), which is used for patients with neutropenia during cancer chemotherapy. Since anticancer drugs induce nephrotoxicity, it is important to clarify the role of the kidney in the pharmacokinetics of rhG-CSF in cancer patients. Our study was designed to evaluate the relationship between the pharmacokinetics of rhG-CSF and renal function in lung cancer patients compared to the absolute neutrophil count (ANC). The pharmacokinetic studies were conducted with 25 lung cancer patients. Following chemotherapy using platinum-based compounds, a bolus 5 microg of rhG-CSF/kg of body weight was intravenously injected from the first day of leukopenia or neutropenia. Pharmacokinetic parameters were estimated by fitting the concentration in serum-time data to a two-compartment model according to the population pharmacokinetics and the Bayesian method. Creatinine clearance (CL(CR)) was predicted by the Cockcroft-Gault formula. rhG-CSF clearance (CL(G-CSF)) correlated significantly with the ANC (r = 0.613; P < 0.001) and CL(CR) (r = 0.632; P < 0.001). Multiple linear regression analysis showed that the combination of the ANC and CL(CR) accounted for 57.4% of the variation of CL(G-CSF). In patients with an ANC of <1,000/microl, CL(CR) accounted for 72.9% of the variation of CL(G-CSF) (P < 0.001). Our findings suggest that renal function and neutrophil counts correlate with CL(G-CSF) and that the role of renal function in eliminating rhG-CSF is important in lung cancer patients with neutropenia.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/farmacocinética , Riñón/metabolismo , Neoplasias Pulmonares/metabolismo , Adulto , Anciano , Femenino , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Proteínas Recombinantes/farmacocinéticaRESUMEN
We present two cases in which a soft-tissue sarcoma metastasized to the pancreas, but both patients survived as a result of repetitive surgical treatment during a 6- to 10-year period. The first case was a 29-year-old man who had a history of removal of mesenchymal chondrosarcoma in the left thigh in 1986 and who underwent distal pancreatectomy and the enucleation of a tumor in the head of the pancreas because of the development of three metastatic lesions in 1989. Afterward, although metastases were found in other organs, they were resected each time (for a total of five times) and the patient has survived over 10 years. The second case was a 40-year-old woman who had a history of the removal of synovial sarcoma in the right thigh and had 6 surgical resections of local or pulmonary recurrent tumors. She underwent pylorus-preserving pancreaticoduodenectomy in 1993 because of the development of a solitary metastatic lesion in the pancreas and survived more than 6 years after the pancreatectomy. Our report suggests, in selected cases, that long-term survival from pancreatic metastasis of soft-tissue sarcoma is expected as a result of curative resection. However, because pancreatic metastasis has a potential to recur in other organs, it is necessary to take aggressive surgical procedures repeatedly for the treatment of recurrences to improve prognosis after pancreatectomy.
Asunto(s)
Condrosarcoma Mesenquimal/secundario , Condrosarcoma Mesenquimal/cirugía , Neoplasias Pancreáticas/secundario , Neoplasias Pancreáticas/cirugía , Sarcoma Sinovial/secundario , Sarcoma Sinovial/cirugía , Neoplasias de los Tejidos Blandos/patología , Adulto , Femenino , Humanos , Masculino , Pancreatectomía , MusloRESUMEN
Heat shock protein Hsp40 is a stress protein with chaperone activity and has a cooperative function with Hsp70 in mammalian cells. We examined the possible expression of Hsp40 in lung tumor tissues using immunoblotting and immunohistochemistry, and established an enzyme-linked immunosorbent assay (ELISA) method to detect IgG antibody to Hsp40 in the serum using purified human Hsp40. Sera were obtained from 130 normal subjects and 50 patients with lung cancer. Lung tumor tissues and cells specifically overexpressed Hsp40, and no such expression was detected in normal lung tissues. Compared with normal sera, significantly higher levels of autoantibody to Hsp40 were present in patients with lung cancer. The present study is the first to demonstrate overexpression of Hsp40 in human tumor tissue and the associated presence of autoantibody to Hsp40 in the serum. These results suggest that overexpression of Hsp40 in tumor cells may be recognized as a self-antigen.
Asunto(s)
Autoanticuerpos/sangre , Proteínas de Choque Térmico/análisis , Proteínas de Choque Térmico/inmunología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Adenocarcinoma/patología , Carcinoma de Células Pequeñas/patología , Carcinoma de Células Escamosas/patología , Ensayo de Inmunoadsorción Enzimática , Proteínas del Choque Térmico HSP40 , Humanos , Inmunoglobulina G/sangre , Inmunohistoquímica , Pulmón/inmunología , Pulmón/patología , Neoplasias Pulmonares/sangre , Valores de ReferenciaRESUMEN
Breast cancer resistance protein (BCRP), an ABC half-transporter, is overexpressed in cancer cell lines selected with doxorubicin/verapamil, topotecan, or mitoxantrone. BCRP-overexpressing cells show cross-resistance to camptothecin derivatives such as irinotecan, SN-38 (the active metabolite of irinotecan), and topotecan. To test whether BCRP confers SN-38 resistance, we selected two SN-38 resistant sublines from PC-6 human small-cell lung cancer cells by SN-38, and then characterized these cells. Compared to PC-6 cells, the resistant sublines PC-6/SN2-5 and PC-6/SN2-5H were approximately 18- and 34-fold resistant, respectively. The intracellular SN-38 accumulation was reduced in the sublines, and BCRP mRNA was overexpressed in proportion to the degree of SN-38 resistance. These findings suggest that BCRP confers SN-38 resistance in the sublines. To confirm this hypothesis, PC-6/SN2-5 cells were transfected with antisense oligonucleotides complementary to portions of BCRP mRNA. The antisense oligonucleotides significantly suppressed BCRP mRNA expression, and enhanced SN-38 sensitivity in the subline. These data indicate that BCRP is directly involved with SN-38 resistance, by efflux transport of SN-38.