ABSTRACT
Patients with amyotrophic lateral sclerosis (ALS) experience progressive and irreversible paralysis as a result of the continued loss of motor neurons, which leads to death in less than five years. To date, there is no treatment that can change the progression of this disease. Bone marrow stem cells have shown neural regenerative and neural repairing properties. Specifically, our group showed in a murine model of the disease that these cells, when injected in the spinal cord, can rescue motor neurons through the secretion of GDNF. Based on these results, we designed a phase I/II clinical trial for the purpose of demonstrating the viability of the intraspinal injection of autologous bone marrow mononuclear cells in patients with bulbar onset ALS, with an evolution between 6 and 36 months, with a forced vital capacity (FVC) 50% and T90 29%. This article describes the technique for extracting 60 mL of bone marrow used for the intervention, processing it by density gradient, and the neurosurgical technique used for implanting it. After 6 months of follow-up, the few adverse events reported in the first seven patients included seem to show that the procedure is safe and viable. Most of these patients, including two with a rapid deterioration, have stabilized the progression of their FVC and the neurologic scales measured. The data obtained so for seem to justify the design of new trials more oriented toward the efficacy of the procedure.
Subject(s)
Amyotrophic Lateral Sclerosis/surgery , Bone Marrow Transplantation , Motor Neurons/pathology , Nerve Degeneration , Nerve Regeneration , Amyotrophic Lateral Sclerosis/pathology , Amyotrophic Lateral Sclerosis/physiopathology , Animals , Bone Marrow Transplantation/adverse effects , Bone Marrow Transplantation/methods , Centrifugation, Density Gradient , Disease Progression , Humans , Injections, Spinal , Mice , Time Factors , Transplantation, Autologous , Treatment Outcome , Vital CapacityABSTRACT
AIM: To examine the use of extra-hospital emergency systems in the urgent care of stroke patients in our region and their influence on the time required to reach hospital, the time needed to perform an urgent computerised axial tomography (CAT) scan and the delay in receiving attention from the specialist. PATIENTS AND METHODS: Samples were collected from 232 stroke patients out of the total number admitted to our hospitals. Data about the stroke were collected prospectively, and included the arrival time, the time required to perform the CAT scan and the time the specialist devoted to attending the patient. Data were also gathered about the different extra-hospital transport and emergency systems. A statistical analysis was performed to determine the effect of using the extra-hospital emergency procedures on the different variables. RESULTS: A total of 53.6% of patients arrived within the first three hours. 38.7% went straight to hospital, 25% visited extra-hospital Emergency Services first, and 18.5% made a prior visit to Primary Care. 51.5% found their own way to the hospital and 46.7% arrived by ambulance. Mean time taken to perform an urgent CAT scan: 190.4 minutes; mean time required for specialist attention: 25.65 hours. The only statistically significant relation was the use of extra-hospital emergency systems and health care transport according to the type of stroke: both were more likely to be used in cases of haemorrhagic stroke. CONCLUSIONS: In hospitals in the Murcia region, the use of the extra-hospital emergency system and the means of transport utilised do not affect the time stroke patients take to reach hospital or the time needed to perform an urgent CAT scan or the delay in receiving attention from a specialist; the aetiology of the stroke does, however, influence the use of such services.
Subject(s)
Emergency Medical Services , Emergency Service, Hospital , Stroke , Hospitalization , Humans , Patient Admission , Prognosis , Prospective Studies , Stroke/diagnosis , Stroke/pathology , Stroke/physiopathology , Stroke/therapy , Time Factors , Tomography, X-Ray Computed , Transportation of Patients , Treatment OutcomeABSTRACT
Objetivo. Utilización en nuestra región de los sistemas de urgencias extrahospitalarias en la atención urgente del ictus y su influencia en el tiempo de llegada al hospital, el de realización de la tomografía axial computarizada (TAC) urgente y demora de la atención por el especialista. Pacientes y métodos. Se recogieron muestras de 232 pacientes con ictus del total de los ingresados en nuestros hospitales. Prospectivamente se recogieron datos sobre el ictus, con inclusión de los tiempos de llegada, tiempo de realización de la TAC y tiempo de atención por el especialista. Se recogió el uso delos distintos sistemas de urgencias y transporte extrahospitalarios. Estadísticamente se analizó la influencia del uso de los dispositivos de urgencia extrahospitalarios en las distintas variables recogidas. Resultados. 53,6% de los pacientes llegaron en las tres primeras horas. 38,7% acudieron directamente al hospital, el 25% acude primero al Servicio de Urgencias extrahospitalarias y 18,5% consulta previamente con Asistencia Primaria. El 51,5% llegaron por sus propios medios y el 46,7% en ambulancia. Tiempo medio de TAC urgente: 190,4 minutos; tiempo medio de atención por el especialista:25,65 horas. La única relación estadísticamente significativa fue el uso del sistema de urgencias extrahospitalarias y transporte sanitario según el tipo de ictus, con más tendencia a utilizarlos en los ictus hemorrágicos. Conclusiones. En los hospitales de Murcia, el uso del sistema de urgencias extrahospitalarias y el medio de transporte empleado no influyen en el tiempo de llegada del ictus al hospital, en el tiempo de realización de TAC urgente ni en la demora de atención por el especialista, y sí influye en la utilización de dichos servicios la etiología del ictus (AU)
Aim. To examine the use of extra-hospital emergency systems in the urgent care of stroke patients in our region and their influence on the time required to reach hospital, the time needed to perform an urgent computerised axial tomography(CAT) scan and the delay in receiving attention from the specialist. Patients and methods. Samples were collected from 232stroke patients out of the total number admitted to our hospitals. Data about the stroke were collected prospectively, and included the arrival time, the time required to perform the CAT scan and the time the specialist devoted to attending the patient. Data were also gathered about the different extra-hospital transport and emergency systems. A statistical analysis was performed to determine the effect of using the extra-hospital emergency procedures on the different variables. Results. A total of 53.6% of patients arrived within the first three hours. 38.7% went straight to hospital, 25% visited extra-hospital Emergency Services first, and 18.5% made a prior visit to Primary Care. 51.5% found their own way to the hospital and 46.7% arrived by ambulance. Mean time taken to perform an urgent CAT scan: 190.4 minutes; mean time required for specialist attention: 25.65hours. The only statistically significant relation was the use of extra-hospital emergency systems and health care transport according to the type of stroke: both were more likely to be used in cases of haemorrhagic stroke. Conclusions. In hospitals in the Murcia region, the use of the extra-hospital emergency system and the means of transport utilised do not affect the time stroke patients take to reach hospital or the time needed to perform an urgent CAT scan or the delay in receiving attention from a specialist; the aetiology of the stroke does, however, influence the use of such services (AU)
Subject(s)
Humans , Stroke/diagnosis , Stroke/pathology , Stroke/physiopathology , Stroke/therapy , Emergency Medical Services , Emergency Service, Hospital , Hospitalization , Patient Admission , Prognosis , Prospective Studies , Time Factors , Tomography, X-Ray Computed , Transportation of Patients , Treatment OutcomeABSTRACT
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been widely used after autologous peripheral blood stem cell transplant (APBSCT) in an attempt to reduce the duration of neutropenia, but whether this treatment has any influence on long-term engraftment remains unknown. We have retrospectively analyzed data from breast cancer patients to compare post-APBSCT rhG-CSF administration in terms of the short-term benefit and myeloid marrow regeneration after 1 year. Group A included 10 patients not treated with post-APBSCT rhG-CSF, while groups B and C comprised 15 and 13 patients treated with this drug from days +1 and +6, respectively. No differences among the three groups were found in age, diagnosis, previous chemo-radiotherapy, CD34+/CD71- cell concentration in pre-transplant bone marrow (BM), mobilization schedule, CD34+ cell yield, conditioning regimen and post-transplant radiotherapy. Post-APBSCT rhG-CSF was shown to accelerate neutrophil recovery, but there were no significant differences in platelet recovery, transfusion requirements, days of fever, antibiotic administration or inhospital stay. With regard to BM hematopoietic precursors 1 year after APBSCT, significantly lower concentrations of total CD34+ cells, committed CD34+/CD33+ subsets, and more immature CD34+/CD71- cells were found in both groups B and C compared with patients not having received the cytokine (group A). Thus, post-APBSCT rhG-CSF administration does not appear to beneficially affect procedure outcome, and might even impair long-term marrow hematopoiesis.
Subject(s)
Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Transplantation , Myeloid Progenitor Cells/drug effects , Adult , Antigens, CD/analysis , Bone Marrow Cells/cytology , Bone Marrow Cells/drug effects , Breast Neoplasms/therapy , Cell Count , Female , Follow-Up Studies , Graft Survival/drug effects , Granulocyte Colony-Stimulating Factor/pharmacology , Hematopoietic Stem Cell Transplantation/methods , Humans , Middle Aged , Recombinant Proteins , Retrospective Studies , Transplantation, Autologous/methodsABSTRACT
We assessed the mobilization capacity of taxol with rhG-CSF, both as a single chemotherapeutic agent and in the presence of cyclophosphamide (CY), and compared the effect with yields achieved when mobilization was performed solely with rhG-CSF. Fifteen patients with breast cancer received taxol 170 mg/m2 (continuous infusion, day 1) and rhG-CSF (8 microg/kg/day, from day 2 until the end of apheresis) (T-G group), while seven breast cancer patients were additionally treated with CY (4 g/m2) on day 2, followed by rhG-CSF starting at similar doses on day 3 (T-CY-G group). The PBSC collections after taxol with/without CY were compared with those of 30 breast cancer patients who had received rhG-CSF (8 microg/kg/day) for mobilization. No differences were found in the characteristics of patients included in any of the three mobilization groups. The median yield of CD34+ cells from all patients included in taxol containing schedules was 9 x 106/kg (range 2-26) collected with a median of one apheresis procedure (range 1-4). Leukaphereses began earlier in the T-G group (median day 8, range 7-10) than in the T-CY-G group (median day 13, range 11-17). In most patients (20 out of 22) who received taxol containing regimens, more than 2.5 x 106 CD34+ cells/kg, a threshold considered to be sufficient for hematopoietic reconstitution, were collected with a single apheresis. Those patients in the T-G group experienced less neutropenic and thrombocytopenic days, with all neutropenic fever episodes developing in patients treated with the T-CY-G schedule (43%). When considering priming with rhG-CSF alone in our historical cohort of 30 breast cancer patients, a significant detrimental effect was observed in comparison with taxol mobilizing schedules, in the number of aphereses performed, in the total yield CD34+cells and in the number of patients who achieved the target dose of 2.5 x 106/kg CD34+ cells within the first collection procedure. We conclude that taxol containing schedules are effective in mobilizing PBSC and facilitate the collection of high yields of CD34+ cells (usually more than 5 x 106/kg recipient body weight) with a reduced number of apheresis procedures. Taxol, as a single agent with rhG-CSF, exhibits less hematological toxicity than the combination chemotherapy mobilization regimen including CY. Bone Marrow Transplantation (2000) 25, 231-235.
