Relapse after autologous bone marrow transplantation for chronic myelogenous leukemia (CML) can be due either to the persistence of leukemia cells in systemic tissues following preparative therapy, or due to the persistence of leukemia cells in the autologous marrow used to restore marrow function after intensive therapy. To help distinguish between these two possible causes of relapse, we used safety-modified retroviruses, which contain the bacterial resistance gene NEO, to mark autologous marrow cells that had been collected from patients early in the phase of hematopoietic recovery after in vivo chemotherapy. The cells were then subjected to ex vivo CD34 selection following collection and 30% of the bone marrow were exposed to a safety-modified virus. This marrow was infused after delivery of systemic therapy, which consisted of total body irradiation (1,020 cGy), cyclophosphamide (120 mg/kg), and VP-16 (750 mg/m2). RT PCR assays specific for the bacterial NEO mRNA, which was coded for by the virus, and the bcr-abl mRNA showed that in two evaluable CML patients transplanted with marked cells, sufficient numbers of leukemia cells remained in the infused marrow to contribute to systemic relapse. In addition, both normal and leukemic cells positive for the retroviral transgenome persisted in the systemic circulation of the patients for at least 280 days posttransplant showing that the infused marrow was responsible for the return of hematopoiesis following the preparative therapy. This observation shows that it is possible to use a replication-incompetent safety-modified retrovirus in order to introduce DNA sequences into the hematopoietic cells of patients undergoing autologous bone marrow transplantation. Moreover, this data suggested that additional fractionation procedures will be necessary to reduce the probability of relapse after bone marrow transplantation in at least the advanced stages of the disease in CML patients undergoing autologous bone marrow transplantation procedures. 相似文献
Objectives. We studied the duration and prognostic significance of atrial arrhythmias in the denervated transplanted heart, specifically the occurrence of atrial fibrillation in the absence of vagal modulation.
Background. Substantial animal data indicate that vagally induced dispersion of atrial refractoriness plays a central role in the induction and maintenance of atrial fibrillation.
Methods. We studied the occurrence of atrial arrhythmias in the denervated hearts of 88 consecutive orthotopic transplantations in 85 patients by means of continuous telemetry and all available electrocardiographic tracings.
Results. Fifty percent of recipients (44 of 88) developed at least one atrial arrhythmia. Atrial fibrillation occurred 23 times (21 recipients), atrial flutter 39 times (26 recipients), ectopic atrial tachycardia 3 times (3 recipients) and supraventricular tachycardia 18 times (11 recipients). The number of atrial fibrillation and atrial flutter episodes did not differ (23 vs. 39, p = 0.072), but the fibrillation (37.0 ± 10 vs. 6.6 ± 3.6 h, p = 0.014). Atrial fibrillation was associated with an increased risk of subsequent death (10 of 21 recipients with vs. 15 of 67 without atrial fibrillation, risk ratio 3.15 ± 0.18, p = 0.005 by Cox proportional hazards model). All 5 recipients who developed “late” atrial fibrillation (>2 weeks after transplantation) died versus 5 of 16 who developed atrial fibrillation within the first 2 weeks (p = 0.007). Causes of death included rejection (three recipients), allograft failure (two recipients), infection (three recipients) and multiorgan failure (two recipients). Atrial fibrillation was not associated with age, gender, ischemic time, reason for transplantation, echocardiographic variables, invasive hemodynamic variables or biopsy grade. Mean time from atrial arrhythmia to echocardiography was 2.7 ± 3.3 days; that to biopsy was 4.8 ± 6.3 days. Atrial flutter was not associated with subsequent death. Only 7 (15.9%) of 44 recipients demonstrated moderate or severe allograft rejection at the time of the arrhythmia.
Conclusions. Atrial arrhythmias occur frequently in the denervated transplanted heart, often in the absence of significant rejection. Late atrial fibrillation may be associated with an increased all-cause mortality. 相似文献
In a recent issue of Critical Care, Brandt and colleagues report the effects of a 'liberal' fluid loading protocol compared to a more 'restrictive' protocol
on hemodynamics and mortality in pigs in which septic shock had been induced. It appears that the former protocol was associated
with higher mortality in spite of improved hemodynamics compared to the latter. The results of the paper are discussed here
in view of the scope and mechanisms of these findings. With regard to fluid resuscitation, they indicate that too much of
an otherwise good thing is harmful, even if overhydration and edema formation seem to have been prevented. They also do not
exclude a specific toxic effect of the larger volumes of hydroxyethyl starch in the 'liberal' strategy. The precise nature
of a toxic effect remains obscure, however, but may involve the kidneys. 相似文献
Background Post‐inflammatory hyperpigmentation (PIH) is a common occurrence in patients with acne vulgaris, particularly in those with skin of colour. Aims A previous study has demonstrated the benefit of tretinoin (retinoic acid) in the treatment of PIH; however, there is currently no standard protocol to evaluate change in PIH following treatment. Based on these findings, we performed a pilot, exploratory, blinded, intraindividual‐controlled methodology study that consisted of a photographic assessment protocol with facial mapping. Materials and methods The study was based on a secondary analysis of a phase 4, community‐based trial of 544 acne patients who were treated with tretinoin gel microsphere 0.04% or 0.1%. Only patients with Fitzpatrick types III–V (skin of colour) were included in the study; subjects with Fitzpatrick skin type VI were excluded because the photographic assessment did not allow for proper evaluation. Results Despite the small number of subjects evaluated (n = 25), the results revealed consistent assessment of improvement in PIH between two independent graders (weighted κ = 0.84). Conclusion Further study with a larger population is recommended to validate the accuracy of this method. 相似文献