Marrow transplantation for chronic myelocytic leukemia: a controlled trial of cyclosporine versus methotrexate for prophylaxis of graft- versus-host disease

Forty-eight patients with chronic myelocytic leukemia, aged 11 to 47, were treated with high-dose cyclophosphamide and fractionated total body irradiation, followed by infusion of marrow from HLA-identical siblings. They were randomized to receive either methotrexate (MTX) (n = 23) or cyclosporine (CSP) (n = 25) as postgrafting prophylaxis for graft-v-host disease (GVHD). All patients had evidence of sustained hematopoietic engraftment. Seventeen of the 25 patients receiving CSP and 17 of the 23 patients receiving MTX are alive between one and almost four (median, 1.7) years, with an actuarial survival rate at three years of 62% and 66%, respectively (P = .60). Also, with respect to most other parameters studied, the two drugs were identical. The probability of acute GVHD was .42 and .46, respectively (P = .70), that of chronic GVHD, .50 and .63 (P = .44), and that of death from transplant-related causes, .30 and .24 (P = .51). There were no differences in the speed of granulocyte and platelet engraftment (P = .82 and .94, respectively), and the duration of hospitalization was comparable (P = .58). Patients receiving MTX required red cell transfusions for a shorter period of time (P = .02), but had a slightly increased morbidity from early oral mucositis. The leukemia recurrence rates were comparable (P = .60). With the regimens used in this study, we conclude that CSP failed to reduce the incidence of GVHD and improve the survival of patients with chronic myelocytic leukemia when compared to results with standard MTX.     

Unrelated donor or autologous marrow transplantation for treatment of acute leukemia

High-dose chemoradiotherapy followed by marrow transplantation from an HLA-matched sibling donor is curative for patients with acute leukemia. Autologous marrow transplantation has been used with success for some patients without such a sibling. Alternatively, the option of performing a transplant from an HLA-matched unrelated donor has been made possible by the recent development of large registries of HLA- typed volunteers. The purpose of this study was to compare the outcomes for patients with advanced leukemia treated by unrelated or autologous marrow transplantation. Forty-three patients with acute myeloid or lymphoid leukemia were transplanted from a closely HLA-matched unrelated donor. Results were compared with those of a disease-, disease-stage-, and age-matched cohort of 77 patients treated with autologous marrow transplantation at the same institution during the same period. Myeloid reconstitution with peripheral granulocyte counts greater than 10(9)/L was achieved in 93% of unrelated recipients and 70% of autologous recipients at a median of 24 and 36 days after transplantation, respectively (P = .0001). The cumulative proportions of patients discharged alive (79% v 77%) and times from transplant to first hospital discharge (35 v 34 days) were not different between unrelated and autologous recipients (P = .65). For patients transplanted in complete remission, relapse occurred after transplantation in 27% of the unrelated and in 55% of the autologous recipients (P = .08). For patients transplanted in relapse, the corresponding posttransplant relapse rates were 48% and 63%, respectively (P = .72). Forty percent of unrelated recipients and 28% of autologous recipients died in remission. Leukemia-free survivals were 33% for unrelated and 25% for autologous recipients transplanted in remission (P = .45), and 12% for unrelated and 5% for autologous recipients transplanted in relapse (P = .75). Unrelated donor transplants appear no less effective than autologous transplants to achieve long-term survival and may be more effective in eradicating leukemia in patients who have failed conventional chemotherapy. Further studies are warranted to assess the relative effectiveness of unrelated and autologous transplantation performed earlier in the course of the disease.     

Furosemide inhibits regenerative cortical spreading depression in anaesthetized cats

Ionic perturbations occur during cortical spreading depression (SD), a phenomenon implicated in migraine pathophysiology. We studied the effect of 0.2,2 and 20 mg kg⁻¹ iv ( n =4) furosemide on cortical direct current (d.c.) potential, cerebrovascular laser Doppler flux (rCBF_LDF), artery diameter and NO concentration in the parietal cortex of the anaesthetized cat during repetitive SD. In vehicle treated animals ( n =4), SD activity was sustained for 50 1.8 min. However, duration of SD activity was significantly reduced when compared to vehicle to 39 6.6 ( n =4), 3.1 8.3 ( n =4) and 27.3 11.3 min ( n =4), at 0.2, 2 and 20 mg kg⁻¹ iv furosemide respectively. It is hypothesized that the mechanism of inhibition of SD d.c. activity by furosemide may be through alterations in cortica ion buffering capacity or inhibition of cell swelling in neurones or glia. These mechanisms may represent potential novel drug targets in future migraine therapy.     

Density gradient separation of peripheral blood stem cells: comparison of an automated cell processing device and manual methods

Peripheral blood stem cells were collected from normal donors by leukapheresis on a cell separator. The leukapheresis product contained 1.5 x 10(10) mononuclear cells (MNCs) and was divided into two aliquots that underwent either automated or manual density gradient separation with ficoll-hypaque and subsequent washing. In the automated process, recovery of MNCs was 85 percent, reduction in platelet content was 64 percent, and the final hematocrit (Hct) was less than 1 percent. The manual separation resulted in 76-percent MNC recovery, a 79-percent reduction in platelet content, and a final Hct of less than 1 percent. The purified MNCs were then placed in methylcellulose culture at a concentration of 4 x 10(5) MNCs per mL. Quadruplicate 1-mL aliquots were cultured, and colonies were counted and classified on Day 14. Comparison of automated and manual ficoll-hypaque separations demonstrated no differences in the total, erythroid, or granulocyte-macrophage colony numbers. The cell processor used is fast, reliable, uncomplicated, and provides a sterile product containing progenitor cells that are not adversely affected by the automated ficoll-hypaque separation.     

基于MRI和血流动力学仿真的主动脉缩窄计算机辅助诊断系统

目前用于心脑血管系统疾病的计算机辅助诊断系统比较少，本研究基于参加欧盟FP7 euHeart项目所做的工作，以对主动脉缩窄的处理为例，介绍一个基于核磁共振成像（MRI）和血流动力学计算的心脑血管疾病计算机辅助诊断系统，对系统的结构、功能和工作流程进行详细描述。该系统以患者病变血管的MRI图像和在颈动脉和股动脉处测得的血压波形为输入信息，通过图像处理模块、生理数据处理模块、计算网格生成模块以及流体动力学计算模块对这些数据进行分析处理，输出跨缩窄段的压差以辅助评估对患者进行干预手术的必要性，并输出病变血管段的流速分布、剪切应力分布等血流状态信息用于估算血流异常对血管内皮以及血细胞造成潜在机械损伤的程度。以一个典型病例的处理结果为例，对所开发的系统进行初步测试，结果表明所开发的系统运行结果准确可靠。本系统对于开发其他心脑血管疾病计算机辅助诊断系统具有借鉴意义。     

Birth equity on the front lines: Impact of a community-based doula program in Brooklyn,NY

Background

We assessed whether participation in Healthy Start Brooklyn's By My Side Birth Support Program—a maternal-health program providing community-based doula support during pregnancy, labor and delivery, and the early postpartum period—was associated with improved birth outcomes. By My Side takes a strength-based approach that aligns with the doula principles of respecting the client's autonomy, providing culturally appropriate care without judgment or conditions, and promoting informed decision making.

Methods

Using a matched cohort design, birth certificate records for By My Side participants from 2010 through 2017 (n = 603) were each matched to three controls who also lived in the program area (n = 1809). Controls were matched on maternal age, race/ethnicity, education level, and trimester of prenatal-care initiation, using the simple random sampling method. The sample was restricted to singleton births. The odds of preterm birth, low birthweight, and cesarean birth were estimated, using conditional logistic regression.

Results

By My Side participants had lower odds of having a preterm birth (5.6% vs 11.9%, P < .0001) or a low-birthweight baby (5.8% vs 9.7%, P = .0031) than controls. There was no statistically significant difference in the odds of cesarean delivery.

Conclusion

Participation in the By My Side Birth Support Program was associated with lower odds of preterm birth and low birthweight for participants, who were predominantly Black and Hispanic. Investing in doula services is an important way to address birth inequities among higher risk populations such as birthing people of color and those living in poverty. It could also help shape a new vision of the maternal-health system, placing the needs and well-being of birthing people at the center.