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61.
Weisdorf DJ; Verfaillie CM; Davies SM; Filipovich AH; Wagner JE Jr; Miller JS; Burroughs J; Ramsay NK; Kersey JH; McGlave PB 《Blood》1995,85(12):3452-3456
Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
62.
Thrombopoietin (c-Mpl ligand) has recently been purified and is considered to be the humoral regulator of platelet production. To see whether this molecule possessed the physiologic characteristics necessary to mediate the feed-back loop between blood platelets and the bone marrow megakaryocytes, we determined the relationship between blood levels of thrombopoietin and changes in the circulating platelet mass. We developed a model of nonimmune thrombocytopenia in rabbits by the subcutaneous administration of busulfan. Compared with pretreatment plasma, plasma taken from all thrombocytopenic rabbits at their platelet nadir contained increased amounts of thrombopoietin. All of this activity was neutralized by soluble c-Mpl receptor. We subsequently measured the level of thrombopoietin in the circulation over the entire time course after the administration of busulfan. As the platelet mass declined, levels of thrombopoietin increased inversely and proportionally and peaked during the platelet nadir. With return of the platelet mass toward normal, thrombopoietin levels decreased accordingly. When platelets were transfused into thrombocytopenic rabbits near the time of their platelet count nadir, the elevated levels of thrombopoietin decreased. In addition, platelets were observed to remove thrombopoietin from thrombocytopenic plasma in vitro. These results confirm that thrombopoietin is the humoral mediator of megakaryocytopoiesis and suggest that the platelet mass may directly play a role in regulating the circulating levels of this factor. 相似文献
63.
Detection of anti-HTLV-I Tax antibodies in HTLV-I enzyme-linked immunosorbent assay-negative individuals 总被引:10,自引:0,他引:10
Ehrlich GD; Glaser JB; Abbott MA; Slamon DJ; Keith D; Sliwkowski M; Brandis J; Keitelman E; Teramoto Y; Papsidero L 《Blood》1989,74(3):1066-1072
The HTLV-I tax gene protein (Tax) is not packaged within the mature viral particle from which the proteins for the commercially available enzyme-linked immunosorbent assay (ELISA) are derived. Screening of 162 individuals within a cohort of white intravenous (IV) drug abusers, previously identified as having an increased incidence of HTLV-I infection, demonstrated that seven of them had antibodies to the HTLV-I Tax protein but tested negative in HTLV-I ELISAs and Western blots prepared from purified virion proteins. Three out of 35 individuals in other behaviorally defined high-risk groups also displayed this limited pattern of reactivity to HTLV-I proteins. The presence of the anti-HTLV- I p40/Tax antibodies was determined by radioimmunoprecipitation assay (RIPA), which also revealed low levels of anti-env reactivity. The specificity of the anti-p40 reactivity was confirmed on specific Tax ELISAs and Western blots prepared from recombinantly produced Tax. In vitro gene amplification by the polymerase chain reaction (PCR) was used to establish the presence of sequences homologous to HTLV-I proviral DNA in four/four of these HTLV-I ELISA negative, Tax ELISA/Tax western blot/RIPA positive individuals. These data suggest that the true incidence of HTLV-I infection within high-risk cohorts is greater than previously reported. 相似文献
64.
Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia 总被引:4,自引:0,他引:4
Foon KA; Schroff RW; Bunn PA; Mayer D; Abrams PG; Fer M; Ochs J; Bottino GC; Sherwin SA; Carlo DJ 《Blood》1984,64(5):1085-1093
A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B- derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody. 相似文献
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EG Burden RW Walker DJ Ferguson AMF Goubran JR Howell JB John F Khan JS McGrath JP Evans 《Annals of the Royal College of Surgeons of England》2021,103(3):173
IntroductionWith the emergence of the COVID-19 pandemic, all elective surgery was temporarily suspended in the UK, allowing for diversion of resource to manage the anticipated surge of critically unwell patients. Continuing to deliver time-critical surgical care is important to avoid excess morbidity and mortality from pathologies unrelated to COVID-19. We describe the implementation and short-term surgical outcomes from a system to deliver time-critical elective surgical care to patients during the COVID-19 pandemic.Materials and methodsA protocol for the prioritisation and safe delivery of time-critical surgery at a COVID-19 ‘clean’ site was implemented at the Nuffield Health Exeter Hospital, an independent sector hospital in the southwest of England. Outcomes to 30 days postoperatively were recorded, including unplanned admissions after daycase surgery, readmissions and complications, as well as the incidence of perioperative COVID-19 infection in patients and staff.ResultsA total of 128 surgical procedures were performed during a 31-day period by a range of specialties including breast, plastics, urology, gynaecology, vascular and cardiology. There was one unplanned admission and and two readmissions. Six complications were identified, and all were Clavien-Dindo grade 1 or 2. All 128 patients had preoperative COVID-19 swabs, one of which was positive and the patient had their surgery delayed. Ten patients were tested for COVID-19 postoperatively, with none testing positive.ConclusionThis study has demonstrated the implementation of a safe system for delivery of time-critical elective surgical care at a COVID-19 clean site. Other healthcare providers may benefit from implementation of similar methodology as hospitals plan to restart elective surgery. 相似文献
69.
R Bahl DJ Murphy B Strachan 《BJOG : an international journal of obstetrics and gynaecology》2009,116(2):319-326
Objectives The objectives of this study were to define the components of a skilled low-cavity non-rotational vacuum delivery (occiput anterior, vertex at station +2 or below and less than 45-degree rotation from midline) and to facilitate the transfer of skills from expert to trainee obstetricians.
Design Qualitative study using interviews and video recordings.
Setting Two university teaching hospitals (St Michael's Hospital, Bristol, and Ninewell's Hospital, Dundee).
Participants Ten obstetricians and eight midwives identified as experts in conducting or supporting operative vaginal deliveries.
Methods Semi-structured interviews were carried out using routine clinical scenarios. The experts were also video recorded conducting low-cavity vacuum deliveries in a simulation setting. The interviews and video recordings were transcribed verbatim and analysed using thematic coding. The anonymised data were independently coded by three researchers and compared for consistency of interpretation. The experts reviewed the coded interviews and video data for respondent validation and clarification. The themes that emerged following the final coding were used to formulate a list of skills.
Main outcome measures Key technical skills of a low-cavity non-rotational delivery.
Results The final list included detailed technical skills required for conducting a low-cavity vacuum delivery. The combination of semi-structured interviews and simulation videos allowed the formulation of a comprehensive skills tool for future evaluation.
Conclusion This explicitly defined skills list could aid trainees understanding of the technique of low-cavity vacuum delivery. This is an important first step in evaluating clinical competence in intrapartum procedures. 相似文献
Design Qualitative study using interviews and video recordings.
Setting Two university teaching hospitals (St Michael's Hospital, Bristol, and Ninewell's Hospital, Dundee).
Participants Ten obstetricians and eight midwives identified as experts in conducting or supporting operative vaginal deliveries.
Methods Semi-structured interviews were carried out using routine clinical scenarios. The experts were also video recorded conducting low-cavity vacuum deliveries in a simulation setting. The interviews and video recordings were transcribed verbatim and analysed using thematic coding. The anonymised data were independently coded by three researchers and compared for consistency of interpretation. The experts reviewed the coded interviews and video data for respondent validation and clarification. The themes that emerged following the final coding were used to formulate a list of skills.
Main outcome measures Key technical skills of a low-cavity non-rotational delivery.
Results The final list included detailed technical skills required for conducting a low-cavity vacuum delivery. The combination of semi-structured interviews and simulation videos allowed the formulation of a comprehensive skills tool for future evaluation.
Conclusion This explicitly defined skills list could aid trainees understanding of the technique of low-cavity vacuum delivery. This is an important first step in evaluating clinical competence in intrapartum procedures. 相似文献
70.