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11.
Correlation of drug sensitivity in vitro with clinical responses in childhood acute myeloid leukemia 总被引:1,自引:0,他引:1
Clonogenic cells from 41 children with newly diagnosed acute myeloid leukemia (AML) were tested in vitro for their sensitivity to cytarabine (Ara-C) and daunorubicin (DNR). The findings were then compared with the patients' responses to induction chemotherapy that uniformly included Ara-C and DNR. Light-density marrow cells were incubated with either or both drugs for one hour and cultured over leukocyte feeder layers; clusters and colonies were scored on days 7, 10, and 14. Only the percentage of cell kill in the presence of 1.8 mumol/L DNR was significantly associated with responses to induction therapy: median of 45% (range, 0% to 98%) for patients achieving complete remission v 16% (range, 4% to 23%) for nonresponders (P = .007). The relationship between clonogenic cell kill less than or equal to 23% and clinical responses was striking. Of the 11 evaluable patients with in vitro findings in this category, ten either failed induction therapy or relapsed within 1 year after attaining remission. Kaplan-Meier analysis of relapse-free survival times indicated longer durations of remission for patients whose blast cells showed increased sensitivity in vitro to Ara-C alone, DNR alone, or a combination of the two agents. Seven of 11 patients with cell kills of greater than or equal to 49% in the presence of 1.25 mumol/L Ara-C remain free of leukemia, compared with only one of 12 whose cells were less sensitive to the drug (P = .006). We conclude that the in vitro sensitivity of clonogenic leukemic progenitors to DNR and Ara-C correlates with treatment outcome in children with newly diagnosed AML. 相似文献
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Pruritus in hepatic cholestasis has been suggested to be secondary to a high concentration of serum bile acids. Rifampicin, which inhibits the uptake of bile acids by hepatocytes, has been used to treat pruritus. To determine the efficacy of rifampicin as a treatment for refractory pruritus, the medical records of 33 children (median age 25 months, range 4-135; 19 boys) with chronic cholestasis liver disease (21 with Alagille's syndrome, eight with progressive intrahepatic cholestasis, one with extrahepatic biliary atresia, one with an inborn error of bile acid metabolism, and one with cryptogenic cirrhosis) were reviewed retrospectively. The median dose of rifampicin was 5(4-10) mg/kg/day. The median duration of intake was 36(4-120) weeks. Complete relief of pruritus was noted in five (15%) patients and a partial response in 12 (36%). Overall, no significant difference was noted in the laboratory parameters before and after treatment with rifampicin. In the 21 patients with Alagille's syndrome, however, a significant decrease in alkaline phosphatase was seen before and after one and six months of starting treatment. No adverse side effects were seen. Rifampicin appears to be effective in the treatment of refractory pruritus. A prospective study is warranted to assess further the effect of rifampicin treatment in children with hepatic cholestasis. 相似文献
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Luciene G Mota Luiz GV Coelho Carlos JR Simal Maria LA Ferrari Clodomiro Toledo Josep Martin-Comin Simone OF Diniz Valbert N Cardoso 《World journal of gastroenterology : WJG》2010,16(3):365-371
AIM: To evaluate inflammatory activity in patients with Crohn’s disease (CD) using technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) granulocyte scintigraphy.METHODS: Twenty patients (7 male and 13 female) with CD and five healthy volunteers were selected for 99mTc-HMPAO granulocyte scintigraphy. The Crohn’s Disease Activity Index (CDAI), blood tests and C-reactive protein (CRP) of each patient were performed 7 d before the scintigraphic images. The leukocytes were labeled according to the International Society of Radiolabeled Blood Elements (ISORBE) consensus protocol and the scintigraphic images, including single photon emission computed tomography, were obtained 30 min and 2 h after injection of the radiolabeled leukocytes.RESULTS: The labeling yield of the leukocytes with the lipophilic complex 99mTc-HMPAO was 55.0% ± 10%. Six of the 20 patients (30%) presented congruent results for the three parameters investigated (CDAI, Scintigraphic Index and CRP). On the other hand, 14 patients (70%) did not show congruent results. There was no significant correlation between the indices analyzed according to the Spearman test (P > 0.05, n = 20).CONCLUSION: The results suggest that 99mTc-HMPAO-labeled leukocyte scintigraphy could be important for determining inflammatory activity in CD even in the absence of clinical symptoms. 相似文献
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Transforming growth factor beta 1 directly and reversibly inhibits the initial cell divisions of long-term repopulating hematopoietic stem cells 总被引:4,自引:3,他引:4
Hematopoiesis appears to be regulated, in part, by a balance between extracellular positive and negative growth signals. Transforming growth factor beta-1 (TGF-beta 1) has been shown to be a negative regulator of primitive hematopoietic cells. This study examined the direct effect of TGF-beta 1 on the proliferation and differentiation of long-term repopulating hematopoietic stem cells (LTR-HSC) in vitro. We previously reported a cell fractionation approach that includes the selection of low Hoescht 33342/low Rhodamine 123 (low Ho/Rh) cell fractions that are highly enriched for long-term repopulating cells (LTR-HSC) and also clone to a very high efficiency in the presence of stem cell factor (SCF) + interleukin-3 (IL-3) + IL-6: 90% to 100% of individually cultured low Ho/Rh cells formed high proliferative potential clones. This high cloning efficiency of an LTR-HSC enriched cell population enabled proliferation inhibition studies to be more easily interpreted. In this report, we show that the continuous presence of TGF-beta 1 directly inhibits the cell division of essentially all low Ho/Rh cells (in a dose-dependent manner) during their 0 to 5th cell division in vitro. Therefore, it follows that TGF-beta 1 must directly inhibit the proliferation of LTR-HSC contained within these low Ho/Rh cells. The time required for some low Ho/Rh cells to undergo their first cell division in vitro was also prolonged in the presence of TGF-beta 1. Furthermore, when low Ho/Rh cells were exposed to TFG-beta 1 for varying lengths of time before neutralization of the TGF-beta 1 by monoclonal antibody, the ability to form macroclones was markedly decreased after approximately 4 days of TGF-beta 1 exposure. In addition, 1 to 10 ng/mL of TGF-beta 1 resulted in a maintenance of high proliferative potential-colony-forming cell (HPP-CFC) during 8 days of culture compared with loss of HPP-CFC in cultures with no added TGF- beta 1. In conclusion, this study shows that TGF-beta 1 directly inhibits the initial stages of proliferation of LTR-HSC and appears to slow the differentiation of daughter cells of low Ho/Rh cells. 相似文献
17.
V Manchev JL Bruce GV Oosthuizen GL Laing DL Clarke 《Annals of the Royal College of Surgeons of England》2015,97(4):274-278
Introduction
The Pietermaritzburg Metropolitan Trauma Service (PMTS) has run a systematic quality improvement programme since 2006. A key component included the development and implementation of an effective surveillance system in the form of an electronic surgical registry (ESR). This study used data from the ESR to review the incidence, spectrum and outcome of paediatric trauma in Pietermaritzburg, South Africa.Methods
The ESR was reviewed, and all cases of paediatric trauma managed between 1 January 2012 and 30 July 2014 were retrieved for analysis.Results
During the study period, 1,041 paediatric trauma patients (724 male, 69.5%) were managed by the PMTS, averaging a monthly admission of 36. The mean age was 10.9 years (standard deviation: 5.4 years). The mechanism of injury (MOI) was blunt trauma in 753 patients (72.3%) and penetrating trauma in 170 (16.3%). Pedestrian vehicle collisions accounted for 21% of cases and motor vehicle collisions for a further 11%. Intentional trauma accounted for 282 patients (27.1%) and self-inflicted trauma for 14 cases (1.3%). Ninety patients admitted to the intensive care unit and fifty-one required high dependency unit admission. There were 17 deaths, equating to an in-hospital mortality rate of 1.7%. A total of 172 children died on the scene of an incident. There were 35 road traffic related deaths, 26 suicides by hanging, 27 deaths from blunt assault and 23 deaths from penetrating assault. The overall mortality rate for paediatric trauma was 18.2%.Conclusions
The ESR has proved to be an effective surveillance system and has enabled the accurate quantification of the burden of paediatric trauma in Pietermaritzburg. This has improved our understanding of the mechanisms and patterns of injury, and has identified a high incidence of intentional and penetrating trauma as well as road traffic collisions. These data can be used to guide strategies to reduce the burden of paediatric trauma in our environment. 相似文献18.
Release of galactosyltransferase from human platelets and a subset of monocytes in culture 总被引:1,自引:0,他引:1
We show that human monocytes and platelets release considerable amounts of galactosyltransferase (GT) in serum-free culture as measured by the amount of incorporation of 3H-galactose into ovalbumin. Enzyme production was the greatest among medium-sized mononuclear cells separated by counter-current elutriation. The cells were adherent and positive for the monocyte-specific monoclonal antibody FMC-32. The activity in the monocyte fractions was not due to platelet contamination as shown from experiments in which platelets or platelet antigens were eliminated. Cell viability decreased by less than 3% during the overnight culture, and results from cell disruption experiments showed that the enzyme was not released from dead or dying cells. Cycloheximide inhibited release during 20 hours culture. Approximately 50% of the enzyme in the cell culture supernatant was pelletable at 105,000 g. Platelets released the enzyme more rapidly than did monocytes and were readily stimulated by thrombin to release more GT. Thrombin also increased monocyte GT activity after overnight incubation, but other stimulants, zymosan and lipopolysaccharide (LPS), decreased release. We conclude that GT is released into culture supernatants by platelets and by a subset of peripheral blood monocytes. These sources may account for a significant proportion of the serum enzyme and may be important in modification of extracellular carbohydrates during inflammation and coagulation. 相似文献
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